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Tarja Lyytinen Physical Function and Biomechanics of Gait in Obese Adults after Weight Loss Publications of the University of Eastern Finland Dissertations in Health Sciences TARJA LYYTINEN Physical Function and Biomechanics of Gait in Obese Adults after Weight Loss To be presented by permission of the Faculty of Health Sciences, University of Eastern Finland for public examination in Canthia auditorium L3, Kuopio, on Friday, October 2 nd 2015, at 12 noon Publications of the University of Eastern Finland Dissertations in Health Sciences Number 293 Department of Physical and Rehabilitation Medicine, Kuopio University Hospital Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences Department of Applied Physics and Mathematics University of Eastern Finland Kuopio 2015 Grano Oy Kuopio, 2015 Series Editors: Professor Veli-Matti Kosma, M.D., Ph.D. Institute of Clinical Medicine, Pathology Faculty of Health Sciences Professor Hannele Turunen, Ph.D. Department of Nursing Science Faculty of Health Sciences Professor Olli Gröhn, Ph.D. A.I. Virtanen Institute for Molecular Sciences Faculty of Health Sciences Professor Kai Kaarniranta, M.D., Ph.D. Institute of Clinical Medicine, Ophthalmology Faculty of Health Sciences Lecturer Veli-Pekka Ranta, Ph.D. (pharmacy) School of Pharmacy Faculty of Health Sciences Distributor University of Eastern Finland Kuopio Campus Library P.O.Box 1627 FI-70211 Kuopio, Finland http://www.uef.fi/kirjasto ISBN (print): 978-952-61-1840-6 ISBN (pdf): 978-952-61-1841-3 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L (print): 1798-5706 ISSN-L (pdf): 1798-5706 III Author’s address: Palokka Health Center Ritopohjantie 25 FI-40270 Palokka FINLAND E-mail: [email protected] Supervisors: Docent Jari Arokoski, M.D., Ph.D. Department of Physical and Rehabilitation Medicine Kuopio University Hospital Institute of Clinical Medicine School of Medicine Faculty of Health Sciences University of Eastern Finland Kuopio, Finland Tuomas Liikavainio, M.D., Ph.D. Lääkäriasema Terva Muonio, Finland Professor Pasi Karjalainen, Ph.D. Department of Applied Physics and Mathematics University of Eastern Finland Kuopio, Finland Reviewers: Professor Janne Avela, Ph.D. Neuromuscular Research Center Department of Biology of Physical Activity University of Jyväskylä Jyväskylä, Finland Docent Jari Parkkari, M.D., Ph.D. UKK Institute Tampere, Finland Opponent: Docent Maunu Nissinen, M.D., Ph.D. Department of Physical and Rehabilitation Medicine Helsinki University Hospital Helsinki, Finland IV V Lyytinen, Tarja Physical Function and Biomechanics of Gait in Obese Adults after Weight Loss Publications of the University of Eastern Finland Dissertations in Health Sciences. 293. 2015. 124 p. ISBN (print): 978-952-61-1840-6 ISBN (pdf): 978-952-61-1841-3 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L (print): 1798-5706 ISSN-L (pdf): 1798-5706 ABSTRACT Obesity is associated with several musculoskeletal disorders such as the development and progression of knee osteoarthritis (OA). Thus, impaired physical function, impaired health sense, muscle strength and body balance and differences in gait biomechanics have all been observed in obese subjects and in knee OA subjects. The present series of studies was designed to examine how body mass index (BMI), bariatric surgery and subsequent weight loss could affect gait biomechanics, physical function, the structure of quadriceps femoris muscle (QFm) and the subjective disabilities of subjects with excessive weight. Special emphasis was placed on investigating both objectively and subjectively measured physical function with a test battery of physical function tests and questionnaires (RAND-36 and WOMAC). The properties of the QFm were evaluated with ultrasound and the skin mounted accelerometers (SMAs) and ground reaction forces were used to estimate knee impact loading during walking. The repeatability of SMAs in combination with simultaneous surface electromyography (EMG) measurements of lower extremities and standing balance in healthy subjects and knee OA patients was also examined. The overweight and obese subjects loaded their lower extremity more than lean individuals during level walking. Weight loss after bariatric surgery decreased impulsive knee joint loading during walking, inducing a simple mass-related adaptation in gait and also accomplishing a degree of mechanical plasticity in gait strategy. The weight loss occurring after bariatric surgery exerted a positive impact on physical function, reducing the subcutaneous fat thickness of the QFm and improving the subjects’ perception of their VI health status. However, major weight loss had a negative effect on the QFm muscle thickness and the CSA and the fat and connective tissue proportion of the QFm. SMA and EMG were revealed as being reproducible tools for evaluating joint impact loading and muscle activation of QFm during walking in healthy subjects, but not in knee OA subjects. Subjects with knee OA do not have a standing balance deficit, but they do exhibit increased muscle activity in QFm during standing in comparison to control subjects. National Library of Medicine Classification: WD 210, WI 900, WE 348 Medical Subject Headings: Obesity; Gait; Biomechanics; Physical function; Electromyography; Repeatability of Results; Osteoarthritis; Knee; Postural Stability VII Lyytinen, Tarja Ylipainoisten aikuisten toimintakyky ja kävelyn biomekaniikka painon pudotuksen jälkeen Itä-Suomen yliopisto, Terveystieteiden tiedekunta Publications of the University of Eastern Finland. Dissertations in Health Sciences. 293. 2015. 124 p ISBN (print): 978-952-61-1840-6 ISBN (pdf): 978-952-61-1841-3 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L (print): 1798-5706 ISSN-L (pdf): 1798-5706 TIIVISTELMÄ Ylipaino on yhteydessä useisiin tuki- ja liikuntaelinsairauksiin. Se on esimerkiksi merkittävä polvinivelrikon riskistekijä. Heikentynyt fyysinen toimintakyky, huonontunut elämänlaatu, alentunut lihasvoima ja huonontunut tasapaino sekä muutokset kävelyn biomekaniikassa on havaittu liittyvän sekä ylipainoon että polven nivelrikkoon. Tässä väitöstutkimuksessa selvitettiin painoindeksin ja laihdutusleikkauksen jälkeisen painonpudotuksen vaikutuksia kävelyn biomekaniikkaan ja terveydentilaan liittyvään elämänlaatuun. Lisäksi tutkimuskohteena olivat kyseiset vaikutukset subjektiivisesti koettuun ja objektiivisesti mitattuun suorituskykyyn sekä nelipäisen reisilihaksen rakenteeseen. Fyysistä suoristuskykyä mitattiin testipatteristolla ja subjektiivista toimintakykyä arvioitiin kyselykaavakkeilla (RAND-36 ja WOMAC). Nelipäisen reisilihaksen rakennetta tutkittiin ultraäänellä. Lisäksi selvitettiin iholle kiinnitettävien kiihtyvyysanturimittausten elektromyografiamittausten toistettavuutta ja ja alaraajan lihasten polvinivelrikon pinta vaikutusta seisomatasapainoon. Laihdutusleikkauksen jälkeinen painon pudotus alensi polviniveleen kohdistuvaa iskukuormitusta aikaansaaden sekä yksinkertaisen massaan suhteutetun että mekaanisen muuntumisen kävelytavassa. Ylipainoiset ja lihavat henkilöt kuormittivat enemmän alaraajojaan kävelyn aikana verrattuna normaalipainoisiin henkilöihin. Laihdutusleikkauksen jälkeinen painon pudotus paransi itsearvioitua ja objektiivisesti mitattua suorituskykyä sekä vähensi nelipäisen reisilihaksen ihonalaisen rasvakudoksen paksuutta. Samalla se kuitenkin pienensi nelipäisen reisilihaksen lihaspaksuutta ja VIII poikkipinta-alaa sekä vaikutti negatiivisesti lihaksen rasva-sidekudossuhteeseen. Kiihtyvyysanturi ja pinta elektromyografia osoittautuivat toistettaviksi menetelmiksi arvioitaessa polven nivelkuormitusta ja lihasten aktivoitumista tasamaakävelyn aikana terveillä koehenkilöillä. Kyseiset menetelmät eivät olleet kuitenkaan toistettavia polvinivelrikkopotilailla. Polvinivelrikolla ei havaittu olevan merkittävää vaikutusta seisomatasapainoon. Luokitus: WD 210, WI 900, WE 348 Yleinen Suomalainen asiasanasto (YSA): ylipaino, kävely, biomekaniikka, toimintakyky, lihakset, luotettavuus, nivelrikko, polvi, tasapaino IX Gutta cavat lapidem non vi, sed saepe cadendo: pertinacia vincit omnia. To Tuomas and Emilia I love you X XI Acknowledgements This thesis has been carried out in the Department of Physical and Rehabilitation medicine, Kuopio University Hospital and the Department of Applied Physics, University of Eastern Finland in 2008-2015. This study has been financially supported by EVO-grant (no: 5041705) and by Kärkihanke MSRC, project-grant (no: 931053) from Kuopio University Hospital and the North-Savo Fund of the Finnish Cultural Foundation which I acknowledge with deep gratitude. I want to express my warmest gratitude to my main supervisor Docent Jari Arokoski, M.D, Ph.D. I was fortunate to work with extraordinary bright and talented expert. He devoted remarkable amounts of time and energy to this project. I truly appreciate his time and engagement with this project. This thesis would not have been accomplished without expert advices and endless encouragement that he has given to me throughout these years and especially during the most challenging moments of this project. I thank him for our scientific and instructive discussions and discussions concerning everyday life. I admire his extensive expertise and wonderfully supportive attitude and respect his way to guide. His unconditioned support has carried me throughout this scientific journey. He always believed in me, also then when I have my weak moments during this process. It has been a great privilege to get to know him. I am also deeply grateful to my second supervisor Tuomas Liikavainio, M.D, Ph.D. He has participated strongly in this study with his ideas and comments on the writing and he has given to me a great possibility to use part of his dataset in my thesis. I thank him for our scientific and everyday life discussions, which were very fruitful and important to me. Tuomas and Jari always took care of me and their familiar greeting was always: “How are you, how is it really going in your life?” This was the most important things during this project. In addition, I am very grateful to my third supervisor Professor Pasi Karjalainen, Ph.D. for his wise and invaluable advices and comments concerning especially the mathematical part of this study. XII I am very grateful also to Timo Bragge, M.Sc., for his valuable support during data collection and analysis as well as in making figures of the original publications. We became friends during these years. I also wish to thank Marko Hakkarainen, M.Sc. and Paavo Vartiainen, M.Sc., for their support in data collection. They all have been always ready to accomplish study measurements at evenings and weekends. We have had some technical problems during the measurements but they have solved them graciously. I thank Timo, Marko and Paavo for that they have made it easy to me to adjust myself to their group in Centek as an only woman. I also want to thank Professor emerita Helena Gylling, M.D, Ph.D and Matti Pääkkönen M.D. for their contribution to this study. I express my sincere thanks to the reviewers of this thesis, Professor Janne Avela, Ph.D., and Docent Jari Parkkari, M.D., Ph.D., for their constructive comments and criticism, which have helped me to improve my thesis. I wish my best thanks to Ewen MacDonald, Ph.D. for revising the language of this thesis and part of the original publications and also Roy Siddal for revising the language of part of the original publications. I am grateful to Vesa Kiviniemi, Ph.L. and Tuomas Selander for their valuable help in the statistical analyses. I also thank Milla Tuulos, M.D. and Timo Räsänen, M.D. for their assistance during data collection. This thesis would not exist without all subjects who participated voluntarily in these experiments. I am very thankful to them for being involved. I also sincerely thank my work mates and associate chief physician Jyrki Suikkanen in Palokka Health Center for allowing me to do and finish this thesis. I am deeply grateful to my dear friends for all the memorable moments, valuable discussions in everyday life and support throughout these years. You know who I mean. I owe my deepest thanks to my parents Leena and Heikki for their endless love, encouragement and emotional support in my life. They have given to me and my siblings the most important keys of life, which carry us forward in our lives and help us to achieve our dreams and goals. My father has challenged me to achieve with his own incredible achievements. I love you both. I thank my dearest sister Anne and brother Tapio for their support and love. Our close band of siblings will last forever, I love you. I also thank my XIII sister’s and brother’s soulmates Tero and Mira and my dear godson Oliver for the joyful moments in everyday life. I am grateful to my deceased grandmother Helvi and my grandfather Pentti for their emotional support and love. I also express thanks to my second family for their warm support in everyday life. Finally I would be remiss if I didn’t acknowledge the importance of my family. My loving thanks belong to my soulmate and best friend Tuomas and my dear daughter Emilia for their endless and unselfish love. They have brought so much love and joy to my life and also kept me connected with everyday life. I am extremely grateful to Tuomas for his continuous patience, understanding and support he has given me throughout these years. I also thank him for his valuable help with figures and technical problems in this thesis. Emilia and Tuomas have reminded me every day about what are the most important and precious things in my life. Palokka, July 2015 Tarja Lyytinen XIV XV List of the original publications This dissertation is based on the following original publications: I. Lyytinen T, Bragge T, Liikavainio T, Vartiainen P, Karjalainen PA, Arokoski JPA. The impact of obesity and weight loss on gait in adults. In book: The Mechanobiology of Obesity and Related Diseases. Chapter 7: 125-147, 2014. II. Lyytinen T, Liikavainio T, Pääkkönen M, Gylling H, Arokoski JP. Physical function and properties of quadriceps femoris muscle after bariatric surgery and subsequent weight loss. Journal of Musculoskeletal & Neuronal Interactions 13 (3): 329- 38, 2013. III. Lyytinen T, Bragge T, Hakkarainen M, Liikavainio T, Karjalainen PA, Arokoski JPA. Repeatability of knee impulsive loading measurements with skin-mounted accelerometers and lower limb surface electromyographic recordings during gait in knee osteoarthritic and asymptomatic individuals. Submitted. IV. Bragge T*, Lyytinen T*, Hakkarainen M, Vartiainen P, Liikavainio T, Karjalainen PA, Arokoski JPA. Lower impulsive loadings following intensive weight loss after bariatric surgery in level and stair walking: a preliminary study. The Knee 21 (2): 534- 40, 2014. V. Lyytinen T, Liikavainio T, Bragge T, Hakkarainen M, Karjalainen PA, Arokoski JP. Postural control and thigh muscle activity in men with knee osteoarthritis. Journal of Electromyography and Kinesiology 20 (6): 1066- 74, 2010. *Equal Contributors XVI The publications were adapted with the permission of the copyright owners. XVII Contents 1 INTRODUCTION ......................................................................................................................... 1 2 REVIEW OF THE LITERATURE ................................................................................................ 3 2.1 Obesity in adults ...................................................................................................................... 3 2.1.1 Subjectively measured physical function and health related quality of life .................. 3 2.1.2 Objectively measured physical function .................................................................................................... 4 2.1.3 Treatment of obesity ................................................................................................................................................... 5 2.1.3.1 Effects of weight loss on physical function and health related quality of life .......................................................................................................................................................................................... 6 2.1.3.2 Effects of weight loss on body composition ..................................................................... 14 2.2 Pathogenesis of the knee osteoarthritis ................................................................................ 15 2.2.1 Pathophysiology ......................................................................................................................................................... 15 2.2.1.1 The role of muscles .............................................................................................................................. 16 2.2.2 Risk factors ...................................................................................................................................................................... 18 2.3 Diagnosis and treatment of knee osteoarthritis................................................................... 20 2.3.1 Symptoms ........................................................................................................................................................................ 20 2.3.2 Clinical findings .......................................................................................................................................................... 22 2.3.3 Radiological findings .............................................................................................................................................. 23 2.3.4 Criteria of diagnosis ................................................................................................................................................. 23 2.3.5 Treatment of knee osteoarthritis .................................................................................................................... 24 2.4 Normal gait cycle ................................................................................................................... 25 2.4.1 Gait phases ...................................................................................................................................................................... 25 2.4.2 Biomechanics of stair walking ......................................................................................................................... 28 2.4.3 Gait analysis ................................................................................................................................................................... 29 2.4.3.1 Accelerometers ........................................................................................................................................ 32 XVIII 2.4.3.2 Electromyographic measurements .......................................................................................... 32 2.5 Gait changes in obese subjects .............................................................................................. 33 2.5.1 Spatiotemporal variables ..................................................................................................................................... 33 2.5.2 Gait kinematics ............................................................................................................................................................ 34 2.5.3 Gait kinetics .................................................................................................................................................................... 34 2.6 Effects of weight loss on gait characteristics........................................................................ 36 2.6.1 Conservative weight loss interventions ................................................................................................... 36 2.6.2 Bariatric surgery .......................................................................................................................................................... 38 3 AIMS OF THE STUDY ............................................................................................................... 39 4 EXPERIMENTAL PROCEDURES............................................................................................. 40 4.1 Subjects and selection ............................................................................................................ 40 4.2 Experimental design .............................................................................................................. 42 4.2.1 Experiment 1 .................................................................................................................................................................. 42 4.2.2 Experiment 2 .................................................................................................................................................................. 43 4.2.3 Experiment 3 .................................................................................................................................................................. 43 4.3 Data recording and analysis ................................................................................................. 46 4.3.1 Questionnaires.............................................................................................................................................................. 46 4.3.2 Radiological measurements ............................................................................................................................... 46 4.3.3 Anthropometric measurements, knee and hip joint range of motion, knee muscle strength and blood biochemical measurements .......................................................................... 47 4.3.4 Acceleration measurements ............................................................................................................................... 48 4.3.5 Ground reaction force measurements ....................................................................................................... 49 4.3.6 Measurements of electromyography .......................................................................................................... 49 4.3.7 Postural stability measurements .................................................................................................................... 50 4.3.8 Physical function measurements ................................................................................................................... 51 4.3.9 Statistical analysis ...................................................................................................................................................... 52 XIX 5 RESULTS ...................................................................................................................................... 54 5.1 Characteristics of subjects ..................................................................................................... 54 5.2 Repeatability of measurements with skin mounted accelerometer and electromyorgaphy ........................................................................................................................ 58 5.2.1 Repeatability of acceleration measurements ........................................................................................ 58 5.2.2 Repeatability of electromyography measurements ........................................................................ 59 5.3 Effects of obesity and weight loss on joint loading ............................................................. 60 5.3.1 Ground reaction forces .......................................................................................................................................... 60 5.3.2 Accelerations .................................................................................................................................................................. 60 5.4 Effects of weight loss on physical function .......................................................................... 63 5.4.1 Questionnaires.............................................................................................................................................................. 63 5.4.2 Physical function tests ............................................................................................................................................ 65 5.4.3 Muscle composition ................................................................................................................................................. 66 5.5 Postural stability in knee osteoarthritis................................................................................ 68 5.5.1 Postural stability ......................................................................................................................................................... 68 5.5.2 Muscle activation during standing .............................................................................................................. 69 5.5.3 Postural stability correlations ........................................................................................................................... 73 6 MAIN FINDINGS AND DISCUSSION .................................................................................. 74 6.1 Study population ................................................................................................................... 74 6.2 Repeatability of acceleration and EMG measurements ...................................................... 75 6.3 Effects of obesity and weight loss on joint loading ............................................................. 80 6.4 Effects of weight loss on physical function and composition of QFm .............................. 83 6.5 Postural stability in knee osteoarthritis................................................................................ 85 6.6 Clinical implications for future studies ................................................................................ 87 7 CONCLUSION ............................................................................................................................ 91 8 REFERENCES .............................................................................................................................. 93 XX APPENDIX: ORIGINAL PUBLICATIONS (I-V) XXI Abbreviations AP Anterior-posterior az, r, xy Axial, resultant and horizontal IPA Initial peak acceleration resultant acceleration, kg Kilogram respectively K-L Kellgren-Lawrence coefficient ARD Average radial displacement osteoarthritis grading scale ATRmax Maximal acceleration transient (0-4) rate LR Loading rate BF Biceps femoris muscle MF Mean frequency BMI Body mass index ML Medial-lateral COP Centre of pressure MSV Mean sway velocity CSA Cross sectional area MIPC Mean of individual CV Coefficient of variation EA Elliptical area EMG Electromyography EMGact Electromyographic activity percentual changes MRI Magnetic resonance imaging OA Osteoarthritis PP Peak-to-peak antero-posterior, medio- PSD Power spectral density lateral and vertical QFm Quadriceps femoris muscle directions, respectively RAND-36 RAND 36-Item Health FAP, FML, FV Ground reaction forces in the fbalance Balance frequency fEMG EMG frequency RMS Root mean square GM Gastrocnemius medialis RF Rectus femoris muscle ROM Range of motion GRF Ground reaction force SD Standard deviation HRQOL Health Related Quality of SF Short form health survey Life SMA Skin mounted Hz Hertz, unit of frequency ICC Intra-class correlation Survey 1.0 accelerometer TA Tibialis anterior muscle XXII TUG Timed Up and Go VAAP Velocity along anteriorposterior axes VAML Velocity along mediallateral axes VAS Visual analog scale VL, VM Vastus medialis and lateralis of quadriceps femoris muscle WOMAC Western Ontario and McMaster Universities Arthritis Index XXIII 1 Introduction Obesity has become a major public health problem in both the developed and developing countries; in global terms it is the most prevalent chronic disorder. The World Health Organisation estimated in 2008 that more than 1.4 billion adults, 20 years and older, were overweight (body mass index (BMI) 25.0-29.9 kg/m2), and of these, about 200 million men and nearly 300 million women were obese (BMI ≥30.0 kg/m2) (1). In Finland, about 56% of the adult population is obese or overweight (2). Overweight and obesity are the leading risk factors for deaths all around the world, e.g. an elevated BMI is a major risk factor for diabetes, cardiovascular diseases, musculoskeletal disorders, especially osteoarthritis (OA) (1). Obesity has been found to be associated with impaired daily living physical activities, lower muscle strength and disturbed gait biomechanics (3-6). OA is the best known degenerative joint disease affecting articular cartilage and subchondral bone, resulting in a narrowing of the joint space and pain (7). Knee OA has been found to be related to impaired physical function, i.e. poorer muscle strength, joint range of motion (ROM) and poor postural balance (8-10). Obesity increases the risk of radiographic and symptomatic knee OA (11). The increased mechanical loading has been claimed to be the primary cause of knee OA disease progression (12). The surgical option for weight reduction i.e. bariatric surgery, has been proposed as an effective treatment, since it can achieve a long term weight loss (13), an improvement in comorbidities (14) and improvements in physical function and health-related quality of life (HRQOL) (15,16). The treatment of obesity is also highly recommendable in knee OA subjects, because weight loss decreases pain and improves joint function in these patients (17). It is thought that both the mechanical and biochemical profiles of obese adults can be changed as a consequence of the reduction in joint loadings (5,18). Earlier studies investiging the effects of weight loss on joint loading in obese subjects have mostly concentrated on assessing the actual joint moments by applying modern gait analysis 2 techniques (19-21). However, the assessment of impulsive joint loading during gait is not always possible with these gait analytical techniques. The skin mounted accelerometers (SMAs) have been shown to represent a convenient alternative for the evaluation of impulsive joint loading in the knee joint (22-25). The aim of the present series of studies was to review the effects of obesity and weight loss on gait biomechanics and to investigate the impact of BMI on knee impulsive joint loading. A further aim was to study how bariatric surgery and subsequent weight loss would alter physical function as well as the properties of quadriceps femoris muscle (QFm) and knee joint impact loading. One further goal was also to examine the repeatability of SMAs and electromyography (EMG) measurements of the lower extremities during walking and to evaluate postural balance together with QFm function in both healthy individuals and knee OA subjects. 3 2 Review of the Literature 2.1 OBESITY IN ADULTS Overweight and obesity are defined as abnormal or excessive amount of fat in the body (1). BMI is a useful and simple index, which has a clear connection to the amount of fat mass (26). Overweight (BMI 25 - 29.9 kg/m2) and obesity (BMI≥30 kg/m2) are caused by the energy imbalance between calories consumed and calories expended. The World Health Organisation reports that major changes have occurred in dietary and physical activity patterns such as an increased intake of energy-dense food and decrease in physical activity (1). Obese individuals have been found to have a significantly higher level of functional limitations and physical dysfunction than their normal-weight counterparts (27). 2.1.1 Subjectively measured physical function and health related quality of life Obesity has been shown to be associated with decreases in subjectively measured physical function and HRQOL. Müller-Nordhorn et al. (28) conducted a cross-sectional analysis and observed that BMI was inversely associated with physical HRQOL, as measured by the 12-Item Short Form (SF-12) health status instrument. The change in BMI was inversely related to physical HRQOL in women and in obese subjects in their longitudinal (over 3 years) analyses (28). Hergenroeder et al. (29) studied the effects of obesity on self-reported physical function by applying the Late Life Function and Disability Instrument in adult women. The obese and overweight individuals experienced a significant reduction in selfreported physical function when compared to normal-weight individuals (29). Bentley et al. (30) reported that six commonly used HRQOL indexes (physical and social functioning, role limitations, pain, mental health and vitality) revealed the presence of lower HRQOL in obese and overweight subjects in comparison with normal-weight individuals. They reported also that the association between obesity and HRQOL appeared to be driven 4 primarily by physical health (30). King et al. (31) studied self-reported walking capacity in obese and severely obese people and found that 7% of participants reported that they were unable to walk 200 feet (about 60 metres) unassisted, 16% mentioned at least some use of a walking aid, and 64% reported limitations in walking several blocks (31). Schoffman et al. (32) found that higher BMI was associated with certain aspects of HRQOL, including higher self-reported pain, fatigue, stiffness and disability. Those adults with higher BMI had statistically reduced physical HRQOL when compared to normal-weight adults. 2.1.2 Objectively measured physical function Obesity has also been found to be associated with impaired objectively measured physical function. Lang et al. (33) stated that excess body weight increased 27.4% (men) and 38.1% (women) the risk of impaired physical function in community-dwelling men and woman aged 65 and older. Sibella et al. (34) determined that obese subjects adopted a different movement strategy from non-obese subjects to complete a sit-to-stand task. The obese subjects’ forward trunk flexion was reduced and their feet were moved backwards from the initial position. They suggested that the reduction in trunk flexion represented an attempt to diminish loading of their lower back (34). Hergenroeder et al. (29) investigated the effects of obesity on physical function by using 6-minute walk, timed chair rise and gait speed tests in middle-aged women with different BMI categories. They observed that obese individuals walked 25.6% shorter distance in 6-minute walk test, spent 48.1% more time in timed chair rise test and had 28.1% lower gait speed compared to normal-weight individuals. They also found that overweight individuals experienced a significant reduction in physical function as compared to normal-weight individuals (29). King et al. (31) claimed that almost half of their obese subjects displayed a mobility deficit during 400 meter corridor walking and there was a clear association between the severity of obesity and increased walking limitations (31). Schoffman et al. (32) showed that BMI was highly associated with impaired physical function as measured by a variety of objective tests of 5 function (i.e. six-minute walk test, the 30-second chair stand and the seated reach tests). The shorter distances on the six-minute walk test, fewer stair stands and shorter seated reach were found in association with a higher BMI (32). Ling et al. (35) studied physical function in obese subjects by using the six-minute walk test and the Timed Up and Go (TUG) test; these workers detected significantly poorer physical function in obese individuals with BMI of 40 kg/m2 or more in comparison with overweight subjects with BMI between 26-35 kg/m2. One of the important causes of impaired physical function in obese individuals is believed to be reduced muscle strength (4) and lowered skeletal muscle mass (27,36). Stenholm et al. (4) reported that those older obese individuals with decreased lower limb muscle strength had a higher risk for the development of physical function disability compared with those without obesity and lower muscle strength. Zoico et al. (27) demonstrated that a low percentage of muscle mass significantly increased the probability of experiencing functional limitations (27). 2.1.3 Treatment of obesity There are three approaches to the treatment of obesity: lifestyle modification, pharmacotherapy, and bariatric surgery (Table 1). The optimal treatment approach is determined by the individual’s BMI and the presence or absence of comorbid conditions. Lifestyle modification, which includes diet, exercise, and behavior therapy, is suitable for individuals with BMI 25.0-26.9 kg/m2 in the absence of comorbid conditions. Individuals with BMI 27.0-34.9 kg/m2 who present with two or more/absence comorbid conditions profit most from the combination of lifestyle modification and pharmacotherapy. Subjects with BMI 35.0-39.9 kg/m2 with comorbid conditons and BMI ≥ 40 kg/m2 can be considered as candidates for surgical therapy (e.g. bariatric surgery) as a treatment to remove the excess weight (37). 6 Table 1. Treatment of obesity. BMI catecory (kg/m²) 25.0-26.9 27.0-34.9 Without comorbid conditions With comorbid conditions 35.0-39.9 ≥ 40 With comorbid conditions With/without comorbid conditions Treatment option Lifestyle modification (diet, exercise, behavior therapy) Pharmacotherapy Bariatric surgery With comorbid conditions The dietary component of lifestyle modification by itself (a 500 kcal/day deficit) has been shown to lose 8% of the body weight over a 6 month period. The physical activity itself could result in about 3 % body weight loss (37). The most effective approach to losing weight involves a combination of behavioral strategies and diet and exercise to achieve a sustained lifestyle change (38,39). In Finland, only one medication, orlistat, is available for the pharmacological treatment of obesity. The recommended guideline is that weight loss medication and lifestyle modification together should be used in the treatment of obesity (37). The surgical option, such as bariatric surgery (e.g. Roux-en-Y gastric bypass) is presently considered to be an efficacious and successful treatment since it achieves long term weight loss (13), an improvement in comorbidities (14) and better HRQOL (15,16). Bariatric surgery has been shown to produce sustainable and substantial weight loss, on average a 40 kg weight loss or 14 kg/m2 BMI decrease, in morbidly obese individuals (40). 2.1.3.1 Effects of weight loss on physical function and health related quality of life Weight loss is associated with increased mobility, improved physical function in addition to the other improvements in experienced HRQOL which have been reported after 7 conservative weight loss interventions (Table 2). Villareal et al. (41) investigated the effects of weight loss induced by either diet or exercise alone and in combination on subjectively and objectively measured physical function in obese adults after 6 and 12 months from the baseline measurements. There was a substantial decrease in body weight in the diet group (a 10% decrease from baseline) and in the diet–exercise group (a 9% decrease from baseline), but not in the exercise alone group or in the control group. Physical function as measured either objectively (e.g. walking 50 feet, putting on and removing a coat, picking up a penny, standing up from a chair) or subjectively (36-Item Short Form health status (SF-36)) increased significantly in the weight loss groups in comparison to the control group (41). The modified physical performance test scores increased 21%, 15% and 12% in the diet-exercise, exercise- and diet-groups (41). The functional status questionnaire scores increased 10% and 4% in the diet-exercise and diet groups (41). A randomized controlled trial study conducted by Beavers et al. investigated the effects of weight loss induced by three interventions (physical activity, weight loss plus physical activity and education) in obese adults (42). The overall loss of body weight was 7.84 kg after the weight loss intervention program. Significant improvements in self-reported physical function and 3.6% increase in walking speed (4-meter walk) were observed after weight loss (42). In a US study done in women, it was found that weight loss was associated with improved HRQOL in the physical functioning domain as evaluated by the SF-36 questionnaire (43). Napoli et al. (44) conducted a randomized controlled trial to determine the effects of weight loss and exercise on subjective physical function in obese older adults about one year after the weight loss intervention. They showed that total Impact of Weight on Quality of Life scores improved more in the diet, exercise and diet plus exercise groups with decreasing body weight when they were compared to the control group (44). HRQOL after bariatric surgery has been investigated using different questionnaires such as the SF-36 questionnaire (15). Tompkins et al. (45) showed that the scores on the physical component summary of SF-36 improved by 36.4% at 3-months and by 51.4% at 6months after surgery (45). Josbeno et al. (16) found that the physical function subscale of 8 the SF-36 and the total SF-36 had also improved significantly at three months after surgery. McLeod et al. (46) explored the impact of weight loss on HRQOL at six months after bariatric surgery and detected a significant improvement in the physical component summary scores of SF-36. Strain et al. (47) evaluated HRQOL at 25 months after bariatric surgery with four different procedures and demonstrated significantly improved HRQOL regardless of which surgical procedure had been performed (47). Efthymiou et al. (48) examined the effects of weight loss on HRQOL at 1 month, 6 months, and 1 year after bariatric surgery in obese women and found significantly reduced BMI and improvement in the physical component scores of SF-36 questionnaire during the first year postoperatively (48). A recent meta-analysis also demonstrated that one could expect a major improvement in HRQOL as measured with SF-36 questionnaire after the individual was subjected to bariatric surgery (49). Only a few studies have investigated the effects of bariatric surgery on objectively measured daily living physical activities (Table 2). Tompkins et al. (45) evaluated the effects of weight loss on physical function at three and six months after gastric bypass surgery in morbidly obese adults. They reported that the walking distance in the 6-minute walking test increased by 22% at 3-months and even more, by 33.2% at 6-months after surgery. The body weight had been reduced by 18.4% at 3-months and by 27.3% at 6months after surgery (45). Miller et al. (15) conducted a longitudinal and observational study to examine the impact of gastric bypass surgery on weight loss and physical function in morbidly obese subjects at twelve months after surgery. The twelve months’ weight loss was 34.2% and the physical performance tasks improved significantly after surgery. The authors detected a significant relationship between the amount of weight loss and the improvement in physical function, with greater weight loss achieving increased function after bariatric surgery (15). Josbeno et al. (16) observed that bariatric surgery, especially gastric bypass surgery, could improve physical function (Short Physical Performance Battery and the six-minute walk test) at three months after surgery. de Souza et al. (50) investigated the impact of weight loss on physical function as measured by the 6- 9 minute walk test in severely obese subjects at 7-12 months after bariatric surgery. The mean distance of the six-minute walk test increased by 22.5% when BMI decreased by 44.8% after surgery (50). 10 Table 2. Effects of weight loss on objectively and subjectively measured physical function and body composition in weight loss interventions. Author Number of subjects Study design Weight management Results Objectively measured physical function Miller et al. (2009) (15) 28 12-month longitudinal, observational study Bariatric surgery The Short Physical Performance Battery scores and the Fitness Arthritis and Seniors Trail questionnaire scores ↑ de Souza et al. (2009) (50) 49 7-12-month controlled trial Bariatric surgery The distance of 6minute walk test ↑ significantly Subjectively measured physical function McLeod et al. (2012) (46) 28 6-month controlled trial Bariatric surgery SF-36 scores in physical and mental components ↑ Pan et al. (2014) (43) 2 cohort studies, 121.7 subjects in the first study and 116.671 subjects in second study 8-year follow up study No any diet or exercise SF-36 scores in physical components ↑ when losing weight Napoli et al. (2014) (44) 107 1-year randomized controlled trial Diet, dietexercise, exercise IWQOL scores↑ in all three groups Strain et al. (2014) (47) 105 25-month controlled trial Bariatric surgery SF-36 scores in general health, physical and physical function components ↑, IWQOL scores in all components ↑ Efthymiou et al. (2014) (48) 80 1-year prospective controlled trial Bariatric surgery SF-36 scores in all aspects ↑ significantly Magallares et al. (2014) (49) 21 studies, 2251 subjects The meta-analysis, review study Bariatric surgery Significant ↑ in mental and physical components of the SF-36 11 Table 2. (continued) Objectively and subjectively measured physical function Tompkins et al. (2008) (45) 25 3- 6-month controlled trial Bariatric surgery 22% and 33.2% ↑ in walking distance at 3months and 6-months after surgery; the physical component summary of SF-36 ↑ 36.4% at 3-months and 51.4% at 6months after surgery Josbeno et al. (2010) (16) 20 3-month controlled trial Bariatric surgery The scores for 6minute walk test, Short Physical Performance Battery, physical function subscale of the SF-36 and the total SF-36 ↑ significantly Villareal et al. (2011) (41) 93 1-year randomized controlled trial diet, exercise, diet and exercise The Modified Physical Performance Test scores ↑ 21%, 15%, 12% in the dietexercise, exercise, diet groups Functional status questionnaire scores ↑ 10%, 4% in the diet-exercise, diet groups Beavers et al. (2013) (42) 271 A randomized controlled trial Physical activity, diet plus physical activity, a successful aging education control arm 3.6% ↑ in 4-meters walking speed, the scores for Pepper assessment tool for disability questionnaire ↑ 17 2-3 year controlled trial, using DEXA Bariatric surgery 21.8% ↓ in body weight, 30.1% ↓ in fat mass, 12.3% ↓ fat free mass Body composition Strauss et al. (2003) (55) 12 Table 2. (continued) Sergi et al. (2003) (56) 6 6-month controlled trial, using DEXA Bariatric surgery 16% ↓ in body weight, 14%↓ in fat free mass Giusti et al. (2004) (51) 31 A prospective study, using DEXA Bariatric surgery 23.3% ↓ in body weight, 36.8% ↓ in fat mass, 9.6% ↓ in fat free mass Carey et al. (2006) (54) 19 12-month controlled trial, using underwater weighing Bariatric surgery 36.2% ↓ in body weight, 75.2% ↓ in fat mass, 24.8% ↓ in lean mass Zalesin et al. (2010) (52) 32 12-month controlled trial, using DEXA Bariatric surgery 36.5% ↓ in body weight, fat mass ↓, lean mass ↓ Santanasto et al. (2011) (53) 36 6-month randomized controlled trial, using DEXA and computerized tomography A physical activity and diet, a physical activity and a successful aging health education program A body weight, thigh fat and muscle area ↓, thigh fat area ↓ 6fold vs. lean area Villareal et al. (2011) (41) 93 1-year randomized controlled trial Diet, exercise, diet and exercise 10%, 9%, 1%↓ in body weight in the diet, diet-exercise, exercise groups; 5%, 3% ↓ in lean body mass in diet and dietexercise groups; 17%, 16%, 5% ↓ in fat mass in diet, dietexercise, exercise groups Pereira et al. (2012) (59) 12 6-month prospective study, using ultrasound Bariatric surgery BMI ↓, fat mass ↓ in lower extremities, lean mass ↓ in lower extremities 13 Table 2. (continued) Beavers et al. (2013) (42) 271 A randomized controlled trial, using DEXA Physical activity, diet plus physical activity, a successful aging education program 8.5% ↓ in body weight, 15.1% ↓ in fat mass, 5.1% ↓ in lean mass SF-36, 36-Item Short-Form Health Survey; IWQOL, Impact of Weight on Quality of Life-Lite; DEXA, a dual-energy x-ray absorptiometry. 14 2.1.3.2 Effects of weight loss on body composition The rapid and massive weight loss occurring after bariatric surgery, but also after more conservative weight loss interventions, achieves not only a loss of the total body fat mass but also in the lean body mass according to dual energy X-ray absorbtiometry analysis (42,51-53) (Table 2). Similar results have also been found when the lean body mass has been estimated by magnetic resonance imaging (MRI) and underwater weighing (41,54). Giusti et al. (51) examined the effects of gastric banding on body composition one year after surgery in obese women. There was a 36.8% reduction of body fat mass and 9.6% reduction of lean mass seen after surgery and it was observed that lean tissue losses correlated directly with the rate of weight loss after bariatric surgery (51). Zalesin et al. (52) also noted that the patients who had undergone the greatest rate of weight loss after bariatric surgery, lost relatively more muscle mass as well as fat mass. However, it has also been reported that it is mainly fat loss which occurs with a relative preservation of lean mass (55,56). The less extensive and slower weight loss occurring after weight loss interventions in comparison to the severe weight loss induced by bariatric surgery have led to fat mass loss and lean mass loss. Beavers et al. (42) assessed the total body fat and lean mass with dual energy X-ray absorbtiometry analysis after a weight loss intervention in obese older adults. It was found that there were statistically significant 15% and 5.1% losses of both fat and lean mass occurring after the weight loss intervention. They also showed that the fat mass loss was a more significant predictor of the subsequent change in physical function than the lean mass loss. They concluded that improvement in physical function was associated with the amount of fat mass lost and was independent of the amount of lean mass lost (42). Santanasto et al. (53) reported that a physical activity plus weight loss intervention program significantly decreased both fat and muscle cross-sectional area (CSA). They demonstrated that fat mass decreased many times more than the corresponding muscle mass and that this more ideal fat-free mass to fat mass ratio resulted in improved physical function (53). It has been claimed that the loss of muscle 15 mass or lean mass would be accelerated by weight loss if not accompanied by physical activity in older adults (57). Villareal et al. (41) measured the effects of weight loss on thigh muscle and fat volumes by using MRI; it was found that there was a 5% and 3% decline in muscle mass and 17% and 16% decline in fat mass in diet and diet-exercise groups but an increase in the muscle mass in the exercise alone group (41). They concluded that adding an exercise program to diet may result in the preservation of muscle mass (41). Chomentowski et al. (58) concluded also that accelerated muscle loss could be lessened if accompanied by moderate aerobic exercise. Almost every study has concentrated on the effects of weight loss on the whole body composition and there is very little information about the impact of weight loss on fat mass and muscle structure in the lower extremities. Pereira et al. (59) used ultrasound techniques to investigate the thickness of the QFm as well as adjacent subcutaneous adipose tissue in obese patients at one month, three months and six months after bariatric surgery. They showed that the thickness of QFm mass and fat mass decreased significantly after the weight loss induced by surgery. Both the fat mass and muscle mass showed progressive reductions in their thickness in relation to the preoperative values (59). 2.2 PATHOGENESIS OF THE KNEE OSTEOARTHRITIS 2.2.1 Pathophysiology Although OA can mainly be considered as an impairment of articular cartilage such as the result of an imbalance between catabolic and anabolic activities in joint tissue (60) induced by biochemical, biomechanical, genetic and metabolic factors, it is also disease affecting the subchondral bone, synovium, capsule, periarticular muscles, sensory nerve endings, meniscus and supporting ligaments (61) (Figure 1). The degradation of the articular cartilage, thickening of the subchondral bone, the formation of osteophytes, variable 16 degrees of synovial inflammation, degeneration of ligaments and the menisci, loss of muscle strength, and hypertrophy of the joint capsule can all be seen as pathological changes in the joints of knee OA patients (62) (Figure 1). Figure 1. The pathophysiological changes occurred in knee OA. The healthy side on the left and the affected side on the right of the knee joint. 2.2.1.1 The role of muscles Muscle weakness, and especially QFm weakness, has been associated with knee OA (6367). Hortobagyi et al. (68) detected weakness in eccentric, concentric, and isometric quadriceps strength in knee OA patients. Serrao et al. (66) found a reduction only in eccentric knee strength in the knee OA patients and proposed that this deficit in eccentric knee strength could lead to a reduction in the normal shock absorbtion action of the joint, leading to advanced knee OA. Kumar et al. (67) reported lower QFm isometric strength and isokinetic strength in their knee OA group as compared to a control group. On the 17 contrary, Conroy et al. (69) found no differences in absolute QFm strength between subjects with and without knee OA. The mechanism behind the muscle weakness is not fully understood. The deficit in muscle strength has been suggested to be associated with muscle atrophy i.e. a reduction in the number of muscle fibers (70). Many sophisticated techniques, e.g. MRI, ultrasound, computed tomography and bio-impedance analysis techniques have been used to evaluate the muscle composition of knee OA patients. Visser et al. (71) showed that skeletal muscle mass was positively associated with clinical symptoms and structural properties in knee OA subjects (71). Kumar et al. (67) investigated the composition of QFm in knee OA patients and healthy controls using MRI. They found that the knee OA subjects had greater intramuscular fat fractions for QFm, but no differences in QFm CSA (67). Conroy et al. (69) noted that knee OA subjects had greater whole body lean and muscle tissue, greater QFm CSA as detected by computed tomography and lower QFm specific torque (strength/muscle CSA). Eckstein et al. (72) stated that reductions in QFm CSAs could be observed in OA knees in comparison to control knees when they used MRI in their evaluation. In addition, a lower muscle quality could be one possible explanation for muscle weakness in knee OA (66). There is evidence that also histopathological changes can be observed in periarticular muscles in knee OA. Fink et al. (70) detected atrophy of type two fibers (fast muscle fibers) in biopsy specimens from the patients with advanced knee OA. They also reported atrophy of slow-twitch type 1 fibers from 32% of the knee OA patients and additional fiber type groupings, suggestive of some kind of reinnervation, which they interpreted as being indicative of neurogenic muscular atrophy. They also postulated that atrophy of type 2 fibers might be involved in the pain-associated immobilization of knee OA patients (70). 18 2.2.2 Risk factors The OA risk factors can be divided into systemic, i.e. generalized constitutional factors (e.g. age, gender, genetics), and local biomechanical factors (e.g. joint injury, malalignment, muscle weakness, overweight/obesity). The most important risk factors for knee OA are ageing, obesity, joint injury and heavy physical occupation (Figure 2) (Table 3). Ageing is the most important risk factor for OA. The presence of OA in one or more joints increases from less than 5% at age between 15 and 44 years, to 25% to 30% at age from 45 to 64 years, and to more than 60% at age over 65 years (73,74). It has been proposed that the reduction of chondrocyte function related to age impairs these cells’ abilities to maintain and repair damaged articular cartilage (73). It has been reported that overweight and obesity increase the risk for knee OA (7577). There seems to be a statistically significant, nonlinear, dose-response association between BMI and the risk of knee OA (11,78). There are two primary mechanisms, biomechanical and metabolic, thought to be behind the processes linking obesity and knee OA (60,75,77). 19 Figure 2. The pathogenic factors for knee OA. Knee OA results from articular cartilage failure caused by abnormal stress to normal cartilage or abnormal cartilage with normal stress and leading to the degradation of the articular cartilage, subchondral bone and synovium (79). In the biomechanical perspective, the excessive body weight adds an excessive mechanical load on the knee and this can lead to pathological processes such as fibrillation and degradation of articular cartilage (75,78). From the metabolic view, a strong correlation has been found between knee OA and the highly inflammatory metabolic environment associated with obesity (60,75,77). 20 Table 3. Risk factors for knee OA (17). Risk factors Evidence References Age +++ Female gender +++ (80-82) (80,83) Genetic factors ++ (84-87) Knee malalignment ++ (18,88-90) Obesity +++ (11,91-93) Heavy physical occupation ++ (92,94-96) Heavy sport activity ++ (97-100) Knee injury +++ (80,92,101,102) Meniscectomy + (80,103,104) +++ convincing evidence, ++ moderate evidence, + weak evidence. A previous knee joint injury (e.g. anterior cruciate ligament rupture) is strong risk factor for knee OA (76,105). Occupations involving activities such as heavy lifting, squatting, kneeling, working in a cramped space, climbing stairs, floor activities, or higher physical demands increase the risk of suffering knee OA (76,106). It is difficult to draw clear conclusions about the association between sporting activities and knee OA because of the heterogeneous nature of the studies (76). Investigations into the association between malalignment and knee OA have also produced conflicting results (18,107-109), but there is strong evidence for an association between knee OA progression and malalignment (18). 2.3 DIAGNOSIS AND TREATMENT OF KNEE OSTEOARTHRITIS 2.3.1 Symptoms The presence of joint pain is the primary symptom of knee OA. In addition, OA patients experience brief morning stiffness, restriction ROM and impairment of functional ability. Individuals with knee OA have described the pain as either an intermittent pain or as a persistent background pain or aching (110). In the early stages of OA, the pain is said to be 21 a deep aching poorly localized discomfort that becomes worse during activity and is alleviated with a resting period (73,110). With the progression of the disease, the pain may become more constant and more severe or intense, occurring at rest or even at night and disturbing the sleep (73,110). The pain can also affect negatively on mood and participation in social and recreational activities (110). The most commonly used tool for the evaluation of subjective pain, is a visual analog scale (VAS) (110). The cause of pain in OA is not well understood. In a systematic review, 15-76% of those with knee pain had radiographic OA, and 15-81% of those with radiographic OA had knee pain (110). It has been postulated that some pathological processes may occur in different joint structures that have an effect on pain production in OA. The articular cartilage is aneural and avascular and is not capable of directly evoking pain symptoms in OA. However, there are rich sensory innervations in other joint tissues (111). Certain structural changes such as microfractures and osteophytes, stretching of the nerve endings in the periosteum, bone marrow lesions and oedema and intraosseus hypertension in bone and subchondral bone may be involved in the generation of the joint pain (111,112). In addition, during inflammation, many mediators are released into the joint and these can sensitize the primary afferent nerves and cause a painful response (111). Further, the psychological factors such as depression and anxiety, overweight via mechanical loading and fat mass via production of adipokines have been observed to be associated with pain in knee OA (110). The major clinical consequence of knee OA is physical disability, which means difficulty in performing daily activities such as walking, stair climbing, rising from a chair, transferring in and out of a car, lifting and carrying objects. The functional disability encountered in knee OA may involve knee pain, stiffness, duration of the disease and muscle weakness (113). In addition to obesity, laxity of the affected knee and the effect of comorbidity on HRQOL have been suggested to explain the disability in end-stage knee OA (114). The Western Ontario and McMaster Universities (WOMAC) OA index 22 questionaire is often used for evaluating the subjective physical functioning in OA patients (115). 2.3.2 Clinical findings The clinical inspection can reveal the changes in movements such as limping caused by joint pain, decreased walking speed, reduced stride length and frequency, changes in the position of the joint during standing, alterations in joint appearance and difficulties in squatting (17,116). In advanced stages of knee OA, the bony prominences caused by osteophytes, varus- and valgus malalignments, joint subluxation, deformity and oedema are typical findings (17,73). In addition, joint degradation can lead to detectable muscle atrophy (73). The local tenderness in knee joint can be probed with palpation of the knee joint. Furthermore, the amount of the joint fluid may increase because of episodic synovitis and this can cause palpable swelling, but no significant heat or redness. The audible and palpable crepitus is cracking or crunching over the knee joint during both active and passive joint movement. The reduced ROM can be measured with a goniometer (17). Several studies have reported that knee OA patients may have experience impaired proprioceptive accuracy for both position and motion senses (117). The possible mechanisms behind the impaired postural stability in knee OA are not fully understood, but the presence of pain (118-120), disease severity (8,119,120), and decreased muscle strength (119) have been postulated as contributing factors. Several clinical studies have detected a decrease in the QFm strength in patients with radiographic knee OA, whether symptomatic or not (63-66,121) and it has been suggested that changes in the neuromuscular properties of QFm can affect the postural balance in knee OA patients (119,122). Many different balance tests have been used in postural control studies to obtain relevant information of postural stability in knee OA patients when they are standing 23 (8,118-120,122-126). Laboratory tests do not have any significance in the diagnosis of knee OA, but they can be useful in the differential diagnosis (17). 2.3.3 Radiological findings The conventional radiography is the gold standard imaging technique for the evaluation of suspected knee OA and also for the evaluation of the severity of knee OA (17,127). Joint space narrowing, the presence of osteophytes, subchondral cystic areas with subchondral sclerosis, and bony deformities are typically seen in radiographic images in knee OA (127,128). Nonetheless, the subjective feelings of pain, self-reported disability and radiographic changes do not necessarily associate with each other (113,114,128). There are also other imaging methods such as MRI, ultrasound and computed tomography, but these are not routinely used in the clinical initial assessment of knee OA patients (127,128). There are several classification methods available for evaluating the severity of knee OA. The most often applied classification of knee OA is the Kellgren-Lawrence (K-L) (129) classification. In the K-L scale, 0 refers to no OA, grade 1 includes possible joint space narrowing and the presence of osteophytes, in grade 2 there is definite joint space narrowing and osteophytes, grade 3 refers to definite joint space narrowing, multiple osteophytes, sclerosis, cysts and possible deformity of the bone contour and grade 4 includes marked joint space narrowing, large osteophytes, severe sclerosis, cysts and definite deformity of bone contours. The repeatability of K-L grading in knee OA has been demonstrated as being good (130). 2.3.4 Criteria of diagnosis The diagnosis of knee OA can be based on radiological findings, clinical findings or a combination of these two approaches. The diagnosis of knee OA requires radiological findings such as joint space narrowing, the formation of osteophytes, and possible 24 indications of bone deformation. The combined radiographic and clinical criteria have been proposed as being more useful in the diagnostic evaluation of knee OA (17,131). This combination has been demonstrated to achieve 94% sensitivity and 88% specificity (131). 2.3.5 Treatment of knee osteoarthritis There is no cure for OA nor any treatment proven to prevent or slow OA progression. Thus, reducing joint pain and improving physical ability are the main goals in the treatment of OA (17). The current guidelines for the management of knee OA recommend the use of both non-pharmacological and pharmacological therapies such as the elimination of risk factors and physical therapy and analgesic treatment (Figure 3). The pharmaceutical treatment is important, but should not be used as the sole treatment strategy of knee OA (17,132,133). The other conservative treatment modalities of knee OA included self-management and education, weight management, biomechanical interventions and exercise training (17,132,133) (Figure 3). Surgical modalities may need to be considered when conservative treatment alone is not sufficient to control pain and disability of function, but conservative treatment methods are still utilized to reinforce the knee arthroplasty (17) (Figure 3). 25 Figure 3. Knee OA treatment options (17). 2.4 NORMAL GAIT CYCLE 2.4.1 Gait phases Gait cycle is determined as a series of repetitive patterns involving steps and strides. A stride, which is the distance between two consecutive contacts of the same foot, contains a whole gait cycle. The gait cycle is measure from heel contact of one limb to heel contact of the same limb (134). Each gait cycle is divided into stance and swing phases and lasts approximately one second depending on walking speed and gait pathologies (135) (Figure 4). The stance phase can be further divided into single limb and two double limb support phases (134). The stance and swing phases can be further divided into seven functional phases (Figure 4). The stance phase begins with heel contact with the ground (initial contact) and ends with toe-off of the same foot (134,136). Mid- and terminal stances occur in the single 26 limb support phase. In the pre-swing, the limb prepares for the swing phase and forward movement is the final phase of stance (116,137). The swing phase begins with toe-off and terminates with heel-strike of the same limb (Figure 4). During the initial swing, the leg is elevated, the limb is moved by hip flexion, increased knee flexion and angle joint partly dorsiflexion. The middle swing period begins when the swinging limb is opposite to the stance limb, which is in middle stance. The swing phase ends with the terminal swing, in which limb movement is completed as the shank moves ahead of the thigh (116). 27 Figure 4. a) The normal gait cycle phases. This cycle is divided into stance (60% of the gait cycle duration) and swing (40% of the gait cycle duration) phases. Load. resp. = loading response, Term. swing = terminal swing, Dbl. supp. = double support. Stance and swing 28 phases divided into seven functional events: IC initial contact, OT opposite toe off, HR heel rise, OI opposite initial contact, TO toe off, FA feet adjacent, TV tibia vertical. Below the gait phases is illustration of step length and width. b) Sagittal plane angles, sagittal and frontal plane normalized (by body weight) moments of ankle, knee and hip joints over a normal gait cycle. Flexion and dorsiflexion angles, extensor and plantar flexor moments (sagittal plane), and adductor moments (frontal plane) are positive. A more detailed description is provided in the text. The exact neurological control system coordinates the pattern of motor activity during walking. These organized neural networks are called central pattern generators and they are responsible for creating the motor pattern and are located in different parts of the central nervous system. This network produces the rhythm and shapes the pattern of the motor bursts of motoneurons (138,139). The central pattern generators can produce spontaneous locomotor bursts in the complete absence of peripheral feedback. Normally the central pattern generators produce the rhythmic locomotion by receiving information from both the central and peripheral nervous systems (138). 2.4.2 Biomechanics of stair walking Stair walking is a much more demanding task and requires more muscle strength than needed for level walking (140). The gait asymmetry increases in stair ambulation, especially in stair descent (141). Stair walking is similar to level walking in that it has a swing phase lasting approximately 36% of the full gait cycle and a stance phase lasting approximately 64% of the cycle and these are further subdivided. It is also known that stair walking produces greater forces and moments (141-143). The stance phase is subdivided into weight acceptance, pull-up and forward continuance. The swing phase is subdivided into the foot clearance and placing the foot appropriately so that the weight can be accepted for the next stance phase (144). 29 2.4.3 Gait analysis Gait analysis is a useful clinical tool for determining gait disabilities and it can provide quantitative information to help in the provision of optimal treatment (145,146). Medical physicians, professionals and biomechanists have been able to quantitatively estimate appropriate rehabilitation strategies (147-149) or surgical techniques (150) after the patient has undergone measurement of joint kinematics and kinetics. Gait analysis has also established itself as an important tool in defining the biomechanical factors that may affect the progression of pathologic conditions, such as knee OA (151-153). The aim of the gait analysis is to identify the gait phases, determine the spatiotemporal (i.e. walking speed, stride length, stride frequency and contact times), kinematic (i.e. joint angles, angular velocities and accelerations) and kinetic (i.e. body accelerations, ground reaction forces, joint moments) parameters of human gait events and to quantitatively evaluate musculoskeletal functions (i.e. muscle activity and power). This can be achieved by using different types of sensors i.e. to evaluate acceleration with SMAs, the actions of muscles with EMG, plantar pressures with pressure measurement insoles, ground reaction forces (GRFs) with force plates, and joint angles with goniometres (116,154). All this information can be merged with data from modern photography based on video recording of gait with high speed video cameras (116,137) (Figure 5). 30 Figure 5. Measurements of normal gait laboratory including the camera system, force platforms, accelerometers, electromyography and pressure insoles. The camera system and force platforms are synchronized with the aid of photocells. A more detailed description is provided in the text. 31 GRF has been used to define the gait pattern (155,156), and the stability of gait and posture (155). A force platform provides information about the ground reaction force; this has equal intensity but is in the opposite direction to the forces experienced on the foot of the weight bearing limb. With the aid of force platforms, it is possible to determine the three-dimensional GRFs in the vertical, anterior-posterior (AP) and medial-lateral (ML) directions. The vertical GRF peak is approximately 110% of body weight. During walking, the first peak appears at the burst of mid-stance as a reaction to the weight-accepting events during the loading response. The second peak appears in the late terminal stance and reflects the downward acceleration. The AP GRF appears at initial contact and in the opposite direction of walking. The magnitude of AP GRF is about 25% of body weight. The ML GRF appears when the body weight shifts from one limb to the other directing medially in the mid-loading response and then laterally in the terminal stance. The magnitude of ML GRF is about 10% of body weight (116) (Figure 5). The measurement of the knee joint moments provides a more direct indication of the actual knee joint loads. The external moments are the moments generated about the joint centre from the ground reaction forces and the inertial forces. The external moments are equal and opposite to the net internal moment, which is mainly created by muscle forces, soft tissue forces and contact forces (157). The internal knee extension moment is induced at the initial contact of the stance phase. In the loading response, the internal knee flexion moment is induced. In the midstance, the flexion moment decreases and the extension moment increases, a process which lasts throughout the terminal stance. At the preswing, a flexion moment is created again (116). The external knee adduction moment is associated with the distribution of forces between the medial and lateral compartments of the knee joint (157). The external knee adduction moment affects the knee joint throughout the stance phase, inducing two peaks during the first half or the late stance (158). 32 2.4.3.1 Accelerometers The use of triaxial accelerometers makes it possible to measure walking stability and the output from an accelerometer has been reported to represent a stable indicator of overall body movements (159-161). Accelerometers such as SMAs are inexpensive devices, noninvasive and small and therefore testing can be conducted outside the laboratory environment. SMAs have been widely used in studies which have reported differences between normal and pathologic gait patterns (162-165). SMAs attached to the lower limb (166-169) or affixed onto the lumbar spine (170-173) have been used in many studies evaluating gait kinematics and kinetics. Previous usage also includes quantification of physical activity levels (174-176), establishing spatial-temporal gait variables (173,177,178), evaluation of hip joint loading patterns (179,180), and the estimation of balance and stability during locomotion (161,181,182). SMA measurements have to be repeatable if the collected gait data can be used as an aid in diagnostics, treatment and rehabilitation. Several authors have emphasized that SMAs represent a repeatable method for evaluating gait (24,159,181,183-186). Only two studies have estimated the repeatability of acceleration measurements from SMAs attached to the level of the knee joint during walking (24,186). Turcot et al. (186) reported that the reliability (intraclass correlation coefficient (ICC)) of SMAs were greater than or equal to 0.75 in knee OA patients during treadmill walking at self-selected and accelerated speeds. Liikavainio et al. (24) demonstrated that SMAs achieved good repeatability (CV < 15%) during walking at self-selected and constant gait speeds in young healthy subjects. However, the repeatability of acceleration measurements from SMAs attached to the level of the knee joint during stair walking in healthy subjects or in knee OA subjects has not been investigated. 2.4.3.2 Electromyographic measurements EMG measurements have been incorporated into studies of human locomotion and used widely over the past decades for the investigation of normal and pathological gait (145,183,187-191). EMG measurements can allow an assessment of muscle activity in 33 human gait and thus they play an important role in estimating the walking performance of individuals with problems in their lower extremities (192). The reliability of EMG during gait evaluation has generally been shown to be good (183,193-195), but the repeatability of surface EMG in stair walking in healthy subjects has not been studied and there have been published only one study on repeatability of surface EMG on a knee OA population (194). 2.5 GAIT CHANGES IN OBESE SUBJECTS 2.5.1 Spatiotemporal variables Several authors have concluded that obese subjects have a lower preferred walking speed than normal-weight subjects (3,196-201). Obese subjects have been found on average to walk about 0.3 m/s slower and have a 0.1/s lower walking speed relative to body height (5). Furthermore, the reduction in the gait speed seems to be correlated with the increasing BMI (198,200). However, there are also studies in which the authors could find no significant difference in gait speeds between obese and normal-weight subjects (201,202). The obese and overweight individuals may walk with a shorter stride length and at a higher frequency (3,196,203) and have a greater step width (3,196) than normal-weight individuals. In addition, in comparison with normal-weight individuals, obese people have been reported to display a longer stance phase duration (199,204-207), a shorter swing phase duration (3,202,206,207,207) and a greater period of double support phase (3,202,207). A few authors have also reported that obesity does not cause any statistically significant difference in stride length and frequency (206,207). These changes would partially result from the reduced gait speed in obese subjects. Browning et al. (206) observed that stride characteristics decreased and double support time increased when gait speed decreased. 34 2.5.2 Gait kinematics It has been noted that joint kinematics in obese individuals may change in gait, but it is not obvious whether the altered kinematics describe a unique gait characteristic in obese or merely an adaptation to a slower walking speed (208). The impact of obesity on joint kinematics has been only occasionally studied (208). A few authors have detected differences in the hip joint (3,199,207,209), the knee joint (199,201,203,206,209), and ankle joint (3,196,199,205,210) angles during walking at self-selected and standardized gait speeds. Unfortunately, the different study designs and differences in walking speeds make it difficult to draw convincing conclusions about whether obese subjects have different joint kinematics than their non-obese counterparts. 2.5.3 Gait kinetics The studies of gait kinetics in obese individuals have mainly focused on evaluating joint loading by calculating GRFs (206,211) and joint moments during gait (197-199,201,203,205207). Some other studies have focused on determining joint powers (198,207). Browning et al. (206) showed that absolute AP and ML GRFs were significantly greater in obese subjects in comparison to lean individuals and these values increased significantly at higher gait speeds in both study groups (206). However, Browning et al. (206) found no difference between obese and normal-weight subjects when GRFs were scaled to body weight and showed that the absolute differences between groups decreased when walking at a lower gait speed. In addition, de Castro et al. (211) detected higher absolute and normalized AP and vertical GRFs in obese subjects compared to normalweight subjects during self-selected overground-level walking. Messier et al. (212) observed that there was a positive correlation between BMI and peak GRFs in obese subjects with knee OA. There are substantial differences in the reports investigating parameters related to the ankle, knee and hip joint moments associated with walking in obese healthy 35 individuals. These differences might be partly explained by gait speed (e.g. standardized versus self-selected gait speed) or the method of normalizing (e.g. normalize to body mass, fat free weight and height) the absolute joint moment values. By walking at a lower gait speed and with shorter strides, obese individuals may be attempting to reduce moments and maintain a magnitude of normalized joint loading relative to non-obese subjects (3,5,199,206,207,212). However, most of the studies have reported no statistically significant differences in the relative ankle, knee and hip joint sagittal moments between obese and normal-weight individuals during walking at a self-selected gait speed (198,199,205,207). DeVita and Hortobágyi (207) found less absolute knee joint moment in the sagittal plane in obese individuals walking at their self-selected gait speed, but equal knee and hip joint moments when walking at the same speed as normal-weight individuals. However, the absolute ankle plantar flexion moment was statistically higher and the peak knee extensor moment scaled to body mass was more substantially decreased in obese subjects than in normal-weight individuals. They postulated that a reorganized neuromuscular function in obese subjects could evoke a gait pattern with less total load on the knee joint (207). Browning et al. (206) found mainly higher absolute peak hip extension moment in the obese compared to normal-weight individuals during walking at all standardized gait speeds ranging from 0.5 m/s to 1.75 m/s. The absolute peak ankle plantar flexion and knee extension moments did not differ statistically between the groups except for the knee extension moment during walking at 1.75 m/s gait speed. The relative peak knee and hip extension moments on each gait speed did not differ significantly between groups, but the relative peak ankle plantar flexion moment did seem to be significantly lower at every gait speed (206). Further, Freedman Silvernail et al. (197) found no statistical differences in scaled (fat free weight and height) peak external knee flexion moment between obese and normal-weight individuals during walking at a standardized gait speed. 36 Several authors have evaluated the joint moments in the frontal plane in obese individuals. Browning et al. (206) showed that the absolute peak external knee adduction moment was significantly higher in obese than normal-weight subjects, but this difference between groups disappeared after normalizing the adduction moment to the body mass (197-199,201). On the contrary, Russell et al. (203) could observe no statistically significant differences in absolute peak external knee adduction moment between obese and nonobese subjects. Furthermore no statistically significant difference was detected in the scaled hip adduction moment in a comparison between obese and non-obese subjects (198,199). 2.6 EFFECTS OF WEIGHT LOSS ON GAIT CHARACTERISTICS 2.6.1 Conservative weight loss interventions Larsson et al. (213) found that after 12 weeks’ diet, gait speed increased significantly and improvements were still seen after 64 weeks compared to baseline in obese women (213). Similarly, Plewa et al. (214) reported significantly 4.5% faster walking speed, 2.4% longer stride length, 1.4% higher swing time, 0.8% lower stance time, 3.0% lower double support time, 1.8% shorter cycle time and 2.3% higher cadence during walking on a 10-m long walkway after three months’ diet plus exercise weight loss treatment and an averaged weight reduction of 7.4% compared to baseline measurements. In their randomized control study, Villareal et al. showed that a weight loss of in the range 1 to 10% from baseline led to a 14% to 23% increase in the fast gait speed from baseline in their exercise and diet-exercise groups (41). Song et al. (215) conducted a randomized controlled trial study to investigate the effects of weight loss on temporo-spatial gait parameters in obese adults. They observed a significantly greater reduction only in the support base of gait compared to the control group after a three month weight loss intervention (diet plus exercise) and weight reduction of 5.9 kg (215). 37 A randomized clinical trial of overweight and obese older adults with knee OA studied the effects of four distinct 18-month interventions i.e. exercise only, diet only, diet plus exercise and healthy lifestyle (control) on gait during walking at a self-selected gait speed (19,216). The study groups of the diet alone and the diet plus interventions experienced significantly more weight loss than the group recommended to adhere to a healthy lifestyle (216). The weight loss was significantly associated with a reduction in compressive knee joint loads. They reported the 1:4 ratio of weight loss to load reduction, which meant that for every 0.45kg of weight loss, there was a 1.8kg reduction in knee joint load per step (19). Messier et al. (217) in their secondary data analysis evaluated the effects on gait characteristics of the weight loss in their knee OA subjects subdivided into whether they lost over or less than 5% weight as well as in those who did not lose/gain weight. The gait speed increased by 6.8% and 7.4% in the high and low weight loss groups, but not in the control group. The maximum knee compressive forces were lower with greater weight loss, but the knee abduction and extension moments did not differ between high and low weight loss groups (217). A 16-week dietary intervention which achieved a 13.5% weight loss from the baseline body weight, significantly increased self-selected gait speed and this was accompanied by a 7% reduction in peak knee compression force, a 13% lower axial impulse, and a 12% reduction in the internal knee abduction moment in obese knee OA patients (20). They reported that for every 1 kg of weight loss, there was a 2.2 kg reduction in the peak knee joint load at any given gait speed (20). Thus, it seems that obesity increases the knee joint loads and that weight loss exerts positive effects on the knee joint loads in obese knee OA subjects. However, there is evidence that an increased knee joint loading for one year was not related to accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads (218). 38 2.6.2 Bariatric surgery A few studies have investigated on gait characteristics of the effects of massive weight loss induced by bariatric surgery. Hortobagyi et al. (21) studied the effects of the surgery induced weight loss on kinematics and kinetics of the gaits of healthy obese subjects for up to 12.8 months after the bariatric surgery. The obese subjects experienced an average 33.6% (42.2kg) weight loss. Weight loss subjects increased their swing time significantly by 7.1% and 4.7% and made 7.9% and 3.2% longer strides during walking at self-selected and standard gait speeds. The self-selected gait speed increased by 11.6% and the cadence decreased by 1.2% during walking at standard gait speed. The obese gait was stated as being more dynamic because of the increased hip joint range of motion during the swing, increased knee flexion during early stance and ankle function shifted to a more plantarflexed foot. In addition, after the weight loss, the normalized knee joint moments increased in the sagittal plane and absolute ankle joint moments and knee joint moments in frontal plane decreased (21). Vincent et al. reported that weight loss subjects had a 7.9±2.5 kg/m2 lower BMI, a 15% faster gait speed, a 4.8 cm longer step length, a 2.6% longer single support time and a 2.5 cm smaller step width three months after bariatric surgery, but there were no changes observed in either the stride length or the cadence. Froehle et al. (219) investigated the effects of weight loss on gait characteristics in women 5 years after Roux-en-Y gastric bypass surgery. They reported that the degree of excessive body weight loss was correlated with less time spent in initial double support and more time in single support. 39 3 Aims of the Study The objectives of the present series of studies were: 1) To review the current literature involving the effects of obesity and weight loss on gait characteristics and to investigate how BMI affects the impulsive loading on the level of the knee joint (I). 2) To investigate the changes in physical function and HRQOL and the properties of the QFm in severely obese subjects after bariatric surgery and the subsequent weight loss (II). 3) To determine the repeatability of SMAs for evaluating accelerations at the level of the knee joint in level and stair walking at pre-determined gait speeds in combination with simultaneous EMG measurements of the lower extremities in healthy and knee OA subjects (III). 4) To study the knee joint impulsive loading in level and stair walking in severely obese subjects after bariatric surgery and the subsequent weight loss (IV). 5) To examine the postural stability and function of vastus medialis (VM) and biceps femoris (BF) muscles with surface EMG in knees of OA subjects and to compare the results with those of age- and sex-matched healthy controls (V). 40 4 Experimental Procedures 4.1 SUBJECTS AND SELECTION A total of 143 volunteers (18 women and 125 men) participated in three different experiments (1-3). The clinical characteristics and features of subjects are presented in Tables 5, 6 and 7. The studies were approved by the Ethics Committee of the Kuopio University Hospital. The subjects in Experiment 1 (Papers I, V) were recruited via a local newspaper advertisement from the city of Kuopio, Finland and its neighbouring area. Fifty four male subjects were selected for the study based on clinical criteria for uni- or bilateral knee OA as indicated in the clinical criteria of the American College of Rheumatology (131). The fifty three age-matched men as controls were randomly selected from the population register of the city of Kuopio. None of the controls had hip or knee OA according to clinical criteria of American College of Rheumatology (131). The knee OA subjects in Experiment 1 were further divided into three BMI categories, normal weight (BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (BMI ≥ 30 kg/m2) (Paper I). The exclusion criteria of the subjects in Experiment 1 are shown in Table 4. The healthy subjects without knee OA (5 females and 4 males) in Experiment 2 (Paper III) were recruited from the medical students of the University of the Eastern Finland. None of the controls had any knee or hip pain or functional impairments in their lower extremities. The nine knee OA male patients in Experiment 2 were sampled from knee OA population from Experiment 1. The exclusion criteria of the subjects in the Experiment 2 are shown in Table 4. 41 Table 4. Exclusion criteria for Experiments 1, 2 and 3. Experiment 1 and 2 A history of previous hip or knee fracture Surgery of the lower extremities (knee arthroscopy was allowed) Surgery to the vertebral column A history of other trauma to the hip joint or in the pelvic region Symptomatic hip OA A knee or hip joint infection Congenital or developmental disease of the lower limbs Paralysis of the lower extremities Any disease or medication that might have worsened physical function and interfered with the evaluation of knee pain, such as: cancer severe mental disorder rheumatoid arthritis or spondylarthritis symptomatic cerebrovascular disease endocrine disease epilepsy Parkinson’s disease polyneuropathia, neuromuscular disorder debilitating cardiovascular disease in spite of medication atherosclerosis of the lower extremities painful back corticosteroid medication symptomatic spinal stenosis acute sciatic syndrome Experiment 3 A previous knee or hip arthroplasty Other current disabilities of the hip, knee or ankle joint (e.g., fractures, ligamentous instability) The subjects in Experiment 3 (Papers II, IV) were recruited from the Unit of Clinical Nutrition at Kuopio University Hospital, Kuopio, Finland. The inclusion criteria consisted of the subjects being evaluated for bariatric surgery and willingness to participate in the Experiment 3. The exclusion criteria are shown in Table 4. Fifteen female and three male participated in Experiment 3 in the baseline measurements and sixteen (13 women and 3 men) of the original subjects participated in the follow-up in study II. 42 4.2 EXPERIMENTAL DESIGN 4.2.1 Experiment 1 Experiment 1 investigated the postural stability and function of VM and BF muscles in knee OA subjects in comparison with those of age- and sex-matched healthy controls (Paper V) and how BMI affected the impulsive loading on the level of the knee joint (Paper I) using the Kuopio Knee OA Study subjects (25). Gait analysis (Paper I) was performed in the Department of Applied Physics, University of Eastern Finland. The subjects walked barefoot along the 10-m long laboratory walkway at a standardized walking speed (1.2 m/s ± 5%). Impulsive joint knee loading was assessed with SMAs (Mega Electronics Ltd, Kuopio, Finland) (see details in paragraph 4.3.4 Acceleration measurements). The postural balance measurements (Paper V) were performed in the Department of Applied Physics, University of Eastern Finland. The subjects stood barefoot on the force platform (AMTI model OR6-7MA, Watertown, MA USA) in three different conditions; bipedal stance with eyes open and closed and monopedal stance with eyes open (both legs separately). The trial order was randomized. Testing under each condition was performed three times, each lasting 30 seconds. The testing session ended when there was loss of balance. The best performance of the three trials over the duration of 5, 10 and 30 seconds was subsequently analysed (see details in paragraph 4.3.7 Postural stability measurements). The subjective severity of knee pain was rated on VAS (range 0-10 cm; end points: no pain-unbearable pain). The pain history was inquired separately for the right and left knee joints after completing the balance measurements. In addition, the maximal voluntary isometric knee extension and flexion torques were determined in the Department of Physical and Rehabilitation Medicine, Kuopio University Hospital. 43 4.2.2 Experiment 2 The repeatability of SMAs in level and stair walking at a pre-determined gait speeds in combination with simultaneous EMG measurements of lower extremities in healthy and knee OA subjects were evaluated in Experiment 2 (Paper III) The gait analysis was performed in the Department of Physical and Rehabilitation Medicine, Kuopio University Hospital on the walkway and the stairs. All subjects walked both along the 15 m long walkway and along the main axis of the ordinary stairway. Gait speed was measured using a pair of photocells at knee joint level. In the walkway, the photo-cells were positioned 6 m apart from each other and permitted the measurement of 3 gait cycles with 6 consecutive steps for each subject. In stair walking, the five consecutive gait cycles were taken in the analysis from each trial. During the measurements, the subjects walked with plain shoes without any dampers in the soles at their self-selected gait speed and a pre-determined constant gait speed of 1.2 m/s along the walkway and at a pre-determined gait speed of 0.5 m/s both up and down the stairway. A trial was accepted if the gait speed was within ±5% of the target speed. The trial order was randomized. The same test protocol was repeated after 2 weeks in order to assess the repeatability of the SMA and EMG measurements (see details in paragraphs 4.3.4 Acceleration measurements and 4.3.6 Measurements of electromyography). 4.2.3 Experiment 3 Experiment 3 evaluated the effects of bariatric surgery and a subsequent weight loss on physical function, HRQOL, properties of the QFm and knee joint impulsive loading in level and stair walking in severely obese subjects (Papers II, IV). Measurements were performed before and 8.8 months after the Roux-en-Y gastric bypass surgical procedure which was conducted in the Kuopio Univeristy Hospital. Participants filled in questionnaires concerning their self-reported disease-specific joint symptoms (WOMAC), HRQOL, comorbidities, work history, use of pain relief 44 medication and leisure-time physical activity. The radiological measurements (evaluation of plain radiographs and ultrasound measurements of QFm), anthropometric measurements, knee and hip joint ROM and blood biochemical measurements were made (Paper II). Detailed descriptions of the questionnaires and radiological measurements are shown in paragraphs 4.3.1 and 4.3.2. Subjects also performed physical function tests (Paper II). Before undertaking the actual physical function tests, the subjects were familiarized with the experimental protocol and purpose. The physical functioning was performed in a randomized order except for the 6-min walk which was always conducted at the end of the session. Detailed descriptions of the tests are shown in paragraph 4.3.8 Physical function measurements. Gait analysis in Experiment 3 (Paper IV) was performed in the Department of Applied Physics, University of Eastern Finland. The characteristics of the gait were measured in both the laboratory and on the stairway. There were two force platforms mounted in the middle of the 10-meter long walkway to allow the measurements of the GRFs. Gait speed and start trigger generation were obtained by using a pair of photo-cells placed at shoulder level and custom Labview 2010 (National Instruments, TX, USA) software. The photo-cell zone was monitored 2.20 meters in the middle of the walkway. Stair walking trials were performed in an ordinary stairway (Figure 6) (25). 45 Figure 6. Illustration of gait measurement setup. Gait measurements were completed both in the 10 m walkway of the laboratory and on the stairway. Acceleration was assessed with triaxial SMAs attached over the medial surface of the proximal tibia. Two force platforms mounted in the walkway were used to measure GRF. Gait speed was measured using a pair of photo-cells. During the measurements, the subjects walked barefoot at two pre-determined gait speeds of 1.2 m/s and 1.5 m/s along the walkway in the laboratory and on stairway at a pre-determined gait speed of 0.5 m/s, performing stair ascent and descent separately. The trial order was randomized in every phase. A trial was accepted if the gait speed was within ±5% of the target speed. Six successful trials were obtained at each speed in the laboratory, while four successful trials were required on the stairs in both directions. 46 4.3 DATA RECORDING AND ANALYSIS 4.3.1 Questionnaires In Experiment 3, the subjects filled in a questionnaire to gather information on the physical activity of occupations [scale from 0 (no work) to 6 (in physical terms, the most demanding occupation)] (220), the use (no use, 1-2 times per week or 3-4 times per week or over 5 times per week) of prescribed pain relief medication (e.g. paracetamol, nonsteroidal anti-inflammatory drugs (NSAID) or weak opioids) during the previous month and the intensity of leisure-time physical activity (scale from 1 to 3; 1= rare activity, 2= occasional activity, 3= frequent activity). The WOMAC OA index (Visual Analogue (WOMAC VA 3.0) scaled format), which has been validated for the assessment of outcomes involving knee OA (221) was used to evaluate the self-reported disease-specific joint symptoms (pain, stiffness and physical function) in knee OA patients and the RAND-36 questionnaire was used to evaluate the self-reported HRQOL. 4.3.2 Radiological measurements Evaluation of plain radiographs In Experiments 1, 2 and 3, the AP weight bearing and lateral radiographs of both knees as well as the weight bearing radiographs of the lower limbs and pelvis were taken. The radiographs were evaluated using the K-L grading (129), in which grade t1 or grade t2 were regarded as OA. The knee varus or valgus alignment (degrees) was assessed in Experiment 1 using the method described by Moreland et al. (222). Ultrasound measurements Ultrasound measurements with a 5-cm wide probe of 5 MHz frequency (SSD 1000; Aloka Co, 6-22-1, Mure, Mitaka-shi, Tokyo, 181-8622, Japan) were taken to determine the 47 properties of the QFm from the midpoint of the rectus femoris (RF), the vastus lateralis (VL) and VM compartments (9) in Experiment 3. The midway between the lateral joint space and the trochanter major was chosen as the measurement point. The thickness (cm) of the subcutaneous fatty tissue and the thickness of the muscle tissue, including the RF, VL and VM muscles, were measured by means of a longitudinal real-time scan while the subjects were lying in the supine position. Furthermore, Image J version 1.46r for Windows software (available as freeware from http://rsbweb.nih.gov/ij/) was used to analyze the ultrasound images. The muscle CSA (cm²) beneath the probe and mean echogenicity of the three muscle compartments were calculated to estimate the muscle mass and tissue composition (223,224). The ratio of muscle CSA/ total body weight was also determined. The echogenicity is a measure of muscle composition which utilizes the 256 grey shades of the device. The increased echo intensity (echogenicity i.e. higher mean grey shade value) of the muscle was assumed to reflect increased tissue composition heterogeneity i.e. increased fat and connective tissue proportion (223,224). The ultrasound method and its good repeatability with in elderly women, athletes, untrained men and obese adolescents have been described in more detail elsewhere (223-225). The quantitative ultrasound measurements have been reported to correlate with the computed tomography measurements of muscle cross sectional area and also with muscle composition measurements in elderly trained and untrained women (226). The ultrasound can be considered as the diagnostic method before and after bariatric surgery (227). 4.3.3 Anthropometric measurements, knee and hip joint range of motion, knee muscle strength and blood biochemical measurements In all Experiments (1-3), the BMI (kg/m²) was calculated. The thigh circumference (cm) was measured midway between the lateral joint space and the trochanter major in Experiment 3. 48 The ROM of the knee and hip joints was measured with a standard goniometer method (9,228) (Experiment 3). The maximal isometric voluntary knee flexion and extension contractions (Nm/kg) were performed by using a Lido dynamometer (Lido® Active Isokinetic Rehabilitation System, Loredan Biomedical, West Sacramento, CA, USA)(9) (Experiment 1). The strength measurements were made in the sitting position, the thigh fixed on the seat and the ankle attached to the moment arm above the malleolus. The knee and hip angles were settled at 70°. The plasma glucose level, total cholesterol, HDL cholesterol and total triglycerides were analysed using the automated analyzer systems at the Central Laboratory of Kuopio University Hospital (ISLAB) (Experiment 3). 4.3.4 Acceleration measurements In Experiments 1-3 SMAs (Meac-x ®, Mega Electronics Ltd; Kuopio, Finland) were attached to the medial surface of the proximal tibia at 20% of the distance between the medial malleolus and the medial knee joint space (tibial plateau) and held in place by an adhesive bandage (Fixomull stretch) and straps (24) (Papers I, III, IV) (Figure 6). The positive z-axes az of the sensor were aligned to be parallel to the straight limb and ax and ay axes were parallel to the horizontal directions. The range of the accelerometers is ± 10 g, the resolution is 0.0015 g and the sampling rate is 1000 Hz. A 16-channel portable device with WLAN connection (Biomonitor ME6000 T16 data-acquisition unit, Mega Electronics Ltd, Kuopio, Finland), tied to the subject’s waist with a cloth belt, was used to collect SMA data (Figure 6). All data were further analysed with MATLAB R2010a (Mathworks Inc.; MA, USA) based software developed in the Department of Applied Physics, University of Eastern Finland (25). Initial peak acceleration (IPA) (Papers I, III, IV), the maximal acceleration transient rate (ATRmax) (Paper III) (24) and the root mean square acceleration (RMS) (186) (Paper III) were determined for axial az, resultant ar, and horizontal resultant a xy a x2 a y2 (ML and 49 AP directions) directions (24). The peak-to-peak acceleration (PP) in both az and axy directions was determined in Paper IV and Paper I (only axial direction). 4.3.5 Ground reaction force measurements In Experiment 3 (Paper IV), the three-dimensional GRFs were measured with two force platforms (AMTI model OR6-7MA, Watertown, MA, USA) embedded in the walkway (Figure 6). It was possible to measure two consecutive steps with the force platforms and three acceleration steps were allowed up to the walkway before reaching the platforms. The GRF data during stance phase were collected and stored with AMTI software at 1000Hz. All parameter values were determined utilizing software developed in MATLAB R2010a environment (Mathworks Inc.; MA, USA). The analyzed GRF parameters FV, FAP, and FML referred to the vertical, AP, ML GRF components, respectively (24,25). The analyzed GRF parameters were: peak braking (FAP1) and propulsion (FAP2) force, vertical peak forces during braking (FV1) and propulsion (FV2) phases, peak ML force (FML1), and maximum loading rate (LRmax) which was obtained from the maximum slope of the FV at the heel strike transient. All GRF parameters were generated in absolute (Newtons, N) values, and GRF changes between baseline and follow-up were generated in both absolute and normalized values. The normalized changes were defined first as the mean of individual percentual changes (MIPC), and subsequently, as the MIPC difference from the mean weight loss. 4.3.6 Measurements of electromyography The surface muscle activity was measured from VM, BF (Paper III, V), tibialis anterior (TA) and gastrocnemius medialis (GM) muscles (Paper III). The EMG was recorded according to SENIAM recommendations with bipolar surface Ag-Cl electrodes (M-00-S, Medicotest A/S, Olstykke, Denmark) (229). 50 In Experiment 1 (Paper V), the cut-off frequencies of 7 Hz and 500 Hz were used to achieve bandpass filtering of EMG signals, which were then amplified by the ME6000 system (details in paragraph 4.3.4 Acceleration measurements). The raw EMG data was processed and analysed with Matlab version 7.3 (Mathworks Inc.; MA, USA). All digitized EMG signals were full wave rectified and averaged. The sampling frequency was 2000 Hz. The maximum EMG signal determined during walking in the corridor at 1.5 m/s was used in the normalization of EMG activity. Root mean square (RMS (muscle activity (%)) for EMG amplitude, mean EMG frequency (fEMG,mean) and median EMG frequency (fEMG,med) of motor unit activity were evaluated from the normalized EMG data. In Experiment 2 (Paper III), the EMG data was collected with the sampling rate of 1000Hz and signals were band-pass filtered with cut-off frequencies of 7 Hz and 500 Hz and amplified by the Biomonitor ME6000 system (details in paragraph 4.3.4 Acceleration measurements). The raw EMG data was processed and analysed with MATLAB R2010a environment (Mathworks Inc.; MA, USA). Then, all digitized EMG signals were full wave rectified and averaged as the mean activity over a gait cycle. The activation estimate of the EMG signal obtained during walking up stairs at 0.5 m/s was used for the normalization of the EMG activity. The mean EMG activation (EMGact; % of maximal motor unit activity) was evaluated from the normalized EMG data (229). 4.3.7 Postural stability measurements In Experiment 1 (Paper V), the postural sway was determined as the track of the center of pressure (COP), which approximates the location of the resultant force below the feet and can be calculated from the force plate data (230,231). All data analyses were performed using software developed in Matlab version 7.3 (Mathworks Inc.; MA, USA). The following posturographic parameters from each trial COP track with durations of 5, 10 and 30 s were evaluated in the time domain: 51 x The velocity along AP (VAAP (mm/s)) and ML (VAML (mm/s)) axes, and mean sway velocity (MSV (mm/s)). x Elliptical area (EA (mm2)), standard deviation of COP (SDCOP) in AP and in ML directions, SDCOPAP (mm) and SDCOPML (mm), respectively. x Average radial displacement (ARD (mm)) from the centroid of COP xc , yc over the entire trial (232). x Mean frequency (MF) The power spectral density (PSD) estimates were used to evaluate frequency domain balance parameters. The following parameters were evaluated from PSD estimates: x Mean balance frequency fbalance,mean (Hz) and median balance frequency fbalance,med (Hz) in both AP and ML directions. x PSDs were divided into four frequency bands: Very low frequencies (0–0.15 Hz), low frequencies (0.15–0.5 Hz), high frequencies (0.5–4 Hz) and very high frequencies (> 4 Hz). 4.3.8 Physical function measurements The objective physical function was investigated with a battery of physical function tests in Experiment 3 (Paper II): Sock test The subject was asked to simulate putting on a sock in a standardized manner for both feet (233). Scoring was from 0 to 3, where a score of 0 meant that the test did not cause any difficulty and a score of 3 was awarded when there was an inability to reach as far as the malleoli. After testing both legs, the subjects were scored according to the most restricted performance. The reliability of the sock test has been determined to be acceptable (233). 52 Repeated sit-to-stand test The subject was asked to fold the arms across his or her chest and to stand up from a sitting position and to sit down five times as quickly as possible. The result was calculated from the two-run time average (234,235). The reliability of this test has been shown to range from good to high (236). Stair ascending and descending test The subjects walked up and down twelve stairs as quickly as possible. Ascent and descent were performed separately three times and the mean velocity (m/s) of 3 trials was considered as the result of the test. The reliability of this test of stair ascent and descent has been demonstrated to be excellent (228). Timed Up and Go Test (TUG) The subjects were asked to stand up from a standard-height chair with arm rests, walk 3 meters, turn, walk back and sit down again as quickly as possible. The mean time of three trials was determined with the result counted in seconds (237). TUG measurements have displayed high test-retest reliability (238) 6-minute walk test The subjects walked a-20-m distance back and forth for 6 minutes. The participants were asked to “walk as quickly and safely as you can for 6 minutes”. The result was the total distance traveled (meters) during 6 minutes (239). Steffen et al. (238) have reported high reliability with the 6-minute walk test. 4.3.9 Statistical analysis Mean values and the standard deviations (SD) were calculated for the measured parameters. The normality of the distribution was determined by the KolmogorovSmirnov test and the quality of variances by the Levene test and Lilliefors tests. The results 53 were regarded as significant if p < 0.05. Student’s t-test was performed for the parameters, which were normally distributed. The corresponding nonparametric tests (Mann-Whitney, Kruskal-Wallis and Wilcoxon) were used for ordinal scale parameters and for variables when the presence of a normal distribution could not be assured. In Experiment 1 (Papers I, V), the one-way analysis of variance (ANOVA) (Papers I and V) and the multivariate analysis of variance (MANOVA) (Paper V) were performed to determine the statistical differences in the continuous parameters between knee OA and control groups. Knee OA patients who had ≥ 1 difference in K-L grading between limbs (n=33) were selected for side-to-side comparison using mixed model analysis with age, height, weight and knee pain as covariates in the balance measurements (Paper V). The Pearson correlation coefficient was used to estimate the linear correlations between the normally distributed continuous variables (Paper V). The two-way random ICC (intra-class correlation coefficient) model (186,240) ICC2,k and the coefficient of variation (CV) were calculated to evaluate the reliability of acceleration and EMG measurements in Experiment 2 (Paper III). The ICC values greater than or equal to 0.75 were accepted as indicating sufficient repeatability. The repeatability was considered to be good if the CV was less than 15% (24,159,159). All statistical analyses were performed with SPSS statistics for Windows (SPSS Inc., IL, USA) and using MATLAB R2010a with Statistics Toolbox (Mathworks Inc.; MA, USA). 54 5 Results 5.1 CHARACTERISTICS OF SUBJECTS In Experiment 1 (Papers I and V), the knee OA patients were 10.2 kg (p < 0.001) heavier, 2.3 cm (p < 0.05) taller and had 2.6 kg/m² (p = 0.001) higher BMI values than the control subjects. The knee flexion and extension torques and knee varus or valgus malalignment were found to be statistically significantly 12.8% and 19.6% lower and 49% higher in knee OA group than the corresponding values in the control group, respectively. The age, weight, height, BMI and knee pain (VAS) did not differ statistically between the knee OA subgroups, neither did the knee extension nor flexion torques. The knee varus or valgus alignment and the knee extension and flexion ROM differed significantly between the subgroups. The clinical characteristics and features of subjects are presented in Tables 5, 6 and 7. In Experiment 3 (Papers II and IV), the obese subjects lost about 21.5% (27kg) of body weight between baseline and follow-up measurements when assessed 8.8 months after bariatric surgery. The BMI decreased by 21.6% from the baseline measurements. The knee flexion and hip external, but not knee extension ROM values in both legs were statistically improved after bariatric surgery. Thigh circumference was significantly smaller after bariatric surgery. Total plasma triglyceride and glucose levels decreased and HDL cholesterol level increased statistically weight loss. The use of pain medication did not change after bariatric surgery, except that there was less utilization of NSAIDs. The leisure-time physical activity increased 13.8 % after weight loss. The clinical characteristics and features of the subjects and the mean of individual measured parameters are presented in Tables 5, 6 and 7. There were no significant differences in the clinical features between knee OA subjects and non-OA subjects (data not shown). The knee extension ROM values were significantly (p < 0.05) lower in the knee OA group than in the non-OA 55 group in both baseline and follow-up measurements (data not shown). There were no significant differences between the OA group and the non-OA group in terms of work load history, leisure-time physical activity and number of comorbidities (data not shown). Table 5. Clinical characteristics of the subjects in Experiment 1, 2 and 3 (mean ± SD). Experiment Number Age (years) Weight (kg) Height (cm) BMI (kg/m²) Control group (n=53) 59.2±4.7 81.7±10.6 173.5±5.7 27.1±3.1 Knee OA group (n=54) 59.0±5.3 91.9±15.6 175.8±5.9 29.7±4.7 K-L 1 (n=12) 57.7±5.8 92.5±20.5 177.1±6.3 29.5±6.0 K-L 2 (n=15) 58.7±5.8 91.6±18.0 176.7±5.9 29.3±5.1 K-L 3 (n=19) 59.1±5.1 90.7±11.2 175.1±5.0 29.6±3.7 K-L 4 (n=8) 61.2±4.1 94.5±13.9 174.0±7.4 31.2±4.3 Healthy group (n=9) 22.7±1.4 65.7±11.0 172.4±8.5 22.0±2.0 Knee OA group (n=9) 62.7±5.1 82.4±9.9 175.0±5.8 27.0±4.2 45.1±9.5 127.0±19.7 169.8±8.5 44.0±5.3 1 (n=107) Original paper I, V 2 (n=18) III 3 (n=16) Baseline (n=16) Follow-up (n=14-15) 46.8±10.0 99.7±17.5 Baseline (n=15) 45.7±10.0 125.6±19.5 Follow-up (n=15) 46.8±10.0 98.2±17.1 II 34.5±4.8 169.9±8.2 43.3±4.8 IV 33.9±4.3 K-L = Kellgren- Lawrence knee OA grading scale, in which 0 refers to no knee OA and 4 refers to severe knee OA; BMI= body mass index. (54) Muscle strength (flexion) 2.13±0.77 1.09±0.43 -4.0±4.0 131.0±13.0 b <0.001 0.024 <0.001 <0.001 <0.001 pb 23.8±23.0 2.44±0.83 1.21±0.54 -3.0±4.0 137.0±12.0 4.3±2.1 K-L 1(12) Knee OA subgroups 5.1±2.8 K-L 3(19) 10.1±3.5 K-L 4(8) c ANOVA or Kruskal-Wallis; NS, nonsignificant. 0.003 pc 38.3±33.3 2.05±0.86 1.06±0.46 -3.0±2.0 26.3±21.0 2.23±0.57 1.15±0.30 4.0±4.0 43.3±29.7 1.55±0.68 0.82±0.42 -7.0±4.0 NS NS NS 0.047 131.0±5.0 132.0±11.0 120.0±19.0 0.014 4.6±2.4 K-L 2(15) Knee pain after balance measurements; (°), degrees; Student t-test for 2 independent samples or Mann-Whitney non-parametric test; a Knee pain a, VAS (mm) (Nm/kg) Muscle strength (extension) 2.65±0.55 -1.0±1.0 1.25±0.28 Knee extension (°) (Nm/kg) 145.0±6.0 5.5±3.2 (53) 2.8±1.7 Knee OA group Control group Knee flexion (°) Alignment (°) Variable Table 6. Clinical features of subjects in Experiment 1 (mean ± SD). 56 57 Table 7. Clinical features of subjects in Experiment 3 before (baseline) and after (follow-up) bariatric surgery (mean ± SD) (n=16, in laboratory test n=14-15). Baseline Follow-up Pd right leg 124.7±9.2 136.3±10.1 <0.001 left leg 126.6±8.9 135.9±10.0 <0.001 right leg -0.83±7.1 -0.94±7.6 NS lef leg -0.83±6.7 -0.31±7.6 NS right leg 36.9±9.3 40.0±9.0 NS left leg 35.9±7.6 39.4±5.1 <0.05 right leg 38.1±5.4 41.3±6.2 <0.05 left leg 38.1±5.1 45.3±6.9 <0.05 Thigh circumference (cm) 71.4±7.3 61.7±7.4 <0.001 paracetamol 31.3% 50 % NS NSAIDsa 43.8% 6.3% <0.05 Weak opioids 37.5% 31.3% NS Number of comorbidities (0-4) 2.0±1.15 Leisure-time physical activity (1-3)b 1.81±0.66 2.06±0.57 <0.05 Work load history (0-6)c Plasma total cholesterol (mmol/l 2.3±1.4 4.7±1.4 2.6±1.8 4.4±0.9 NS NS HDL cholesterol (mmol/l) 1.04±0.24 1.39±0.31 <0.001 Plasma total triglycerides (mmol/l) 1.78±1.4 1.12±0.48 <0.05 Plasma glucose (mmol/l) 6.5±1.8 5.7±1.0 <0.05 Variable Knee flexion (°) Knee extension (°) Internal hip rotation (°) External hip rotation (°) Pain medication (yes(%)) a non-steroidal anti-inflammatory drugs; b the scale from 1 to 3; 1= rare activity, 2= occasional activity, 3= frequent activity; c the scale from 0 (no work) to 6 (in physical terms the most demanding occupation); d Wilcoxon non-parametric test; NS, nonsignificant. 58 5.2 REPEATABILITY OF MEASUREMENTS WITH SKIN MOUNTED ACCELEROMETER AND ELECTROMYORGAPHY 5.2.1 Repeatability of acceleration measurements Healthy subjects RMS in the az direction exhibited good test–retest repeatability according to both the CV (range, 4.9% to 13.8%) and ICC (range, 0.95 to 0.96) during level walking and walking up stairs. The ranges of ICC and CV of the RMS acceleration in a r and axy were 0.62-0.87 and 5.7%-17%, respectively, depending on the type of walking. The ICC and CV of IPA in the az showed acceptable repeatability, ICC ranging from 0.94 to 0.98 and CV from 7.7% to 14.2%, respectively, during level walking and walking up stairs. Only the ICC of IPA in the resultant direction during stair walking was excellent. The ICC of IPA in a xy during walking down stairs was also excellent. The ICC and CV of ATR max in az during level walking and walking up stairs, and in ar during walking up stairs demonstrated good repeatability with ICC ranging from 0.85 to 0.99 and CV from 10.8% to 13.2%. The ICC and CV of ATRmax in ar during walking up stairs were found to be good. The ATRmax in az and ar in walking down stairs exhibited excellent repeatability according to ICC (range 0.82 to 0.85) (Paper III). Knee OA subjects RMS parameters in az and ar as well as axy showed good test-retest repeatability according to both the CV (range 8.4% to 10.9%) and ICC (range 0.75 to 0.84) during level walking. In addition, the RMS in axy during stair walking exhibited good repeatability according to both ICC (range 0.74 to 0.79) and CV (range 8.3% to 10.1%), respectively. The ICC of RMS in az and ar in walking up stairs and in ar in walking down stairs was found to be excellent (range 0.78 to 0.88). IPA in az and ar achieved excellent test–retest repeatability (ICC range 0.89 to 0.93) during stair walking. IPA in a xy exhibited good repeatability according to both ICC (0.76) and CV (14.1%) during walking down stairs (Paper III). 59 5.2.2 Repeatability of electromyography measurements Healthy subject The repeatability of EMGact in VM and BF was demonstrated to be good according to both the CV (range 12.1% to 14.2%) and ICC (range 0.77 to 0.84) in level walking. In TA muscle, the repeatability was excellent according to ICC only for level walking. EMGact in BF, TA and GM during walking up stairs exhibited excellent repeatability according to both the CV (range 8.8% to 14.1%) and ICC (range 0.91 to 0.97). The CV of EMGact in VM was demonstrated to be good (8.3%) during walking up stairs. The repeatability of EMGact in TA was excellent according only to the ICC (0.91) during walking down stairs (Paper III). Knee OA subjects The ICC and CV of EMGact in GM were 0.94 and 10.2%, respectively, during level walking. The EMGact in TA achieved good repeatability according to both the CV (13.4%) and ICC (0.77) in walking up stairs. Only the ICC of EMGact in GM was good during walking up stairs. The CV of EMGact in VM was good during walking up and down stairs. In general, EMGact during walking down stairs did not exhibit acceptable repeatability (Paper III). 60 5.3 EFFECTS OF OBESITY AND WEIGHT LOSS ON JOINT LOADING 5.3.1 Ground reaction forces Vertical and horizontal GRF parameters between the baseline and follow-up measurements are shown in Table 8 (Paper IV). All absolute GRF parameters were found to be statistically (p ≤ 0.020) lower after bariatric surgery. Only the normalized GRF parameter values FV2 at 1.2 m/s speed and FML1 at both 1.2 m/s and 1.5 m/s speeds increased by 3.4% (p = 0.039) and decreased by 11.0% and 9.7% (p = 0.009 and p = 0.036). The normalized GRF parameters were estimated as the MIPC value difference from the average weight loss (21.8%). None of the GRF parameters differed statistically significantly between knee OA and non-knee OA subjects. 5.3.2 Accelerations The knee SMA parameters before and after bariatric surgery are shown in Table 9 (Paper IV). IPA and PP in both az and axy directions decreased statistically (p ≤ 0.021) during level walking. Walking speed had an effect on the accelerations in the lower limbs, e.g. the higher gait speed, the higher the accelerations. None of the SMA parameters differed significantly between baseline and follow-up measurements during walking stairs down and up. None of the SMA parameters were found to be statistically significantly different between knee OA and non-knee OA subjects. The SMA parameters in different BMI categories are shown in Figure 7 (Paper I). IPA and PP accelerations in the axial direction increased in proportion to the BMI. The overall picture of the results demonstrated that overweight and obese individuals load their lower extremities more strongly than lean individuals when they make the initial contact with the ground. 61.3±24.2 88.1±22.8 1.5 88.7±24.8 1.5 1.2 80.3±25.2 239±43.7 1.2 208±29.5 1.5 235±60.7 1.2 201±43.4 1.5 1224±172 1.5 1.2 1251±169 1400±222 1.2 1305±188 1.5 Baseline 1.2 Speed 70±18.3 47.9±18.8 60.8±15.3 52.7±16.5 190±24.9 171.3±20.6 186.5±26.6 162.4±25.0 998±82 1025±76 1106±90 1024±95 Follow-up -18.1±18.3 -13.4±18.8 -27.9±15.3 -27.6±16.5 -49.0±24.9 -36.7±20.6 -48.5±26.6 -38.6±25.0 -226±82 -226±76 -294±90 -281±95 Change 0.003 0.020 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 pa -17.2 -19.7 -32.5 -31.2 -17.5 -19.8 -18.4 -19.5 -18.1 -18.4 -21.3 -20.8 MIPC (%) 4.3 1.8 -11.0 -9.7 4.0 1.7 3.1 2.0 3.1 3.4 0.2 0.7 MIPCD (%) 0.527 0.713 0.009 0.036 0.11 0.498 0.952 0.715 0.039 0.089 0.542 0.627 pb compared against mean weight loss of 21.5%, p < 0.05. N, Newton; kN/s, kilonewton/second; a p-value: absolute parameter change, p < 0.05; b p-value: MIPDC, MIPC is weight loss of 21.5%. FV, vertical direction; FAP, FML, horizontal directions; LRmax, maximal loading rate; MIPC (%) denotes Mean of Individual Percentual Changes. MIPCD (%) denotes the MIPC difference from mean LRmax (kN/s) FML (N) FAP2 (N) FAP1 (N) FV2 (N) FV1 (N) Parameter and after (follow-up) bariatric surgery (mean ± SD). Table 8. Ground reaction force parameters in level-walking at 1.2 m/s and 1.5 m/s gait speeds before (baseline) 61 2.16±0.88 2.89±0.98 1.5 4.79±1.26 1.5 1.2 3.71±1.55 3.05±1.01 1.2 2.30±0.91 1.5 3.79±0.97 1.5 1.2 2.95±1.08 Baseline 1.95±0.56 1.49±0.52 3.73±1.41 2.75±1.10 2.07±0.58 1.6±0.55 2.93±1.19 2.11±0.74 Follow-up Level-walking 1.2 Speed -20.3 -27.3 -29.9 -0.86±1.19 -0.70±0.55 -0.98±0.58 -0.67±0.52 -0.94±0.56 -2.6 -30.4 -23.1 -20.3 -27.6 -0.84±0.74 -0.96±1.10 -1.06±1.41 MIPC Change <0.001 <0.001 0.012 0.004 <0.001 <0.001 0.008 0.001 p down up down up down up down up Phase 1.42±0.51 1.95±1.68 2.72±1.30 3.77±2.42 1.51±0.56 2.20±1.62 2.01±1.10 3.13±2.14 Baseline 1.24±0.41 1.75±1.11 2.44±0.92 3.79±1.46 1.36±0.46 1.97±1.07 1.8±0.81 3.22±1.37 Follow-up Stair walking -0.20±1.11 -0.18±0.41 0.02±1.46 -0.28±0.92 -0.23±1.07 -0.15±0.46 0.09±1.37 -0.21±0.81 Change -7.9 -11.3 6.1 -10.9 -8.3 -7.5 9.1 -15.2 MIPC 0.216 0.273 0.251 0.995 0.273 0.191 0.252 0.893 p value: significant differences in MIPC, p < 0.05. xy, horizontal direction; g, gravitational acceleration, 1g ≈ 9.81 m/s 2; FV, vertical direction; FAP, FML, horizontal directions; N, Newton; p- MIPC (%) denotes Mean of Individual Percentual Changes. IPA, initial peak acceleration; PP, peak-to-peak acceleration; z, axial direction; PPxy (g) PPz (g) IPAxy (g) IPAz (g) Parameter walking up and down before (baseline) and after (follow-up) bariatric surgery (mean ± SD). Table 9. The skin mounted accelerometer parameters at knee joint in level-walking at 1.2 m/s and 1.5 m/s gait speeds and in stair 62 63 Figure 7. The effect of BMI on the knee joint initial peak acceleration and peak-to-peak acceleration. Both the knee OA and control subjects were divided into three BMI (kg/m²) groups: BMI < 25, 25 ≤ BMI < 30, and BMI ≥ 30. The two-way ANOVA, *p < 0.05, **p < 0.01, N= numbers of subjects. 5.4 EFFECTS OF WEIGHT LOSS ON PHYSICAL FUNCTION 5.4.1 Questionnaires The stiffness and function scores, but not the pain scores improved 52.1% (p < 0.05) and 30.5% (p < 0.05) after bariatric surgery in the follow-up measurement, respectively (Figure 8) (Paper II). Four obese knee OA subjects reported mild knee pain. After bariatric surgery, the physical functioning, physical role functioning and general health domain scores improved in the post-operative situation by 28.2% (p < 0.001), 44.2% (p < 0.05) and 18.8% (p < 0.05), respectively (Figure 9) (Paper II). No significant differences were found in RAND-36 domain scores after bariatric surgery between knee OA and non-knee OA groups (data not shown). 64 Figure 8. Womac scores in millimeters (mm) (mean ± SD) in subjects with knee OA (n=6) before (baseline) and after (follow-up) bariatric surgery. Wilcoxon non-parametric test, *p < 0.05. 65 Figure 9. RAND-36 test results (mean ± SD) in subjects (n=16) before (baseline) and after (follow-up) bariatric surgery. Wilcoxon non-parametric test, *p < 0.05, ***p < 0.001. 5.4.2 Physical function tests The results of the physical function tests between the pre- and post-operative situation are presented in Figure 10 (Paper II). The physical function of obese subjects improved significantly (p < 0.05) in TUG, sock, stair descending and six-minute walk tests, but did not change in the stair ascending test and repeated sit-to-stand test after bariatric surgery induced weight loss. The TUG test took 14.3 % less time in the follow-up measurement compared to the baseline measurement. The subjects were better at putting on the sock on both right and left legs; success rates were 70.8% and 64.8 % better after bariatric surgery. The performance in the stair descending test result was found to be 13.8% better in the follow-up measurement than at baseline. The subjects walked a 12.1% longer distance in six minutes in the follow-up measurement. 66 When comparing the knee OA group and the non-OA group, only the stair descending test at the baseline and the repeated sit-to-stand test at the follow up measurements were significantly (p < 0.05) better in the non-OA group. Figure 10. Physical function tests (mean ± SD) in subjects (n=16) before (baseline) and after (follow-up) bariatric surgery. Student’s paired sample t-test and Wilcoxon non-parametric test, *p < 0.05. 5.4.3 Muscle composition The results of the composition of QFm are presented in Figure 11 (Paper II). After bariatric surgery, the absolute muscle thickness (cm) of RF, VL and VM decreased by 25.7 % and 25.2 %, 15.8 % respectively and the corresponding reductions in CSA (cm²) were 21.3 %, 67 15.2 % and 26.6 %. The ratio of muscle CSA/total body weight in thigh muscles revealed no statistical differences between the pre- and post-operative situation. The thickness of subcutaneous fat was reduced significantly at all measurement sites after bariatric surgery. RF and VM, but not VL muscle compartments of the QFm, indicated significantly (p < 0.05) more heterogeneity after bariatric surgery. The QFm composition and size were similar in the knee OA group and non-OA group except for the statistically (p < 0.05) thinner absolute muscle thickness of VL in the knee OA group after bariatric surgery. Figure 11. The composition of the quadriceps femoris muscle (QFm) (mean ± SD) characterized by QFm thickness (cm), subcutaneous fat thickness (cm), muscle cross sectional area (CSA) (cm²), muscle composition (gray scale) and the ratio of the CSA/total body weight (cm²/kg) in subjects (n=16) before (baseline) and after (follow-up) bariatric surgery. The 68 muscles are RF rectus femoris, VM vastus medialis, and VL vastus lateralis. The Student’s paired sample t-test, *p < 0.05, ***p < 0.001. 5.5 POSTURAL STABILITY IN KNEE OSTEOARTHRITIS 5.5.1 Postural stability The MSV, VAAP, VAML, SDCOPAP, SDCOPML and EA parameters did not differ statistically during bipedal stance with eyes closed and open between knee OA patients and control subjects. Furthermore, the balance parameters did not differ significantly between the radiographic OA subgroups while adopting a bipedal stance. Only EA values during bipedal stance with eyes open were found to be 40.8% (p < 0.05) higher in the knee with the higher OA grade (K-L 4) compared to knee with the lower OA grade (K-L 1) (Paper V). MSV, VAAP, VAML, EA or SDCOPAP, SDCOPML, ARD and MF parameters did not differ between knee OA patients and controls, who could maintain monopedal stance for 5, 10 and 30 s. The knee OA severity did not affect the MSV, VAAP, VAML, EA, SDCOPAP, SDCOPML, ARD and MF parameters while keeping a monopedal stance (Paper V). The values of fbalance,mean and fbalance,med in the AP and ML directions revealed no differences between the OA and control groups during bipedal and monopedal stance. The very high frequency in the AP axis in monopedal stance was found to be statistically 40.8% lower in knee OA subject than in their controls, but other PSD estimates did not differ between the groups. The radiographic OA subgroups exhibited no statistical differences in the PSD estimates. Furthermore, the disease severity in the leg did not affect the balance parameters except at the very low frequency in the AP axis, which was found to be 20.5% higher in the more diseased leg than in the healthier leg (Paper V). 69 5.5.2 Muscle activation during standing The RMS for EMG amplitude, fEMG,mean and fEMG,med in VM and BF muscles demonstrated no statistical differences in monopedal stance, but the values of fEMG,mean and fEMG,med in VM and BF muscles in the contralateral leg were found to be 16.3% and 13.2% (p < 0.01) higher and 19.2% and 19.5% (p < 0.05) lower in knee OA patients compared to controls (Figures 12 and 13) (Paper V), respectively. The RMS values for EMG amplitude and the values of fEMG,mean and fEMG,med in VM were demonstrated to be 55.6% higher (p < 0.05) and 47.9% lower (p < 0.05) in knee OA patients when compared to controls during bipedal stance with eyes open (Figures 12 and 13) (Paper V), but there were no significant differences when the eyes were closed. The RMS for EMG amplitude and fEMG,mean and fEMG,med in BF with the bipedal stance with eyes open or with them closed did not differ between groups. The differences in the RMS for EMG amplitude values between the groups for the time period of 5 s and 10 s were identical to the results achieved when the test duration was 30 s. 70 Figure 12. EMG activity in biceps femoris (BF) and vastus medialis (VM) muscles in knee OA and control subjects during measurements of postural stability. Mean and median EMG frequencies (fmean and fmed, (fEMG,mean and fEMG,med in the text)) were calculated. Without any affix = monopedal stance with eyes open, co = contralateral leg while maintaining a monopedal stance, eo = bipedal stance with eyes open. MANOVA, *p < 0.05, **p < 0.01. 71 Figure 13. EMG activity in biceps femoris (BF) and vastus medialis (VM) muscles in knee OA and control subjects during measurements of postural stability. Root mean square (RMS, muscle activity %) for EMG amplitude. Without any affix = monopedal stance with eyes open, co = contralateral leg while maintaining a monopedal stance, eo = bipedal stance with eyes open. MANOVA, *p < 0.05. Knee OA severity (K-L 1-4) did not affect significantly BF muscle activity during monopedal and bipedal stance with eyes open or closed. However, RMS for EMG amplitude during bipedal stance both with eyes open and eyes closed and the values of fEMG,mean and fEMG,med of motor unit activity during bipedal stance with eyes closed in VM differed significantly (p < 0.05 – p < 0.01) between the knee OA subgroups (Figures 14 and 15) (Paper V). The RMS values were greatest when the K-L grade was 3-4 whereas the values of fEMG,mean and fEMG,med were greatest when the K-L grade was 1-2 (Figures 14 and 15) (Paper V). The EMG activity results were identical to the results when the knee OA patients were divided into three subgroups (K-L 2-4) according to the K-L classification. The RMS and the values of fEMG,mean and fEMG,med of motor unit activity in VM and BF muscle 72 revealed no differences between the more diseased leg and the healthier leg during monopedal stance. The fEMG,mean and the fEMG,med of motor unit activity in BF in the contralateral leg were found to be significantly (p < 0.05) lower in the more diseased leg than in the healthier leg. Figure 14. EMG activity in biceps femoris (BF) and vastus medialis (VM) muscles in knee OA subjects divided into four subgroups according the radiographic severity of their knee OA (K-L 1-4, Kellgren-Lawrence 1-4) during measurements of postural stability. Mean and median EMG frequencies (fmean and fmed, (fEMG,mean and fEMG,med in the text)). ec = bipedal stance with eyes closed. MANOVA, *p < 0.05. 73 Figure 15. EMG activity in biceps femoris (BF) and vastus medialis (VM) muscles in knee OA subjects divided into four subgroups according the radiographic severity of their knee OA (K-L 1-4, Kellgren-Lawrence 1-4) during measurements of postural stability. Root mean square (RMS, muscle activity %) for EMG amplitude. eo = bipedal stance with eyes open and ec = bipedal stance with eyes closed. MANOVA, *p < 0.05, **p < 0.01. 5.5.3 Postural stability correlations Postural stability did not display any significant correlation with the RMS for EMG amplitude, knee isometric muscle strength, knee pain and radiographic severity during either bipedal or monopedal stance (Paper V). 74 6 Main findings and discussion 6.1 STUDY POPULATION The design was one of the strengths of Experiment 1. Control subjects were randomly selected from the population register of over 10000 candidates and the knee OA subjects were selected based on clinical criteria for uni- or bilateral knee OA as recommended by the American College of Rheumatology (131). In order to maximize the likelihood of obtaining subjects free of knee OA as well as subjects with knee OA, plain radiographs were taken from both knees in knee OA patients and also from the healthy controls. It was hoped to reduce the possible influences of the confounding factors by adopting predetermined and strict exclusion criteria. Although the knee OA subjects had higher weights and BMI values than the healthy controls, there were no significant differences in the muscle thickness or in the thickness of the subcutaneous fat (9). In addition, the body weight was applied as a covariate when analysing the results, so the effect of weight was minimized (Paper V). In Experiments 2 and 3, the number of subjects was small (n=18 and n=15-16). However, inter-group comparisons are not necessary in these kinds of study designs, since the parameter changes between the measurements are compared on an individual basis. If one wishes to obtain a representative profile of gait, it is more important to gather a sufficient number of gait cycles for each subject rather than to measure a large number of subjects (Papers III, IV). In Experiment 3, the study population included only a few men and pre- and postmenopausal women in different age categories, and thus the results of this study may not be generalizable to all obese populations. On the other hand, the physical function measurements were diverse involving several objective and subjective physical function tests, which make it possible to evaluate many different phenomena related to bariatric surgery induced weight loss (Paper II). 75 In Experiment 3 (Papers II and IV), the study population was measured in the follow-up period of 8.8 months after they had undergone bariatric surgery. A prospective ten year study has been shown that the maximal weight loss has been observed one year after bariatric surgery, though the greatest weight loss occurred during the first six months (241). It can be claimed that the weight loss at 8.8 months after bariatric surgery, as conducted in this study, is nearly the maximal weight loss that will be attained after surgery. This is confirmed by comparing the present losses at the 8.8 months’ follow-up period to the weight losses seen at 0.5 and 1 year follow-up periods in the study of Sjöström et al. (241). 6.2 REPEATABILITY OF ACCELERATION AND EMG MEASUREMENTS The test–retest repeatability of IPA, RMS and ATRmax accelerations was demonstrated to be acceptable in the axial direction during level walking and walking up stairs in healthy subjects, but only the RMS accelerations during level walking exhibited good repeatability in knee OA subjects, a result in agreement with the study of Turcot et al. (186). The PP acceleration in the resultant axial as well as in the resultant horizontal direction have exhibited good repeatability (CV <15%) in healthy subjects (24). Although the RMS value is relatively simple to use and it seems to be the most constant parameter, it is not necessarily sensitive enough to be able to neglect the large individual variations and might therefore overlook the true impulsive loading rate. Furthermore, in knee OA patients, the RMS acceleration could disregard the effects of symptom variation between test and retest sessions, because the RMS is considered as a calculatory value. Conversely, peak accelerations, e.g. IPA, could have greater possibilities to reflect the knee OA gait pattern, because they are more sensitive parameters, although they do not appear to be as stable as the RMS acceleration. The peak accelerations are believed to permit a better indication of the distinctive variations in acceleration, e.g. possible fluctuations in knee OA symptoms 76 such as those due to knee pain. This could partly explain the poor repeatability of peak accelerations in knee OA patients noted in this study. The knee joint moments and ground reaction forces, which would have provided a more comprehensive description of walking, were unfortunately not assessed. In addition to different parameters, it is also possible that some confounding factors affect the repeatability, which then impacts on the consistency of measurements. There are several factors that can influence the repeatability of normal gait analysis including variations in gait speed, number of analysed gait cycles, stair inclinations and the use of footwear (136,141). It has been recommended that in order to obtain reliable results in gait studies, one should undertake at least two, preferably more, trials (242). In this thesis, the gait measurements were performed in two different environments, the clinic and the gait laboratory and under two different conditions, level walking and stair walking. In the laboratory, the walkway made it possible to measure one gait cycle with two consecutive steps on the force platforms. In the clinic, it was possible to measure 3 gait cycles with 6 consecutive steps for each subject during level walking and five consecutive gait cycles during stair walking. It is not possible to identify all the confounding factors that might influence repeatability in gait analysis. However, every effort was made to standardize the conditions between the test and retest situations, i.e. maintaining the same study personnel and environment, instruments, recorders of the measurements, but it is possible that the individuals being tested could have experienced a learning effect. Thus, the same test leader instructed the subjects and carefully carried out the testing procedure and two trained researchers prepared carefully the subjects prior to the measurements e.g. the SMAs and EMG electrodes were attached tightly to the skin. At least one study has indicated that the same individual need not conduct all testing sessions in order to obtain reliable results (185). The SMAs and EMG electrodes might shift slightly on the skin and this could contribute some variation into the results. An attempt was made to minimize this possibility with each subject wearing tight-fitting spandex trousers and a shirt to 77 facilitate the installation and testing of equipment. Plain shoes without any dampers on the sole were used to avoid variations due to shock-absorbing footwear. It was tried to diminish any possible learning effect by allowing the subjects to adequately familiarize themselves with the testing procedure and equipment. The gait speed has been shown to influence most of the biomechanical parameters of gait in healthy subjects, and also in patients with OA, and therefore it is important to control the gait speed (25,136,243,244). Constant gait speeds of 1.2 m/s and 0.5 m/s were used for level and stair walking, respectively, which are reasonable approximations of the normal gait speed of the study groups (141,245). Zeni et al. (246) reported that a noncontrolled, self-selected gait speed caused differences in gait parameters and affected muscle activation in knee OA subjects, but this problem was not encountered when gait speed was controlled. In the present study, the severity of disease was variable (the knee OA group included KL grades from 2–4), which means that there might have been extensive variation in the structural progression of the disease and this could be anticipated to lead to changes in the manner of walking; this might explain, at least in part, the poor repeatability of IPA and ATRmax and the non-acceptable repeatability of the EMG measurements. Another explanation for poor repeatability could be the fluctuations in knee OA pain symptoms, although the knee pain was mild in knee OA subjects during the first testing session. It has been reported that the severity of knee OA itself does not exert a major effect on gait when the gait speed is kept constant (25). On the other hand, Astephen et al. (247) reported that gait and neuromuscular pattern differences did progress as a function of knee OA severity when using a self-selected walking speed. Rutherford et al. (248) reported that an increasing level of knee OA severity affected the specific amplitude and temporal knee joint muscle activation patterns in a systematic manner when the subjects had a self-selected walking speed. Therefore in the present experiments, the gait speed was pre-determined and kept constant in each testing session. Further, the gait parameter changes were compared individually, so the use of a constant speed did permit a reasonable comparison between the test and re-test measurements, and thereby 78 eliminated the potential effects arising from different gait speeds. In addition, the selected gait speeds for level and stair walking were achievable and suitable for all knee OA and healthy subjects. SMA was attached below the knee joint because the soft tissue thickness is generally small in this area even in individuals with a possibly high BMI. Further, there is evidence that the reliability of loading measurements (e.g. IPA and PP) conducted below the knee is better than the corresponding SMA placed above the knee, where the soft tissue beneath the SMA is obviously thicker, since this might cause vibration and other soft tissue artefacts in the SMA sensor, causing variation in reliability (24). The poor repeatability of IPA and ATRmax in knee OA patients could partly be explained by the change in gait style provoked by knee pain, which might cause more vibration in the SMA sensor between testing sessions. In addition, the actual peak acceleration, i.e. IPA and ATRmax values in knee OA patients were higher than in healthy ones. The higher impact loading could contribute some vibration to the sensor, resulting in lower reliability in the measurement of certain loading parameters (24). The findings revealed a reasonable repeatability of EMG measurements, depending on the measured muscle, during level and stair walking in healthy individuals, but not in knee OA subjects. There have been no published studies on the repeatability of surface EMG in stair walking in healthy subjects, and only one study has investigated a knee OA population (194). In contrast to the present study, Hubley-Kocey et al. (194) detected good to excellent ICC2,k values for PP scores and CCI values in EMG recordings in the lateral and medial gastrocnemius, VL and VM, RF, medial and lateral hamstrings with subjects walking at a self-selected gait speed. However, both the measured EMG parameters and also their study population were different from those in this study. Only men with knee OA were included in the present study, while Hubley-Kocey et al. (194) investigated both men and women. In addition, there were differences in some of the clinical characteristics of the subjects (e.g. BMI values and WOMAC pain level). Thus, no direct comparison can be made between the results of these two studies. 79 The EMG activity of individual muscles is dependent not only on walking speed, age, and body size, the measured muscle and study protocol but also on a number of technical factors inherent in EMG collection. The process of recording the EMG signals is frequently considered as the main source of measurement error. Although there is rather comprehensive use of EMG in the clinic, there is still discussion about the advantages of the different recording electrode types. The most commonly used surface electrodes are non-invasive and enable recording over a large muscle area, but cannot register the deep muscles. Despite this weakness, it has been reported that the reliability of surface electrodes for evaluating EMG activity of lower limbs is adequate and no worse than can be achieved with intramuscular electrodes (195,249). The other problem concerns the inclusion of signals or crosstalk from neighbouring muscles during contraction (250). In an attempt to diminish these problems, the skin area was well shaved and alcohol-washed to ensure low inter-electrode impedance (<5 kΩ). Cross-talk between the muscles was presumed to have only minimal effects on EMG signals because of the relatively small IED (251). In addition the relatively large recording area of the electrode poles could have had effects on EMG signals. By utilizing the normalized signal, as done in this study, it is possible to eliminate the sources of amplitude differences e.g. skin resistance, presence of subcutaneous fat, distance from motor units, and it is also possible to undertake amplitude comparisons across subjects for the same muscle in test and re-test sessions (195). In this study, EMG was normalized to the activation estimate of the maximum EMG signal obtained during walking up stairs at 0.5 m/s, which would take reflex functions into account, although according to Burden et al. EMG normalization to the maximal isometric voluntary contractions is the best approach (252). This choice was made because among knee OA patients, knee pain could have interfered with the strength measurement and thus influenced the maximum EMG. This EMG normalization method is supported by the results of Benoit et al. (253), who demonstrated that methods of normalizing EMG to the maximum isometric contraction or to the maximum EMG amplitude during gait were equivalent in patients with anterior cruciate ligament injuries. Furthermore, Murley et al. 80 (193) reported that normalizing EMG to the value of very fast walking produced less variability between participants among all EMG amplitude variables compared to maximal isometric voluntary contractions and un-normalized values. There are multiple options from which to choose a reliability parameter. The selection of the statistical parameters depends on the study protocol, especially on the studied parameters. Furthermore, the biological variation within the study group will affect the reliability. Two different statistical parameters were used to evaluate repeatability in this study. ICC2,k was chosen, because it is appropriate for two-way random average measures and it is content specific (240). ICC describes the relative reliability, which describes how strongly units of measure in the same group resemble each other (254). The relative nature of the ICC reflects the dependence between the magnitude of an ICC and the between-subject variability; this means that if subjects are slightly different from each other, ICC values will be small, even if trial-to-trial variability is low (240). On the other hand, if subjects greatly differ from each other, ICC values can be high, even in cases when the trial-to-trial variability is high. Due to the natural weaknesses of the relative reliability measures, the CV was chosen to reflect absolute reliability, since this parameter describes the degree of variability of repeated measurements in relation to the mean of population (254), e.g. the less they vary, the higher the repeatability (184). 6.3 EFFECTS OF OBESITY AND WEIGHT LOSS ON JOINT LOADING Most of the absolute GRF parameter values decreased after the weight loss, as hypothesized. The ML GRF parameter values diminished more than would be predicted simply according to the weight loss. The values of knee acceleration parameters decreased, which meant that there were reductions in the impulsive loading values, reflecting a more 81 gentle ground contact. The values of SMA parameters did not change in stair ascent and descent. Similar to Browning and Kram (206), the absolute rather than normalized values of the GRFs were used, because the joint articulating surface area is not proportional to body weight and the absolute values reflect the actual joint loading. The results of vertical (FV1) and AP (FAP1) GRFs at the 1.5 m/s gait speed (20.8% and 19.5% decreases following a 21.5% weight loss) in this study are quite consistent with the values reported by Hortobagyi et al. (21), who found 27.6% and 23.8% reductions in FV1 and FAP1 values after average weight loss of 27.2%. While the vertical and AP GRFs reduced nearly proportiontely to weight loss, the ML GRFs decreased (32.5% (1.2m/s) and 31.2% (1.5m/s)) more than would have been expected according to mean weight loss (21.5% decrease), likely due to narrower step width at the follow-up measurement. Browning and Kram (206) have reported consistent findings with this study. These authors demonstrated a greater ML GRF and step width in obese subjects compared to non-obese individuals (206). After radical weight loss, the narrower step width could be sufficient to improve postural balance in gait, although a larger step width would be expected to produce greater postural stability and prevent falls in obese subjects (255). Elevations of 0.5 to 1.0 g in the amplitudes of baseline knee axial SMA parameters (IPAz and PPz) during level walking were observed in this study compared with the amplitudes stated in an earlier study with healthy individuals (25). However, the significant decrease of 0.8 g in knee IPAz at 1.2 m/s and 1.5 m/s gait speeds after bariatric surgery produced amplitudes comparable to those found by Liikavainio et al. (25). The horizontal SMA parameters (IPAxy and PPxy), which express the impulsive shear forces and which have been stated to be damaging to articular cartilage (12), were also determined, but no differences were detected between the magnitudes of impulsive shear accelerations and the magnitude of axial counterparts in level walking, and furthermore there were analogous trends between horizontal knee SMA parameters and IPA z. 82 Biomechanically, muscle forces act as the major determinant of load distribution across the joint surface and thus any reduction of this action of the muscle forces, will eventually change the joint loading conditions (256). Another protective mechanism against potentially harmful impulsive loading of the musculoskeletal system may be the activation of QFm before the heel strike during walking (24,257). The poor physical capacity (6) and weak muscle strength (258,259) in obese individuals might impair the ability of their neuromuscular system to reduce the generation of this shock wave. On the other hand, Stegen et al. (260) detected a notable decrease in dynamic and static muscle strength of QFm after bariatric surgery. Hue et al. (261) reported that this loss of muscle strength was well tolerated due to the improved association between force and body mass and the ability to maintain that force had been conserved. In this study, the different gait strategy might explain the acceleration changes after bariatric surgery, if the QFm strength had been preserved. The finding of the less forceful loading of the lower extremities during walking in obese subjects after weight loss may have clinical significance in the prevention of knee joint degeneration. The excessive impulsive forces impacting on the knee joint have been postulated to trigger the initiation and progression of knee OA (25,61,164). Radin et al. (164) claimed that so-called pre-osteoarthrotic patients with occasional activity-related knee pain exhibited higher axial tibial accelerations, e.g. higher impacts at heel strike, compared to their healthy counterparts. It has also been shown in healthy young subjects that there is a high impulsive load at a normal gait speed at heel strike (166). Chen et al. (262) demonstrated that Chinese women load their lower extremities less forcefully than Caucasian women, which could be one factor explaining the lower prevalence in knee OA in Chinese females. In contrast, some authors have disputed this hypothesis and do not believe that the impulsive forces during strike are involved in the progression of knee OA, i.e. there are studies where no difference has been detected in impulsive vertical GRF or peak accelerations at heel strike between elderly knee OA subjects and their healthy 83 controls (23). However, the effect of impulsive loading on the incidence of knee OA still remains open because of the cross-sectional study designs. 6.4 EFFECTS OF WEIGHT LOSS ON PHYSICAL FUNCTION AND COMPOSITION OF QFm The obese subjects exhibited improvements in their objectively measured physical function after bariatric surgery induced weight loss, as hypothesized. Furthermore, the RAND-36 survey revealed that obese subjects assessed that their physical functioning, physical role functioning and general health domain scores of the HRQOL had improved in a statistically significant manner after bariatric surgery. When comparing those obese subjects with knee OA to those without knee OA, it was found that the stair descent at baseline and the sit-to-stand test at follow-up exhibited to be in the non-knee OA group. The WOMAC scores after bariatric surgery revealed that obese knee OA subjects experienced improvements in their scores for stiffness and function, but not for pain. The results of objectively measured physical function tests are in parallel to those reported in previous studies (15,16,45,50). These studies demonstrated that the bariatric surgery induced weight loss had positive effects on the objectively measured physical function from 3 weeks to 12 months after surgery. A battery of validated tests for physical function, which could be practically applied in general practice, was used in this study. In addition, the test battery was intended to assess the normal daily activities. Although the objective physical function improved in this study, the improvements appeared to be rather small and there was only a minor percentage difference in the result between baseline and follow-up measurements. Therefore, one can only speculate on the clinical importance of these findings. In this study, the obese subject did not necessarily have to perform at her/his maximal best in the physical function tests, e.g. the sit-to-stand and TUG tests might be too 84 easy to perform in these obese subjects who had a mean age of 45.1 years. These kinds of tests are mainly used in examinations of elderly subjects (263-265) and definitive normative reference values for younger age-groups and obese subjects are lacking. Furthermore, it is possible that by prolonging the duration of these types of tasks to several minutes or by undertaking measurements of muscle strength instead of performance tests, it would have been possible to detect more marked differences in physical function. It has to be also considered that the increased muscle fat and connective tissue proportion and decreased muscle thickness after bariatric surgery might partly explain the minor changes in objectively measured physical function tests. However, an obvious difference was exhibited between the healthy subjects of the same age (age group 40-49 years) and the obese subjects of this study in terms of walking distance in the 6minute walk (at the baseline and follow-up in this study mean distance 501m (57 SD) and 561m (51 SD) based on the reference values (mean distance 611 m (85 SD)) (266). After bariatric surgery, the muscle and fat thickness and muscle CSA were found to be statistically significantly lower, the proportion of fat and connective tissue higher in QFm, but the ratio of CSA/total body weight in the measured part of QFm remained unchanged. One important result of this study was that the major weight loss achieved after bariatric surgery reduced both the fat mass and the fat-free mass. This is an undesirable situation, because weight loss, especially among the elderly, if accompanied by a loss of fat-free mass could have potentially disastrous effects e.g. diminished functional capacity and altered metabolic function of the muscle tissue (58). The results of this study are in accordance with those of Pereira et al. (59), who also detected a decrease in the muscle and fat thickness of the QFm after bariatric surgery. However, they did not evaluate the composition of QFm. In the present study, the increased muscle fat and connective tissue proportion in connection to the decreased muscle thickness after bariatric surgery might be one possible explanation why only minor improvements were observed in the physical function tests. The ratio of CSA/total body weight of QFm did not change after bariatric surgery, which was not an unexpected result, as the muscle size of 85 the QF is generally adjusted to the total body mass. Since the total body mass fell precipitously and no extensive additional exercise training was provided, the absolute CSA of the QFm diminished as well. In earlier studies, several investigators have also reported that there is mainly fat loss with a relative preservation of muscle mass after bariatric surgery based on restrictive surgical techniques, which cause slower and lesser degrees of total body weight loss (55,56). Furthermore, the provision of extra physical activity plus a weight loss intervention program (53) or increasing the amount of aerobic exercise (58) have shown some association with decelerated muscle mass loss. No special exercise program was provided in the present study. It could be postulated that some kind of physical activity might have diminished the loss of lean body mass during the weight loss intervention. For example, Stegen et al. (260) demonstrated that combined exercise and resistance training could prevent the decrease in muscle strength or even increase muscle strength, although the weight loss after bariatric surgery had induced a fat-free mass loss and decreased dynamic and static muscle strength. There is also evidence that long-term muscle training can maintain the muscle architecture and replace fat tissue with muscle tissue, in other words, reducing the proportion of fat in the muscle tissue in normal weight subjects (224,267). 6.5 POSTURAL STABILITY IN KNEE OSTEOARTHRITIS No significant differences were found in postural stability between knee OA subjects and healthy controls and between knee OA subgroups nor were any differences detected between the more diseased leg and the healthier leg in knee OA subjects. In contrast to these results, previous studies have described an increased postural sway in knee OA patients when they have been compared to healthy subjects (8,118,268,269) and also between knee OA subgroups where there were more balance control deficits in those patients with moderate to severe knee OA than in patients with mild knee OA (120). 86 Many different balance tests have been designed, but there is no standardized, single method with which to assess the overall integrity of the balance control system. Thus, the variability of results in postural control measurements in different studies might be due to different measurement techniques (8,118,268-270). It can be speculated that evaluating postural stability while standing with both legs on the floor with eyes open and closed and standing on one leg with eyes open are suitable but relatively simple methods. Thus, it would be important also to assess postural balance under more difficult conditions, for example using an experimental arrangement to mimick muscle fatigue, because it has been reported that muscle fatigue can influence the control of posture (271,272). On the other hand, many aspects such as vision, proprioception and sensing by the inner ear are utilized in balancing the body position. Thus, postural imbalances can be induced by deficits in visual, vestibular, or proprioceptive systems, and these deficits are not necessarily displayed by knee OA patients. The evaluation of postural control could be disturbed by the overlapping functions of different inputs in the postural control system. The test conditions in this study may not have been able to adequately separate the recognized specific deficits. The balance parameters assessed in the very low frequency domains have been shown to associate with visual control, and these were not determined in this study. One can only speculate on whether the knee OA subjects’ visual acuity may have affected the results of this study. The function of vestibular system was minimized by ensuring that the laboratory was a noiseless environment. It is believed that impaired proprioception, which is present in knee OA subjects (273-276), can destabilize postural control. The knee OA patients with severe pain suffer from soreness, joint stiffness and rapid fatigue when they are forced to stand in an upright position. The severity of the pain could well associate more closely with impaired postural stability via proprioception; this might be better than only assessing the radiographicallyassessed severity of the disease. In the present study, the presence of pain did not seem to have any effect on the postural control, which is at odds with the earlier results of Hassan 87 et al. (118), who reported that the amount of knee pain was one important factor affecting postural control, although there is also evidence that knee proprioception did not improve after pain relief. In the present study, the amount of pain experienced by the knee OA subjects was rated as only mild, which might have affected the results. However, the fact that postural stability in knee OA subjects is not always related to pain shows that postural stability is influenced by many other factors. The muscle activity (RMS) was found to be significantly higher in knee OA patients than in their healthy counterparts during bipedal stance with eyes open, as hypothesized. The severity of knee OA also exerted an effect on muscle activity. The most severe grade of knee OA displayed an association with the highest muscle activity (RMS) in VM during bipedal stance with eyes open and closed. On the other hand, the firing frequency of motor units was found to be statistically higher in the controls compared to the knee OA subjects during bipedal stance with eyes open. The result of this study are similar in some respects to those described by Brucini et al. (277) and Hiranaka et al. (278); i.e. standing caused a higher recruitment of muscle fibres and higher activation level of QFm in subjects with painful knee OA in comparison to healthy controls. Brucini et al. (277) concluded that the muscle hypofunction and pain could be responsible for the differences in muscle activation in knee OA. The increased muscle activity seen in knee OA could also be a compensatory response to muscle weakness or joint laxity and might be an attempt to achieve a degree of joint stability by developing increased joint stiffness. 6.6 CLINICAL IMPLICATIONS FOR FUTURE STUDIES The lower impulsive loadings following intensive weight loss after bariatric surgery in level and stair walking could favorably alter the mechanical profiles of obese adults by attenuating the stresses experienced by cartilage and subchondral bone. This could exert a 88 positive influence on the emergence of new cases of OA, or at least possibly slow down the progression of the disease. Intensive weight loss is a clear treatment recommendation for knee OA since it is recognized as reducing the possibility of developing knee OA and it is also possibly able to slow knee OA progression. Longitudinal prospective studies in healthy and knee OA are warranted to demonstrate the effects of weight loss on these issues and to evaluate the preservation of achieved benefits. The improvements in objective and subjective physical function following weight loss after bariatric surgery were rather small, although the sock test, stair descending test and 6-minutes walk test were statistically significantly improved. These tests could be recommended as ways of assessing physical function in obese subjects. However, the muscle thickness and CSA decreased after bariatric surgery. It could be assumed that whereas light and intensive weight loss improve physical function, radical weight loss after surgery may lead to a more extensive loss of muscle mass, leading to only a slight improvement in physical function. Thus the optimal treatment strategies in obese adults should consider both the positive and the negative effects of weight loss. This indicates that it is important to incorporate muscle-building and exercise training programmes into weight loss interventions before, and especially after, bariatric surgery, increasing the possibility that one can have major fat mass loss without any loss of muscle mass. Further prospective studies will be needed to demonstrate the effects of muscle-building and exercise training interventions on physical function and muscle composition in obese patients who have undergone bariatric surgery. In general, SMAs and surface EMG measurements are repeatable methods in gait evaluation in healthy subjects. Further studies of repeatability are needed and these should focus on designing the optimal study protocol that would allow the generalisation of the findings from different study populations. This could be advantageous in the development of a more reliable and effective tool for diagnostics and rehabilitation in different pathological conditions affecting walking. 89 Although no postural stability deficit in knee OA subjects was observed in this study, postural stability should be evaluated and tested under more challenging circumstances in knee OA subjects and by using a study design which could evaluate multiple factors simultaneously such as proprioception and muscle strength, because excessively easy balance measurements may not necessarily reveal the potential changes and deficits in postural stability, especially in early stages of knee OA. 90 91 7 Conclusions The following main conclusions can be presented: 1. The overweight and obese subjects load their lower extremities more than lean individuals during initial ground contact during level walking. This increased knee joint loading could adversely change the mechanical and biomechanical profiles of obese adults by increasing cartilage and subchondral bone stress, making the knee joint liable to degeneration. 2. The weight loss achieved after bariatric surgery has a positive impact not only on physical function but also on the subcutaneous fat thickness of the QFm as well as the subjects’ perception of their health status. However, major weight loss does exert a negative effect on the QFm muscle thickness as well as on the CSA and the fat and connective tissue proportion of the QFm, reflecting possible changes in metabolic function of the muscle tissue. These alterations may possibly decrease the muscle strength and reduce the patient’s physical function. In addition, the present results emphasize the importance of assessing the obese subjects’ subjective and objective physical capabilities before they undergo bariatric surgery, emphasizing that avoiding body weight gain as well as losing body weight in obese may have a positive effect on objectively and subjectively measured physical function. 3. In level walking, all of the absolute GRF parameters decreased significantly after the bariatric surgery induced weight loss, reflecting the mass-driven changes in GRF in proportion to the weight loss. The weight loss also lowered impulsive accelerations at the knee joint level indicating that the subjects were making a more gentle ground 92 contact; evidence that there is mechanical plasticity in the gait after bariatric surgery induced weight loss. 4. SMAs provide a repeatable method for investigating accelerations during the initial foot contact in healthy subjects but not in knee OA subjects. 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