Kyphoplasty in the Treatment of Osteolytic Vertebral Compression Fractures as a Result of Multiple Myeloma By S. Dudeney, I.H. Lieberman, M-K. Reinhardt, and M. Hussein Purpose: We prospectively evaluated the safety and efficacy of kyphoplasty in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. The principle symptoms in multiple myeloma result from bone destruction, especially the spine. Kyphoplasty is a new technique that involves the introduction of inflatable bone tamps (IBT) into the vertebral body. The purpose of the IBT is to restore the vertebral body back toward its original height, while creating a cavity that can be filled with highly viscous bone cement. Patients and Methods: Fifty-five consecutive kyphoplasty procedures were performed in 18 patients with osteolytic vertebral compression fractures resulting from multiple myeloma. Cement leakage and any complications were recorded. Early objective analysis was made by comparing preoperative and latest Short Form 36 Health Survey scores. Height restoration was estimated by measuring vertebral height on lateral radiographs. Results: The mean age of patients was 63.5 years, mean duration of symptoms was 11 months, and mean follow-up was 7.4 months. There were no major complications related directly to use of this technique. On average, 34% of height lost at the time of fracture was restored. Asymptomatic cement leakage occurred at two (4%) of 55 levels. Significant improvement in SF36 scores occurred for Bodily Pain (23.2 to 55.4, P ⴝ .0008), Physical Function (21.3 to 50.6, P ⴝ .0010), Vitality (31.3 to 47.5, P ⴝ .010), and Social Functioning (40.6 to 64.8, P ⴝ .014). Conclusion: Kyphoplasty was efficacious in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. Kyphoplasty is associated with early clinical improvement of pain and function as well as some restoration of vertebral body height. J Clin Oncol 20:2382-2387. © 2002 by American Society of Clinical Oncology. ULTIPLE MYELOMA IS a tumor of B-cell origin. Estimates of bone involvement at presentation vary from 70% to 100% of patients. The principle morbidity in the disease is as a result of skeletal involvement, particularly the spine. Myeloma causes the resorption of bone by stimulating osteoclasts via osteoclast-activating factors.1 The present treatments for multiple myeloma include radiotherapy and chemotherapy to control the disease and bisphosphonates to deter bone destruction. Unfortunately, multiple myeloma is presently still incurable; however, survival rates are steadily improving. Myelomatous osteolytic destruction of the spinal column is common and has become more of a clinical issue with the prolonged survival rates. Typically, the diffuse involvement that occurs results in painful progressive vertebral compression fractures at multiple levels over time. Treatment with bed rest, bracing, and analgesics are the standard of care for most of these patients and have proven to be of limited benefit, especially when considering the progressive spinal kyphosis and its subsequent consequences. Cement augmentation of the vertebral body has been used for the relief of pain in the spine as a result of tumor involvement since it was first described by Gallibert in 1984.2 This technique of vertebroplasty involves the injection of low-viscosity liquid bone cement (poly-methylmethacrylate [PMMA]) into the damaged vertebral body via a percutaneous approach under image guidance. This technique has been shown to relieve pain in unstable vertebral fractures caused by tumor and in osteoporotic compression fractures. The difficulty with vertebroplasty as a technique is two-fold. It makes no attempt to restore lost vertebral height or correct the resultant spinal deformity. Deformity becomes more important when there is generalized spinal involvement as in multiple myeloma, with multiple fractures occurring over time. The second major difficulty is the very high incidence of cement leakage as a result of forcing liquid bone cement into the closed collapsed space of the vertebral body. The rates of cement leakage are reportedly from 30% to 60%.3-5 Neurologic compression after cement extravasation is a rare but potentially devastating complication. Pulmonary embolus of bone cement has also been reported.6,7 Open surgical decompression in combination with vertebroplasty or surgically controlled vertebroplasty has been advocated by some workers to overcome the difficulty of M From the Department of Orthopaedics and Minimally Invasive Surgery Center, Cleveland Clinic Foundation; and the Multiple Myeloma Program, the Cleveland Clinic Tausig Cancer Center, Cleveland, OH. Submitted September 21, 2001; accepted February 11, 2002. Address reprint requests to I.H. Lieberman, MD, Department of Orthopaedics, Minimally Invasive Surgery Center, 9500 Euclid Ave Desk A-41, Cleveland, Ohio, 44195; email: [email protected]. © 2002 by American Society of Clinical Oncology. 0732-183X/02/2009-2382/$20.00 2382 Journal of Clinical Oncology, Vol 20, No 9 (May 1), 2002: pp 2382-2387 DOI: 10.1200/JCO.2002.09.097 Downloaded from jco.ascopubs.org on September 9, 2014. For personal use only. No other uses without permission. Copyright © 2002 American Society of Clinical Oncology. All rights reserved. KYPHOPLASTY FOR MYELOMATOUS COMPRESSION FRACTURES 2383 leakage in vertebroplasty.8 This approach, however, defeats the purpose of a minimally invasive technique. Kyphoplasty is a relatively new technique for cement augmentation of the vertebra. It involves the placement of a trochar into the vertebral body posteriorly followed by the hand drilling of a bone channel in the vertebral body. This allows the passage of a balloon-like inflatable bone tamp (IBT) into the vertebral body. The inflation of the IBT under careful image guidance is designed to produce a cavity within the vertebral body and to restore lost vertebral height.9,10 The creation of the cavity within the vertebra is critical because it allows the insertion of very viscous, partially cured cement into the vertebral body. This is in contrast to the liquid state of cement used in vertebroplasty. The insertion of thick viscous cement into a preformed cavity has been shown to result in a lower rate of cement extravasation in patients with osteoporotic vertebral compression fractures.11 The aim of this study was to determine the safety and efficacy of the kyphoplasty procedure in patients with vertebral compression fractures secondary to multiple myeloma. Furthermore, we aimed to examine the rates of cement leakage, to look for evidence of height restoration and to compare preoperative and early postoperative pain and functional ability in treated patients. of biplanar fluoroscopy. This is followed by placement of a cannulated obturator over the guide wire. The obturator is then tapped into the bone over the guide wire. A working cannula is placed over the obturator and advanced until the tip of the cannula is seated in the posterior portion of the vertebral body. A hand mounted drill bit is then used to ream a tunnel in bone for the IBT to be passed through. The IBT is ideally situated under the collapsed endplate on the lateral radiograph. Inflation is slowly performed under fluoroscopy, as are all stages of guide wire, obturator, and cannula placement. The IBT inflation pressure is monitored closely during inflation via an in-line pressure gauge. Inflation is continued up to a maximum pressure of 220 psi or until the vertebral compression fracture has been reduced. Inflation should also be stopped if the balloon abuts the anterior, posterior, or side wall of the vertebral body. When a suitable cavity has been prepared and as much reduction is achieved as is possible, the PMMA cement augmented with barium is mixed. Smaller bone cement cannulae, which fit inside the working cannula, are prefilled with cement. Before its application, the cement is allowed to thicken. A 2-cubic cm bolus of cement is repeatedly suspended from a wooden spatula, and when the viscosity is such that the cement does not fall from the spatula, it is ready for injection. A 0.5 mL portion of cement is placed onto the drapes near the wound, and the radio opacity of the cement is confirmed before injection of material into the vertebral body. The bone filler cannula is then advanced through the working cannula to the anterior vertebral body wall, and cement is slowly extruded using a stainless steel stylet, which acts as a plunger. Filling is performed under continuous lateral fluoroscopic guidance. The use of the stylet and bone filler cannula enables cement to be applied at considerably higher viscosity than possible with injection through a 5-mL syringe and 11-gauge needle. Cement filling is stopped when the cement mantle reaches two thirds of the way back to the posterior vertebral body cortex on the lateral fluoroscopic images. The number of bone filler cannulae that need to be prepared is estimated from the final inflation volume achieved with the IBT. Often the volume applied is 1 to 2 mL greater than the final inflation volume, allowing cement from the central bolus to interdigitate with the surrounding cancellous bone (Figs 1 and 2). PATIENTS AND METHODS This study was designed as a single cohort using consecutive prospectively gathered data examining cement leakage, radiographic vertebral height restoration, and early outcome in patients with multiple myeloma after kyphoplasty as a treatment for osteolytic painful progressive vertebral compression fractures. Patients Measurement of Height Restored: Radiographic Assessment Fifty-five consecutive kyphoplasty procedures were performed in 18 patients with vertebral compression fractures resulting from multiple myeloma over 27 sessions. The mean age was 63.5 years (range, 48 to 79 years). The indications for kyphoplasty were vertebral compression fractures caused by myelomatous destruction causing pain and unresponsive to nonoperative modalities. Vertebral fractures that were unstable (by virtue of myelomatous destruction of the posterior elements ie, pedicles and facets, along with the vertebral body) or with retropulsed tissue or bone fragments were not considered for treatment with this technique. The mean duration of symptoms was 11 months (range, 0.5 to 24 months). Symptomatic levels were identified by correlating the clinical data with magnetic resonance imaging findings of marrow signal changes consistent with compression fractures. Magnetic resonance imaging was used to confirm the presence of a true wedge compression fracture and rule out burst type injuries with retropulsed bone. The vertical height of all fractured vertebrae were measured both pre- and postoperatively. Vertebral height was defined as the distance, endplate to endplate, at the center of the vertebral body on the lateral radiograph. The vertical height of the vertebra above the fractured vertebra was also measured to give an estimate of the height of the fractured vertebra before fracture. Calculations were made as follows: height regained ⫽ (posttreatment height ⫺ pretreatment fractured height); height lost ⫽ (estimated prefracture height ⫺ pretreatment fractured height); and the percentage of height lost that is now restored ⫽ (height regained/height lost) ⫻ 100. Multiple radiographs were standardized for magnification by measuring and comparing known landmarks to determine a magnification multiplier. The absolute values in height (mm) before and after treatment were statistically compared using paired nonparametric analysis (Wilcoxon signed rank test). Repeat measurements of the same vertebral levels after a 2-week interval with the same observer demonstrated an error of ⫾ 1.1 mm. Kyphoplasty Technique Assessment of Cement Leakage IBT placement involves identifying an extrapedicular or transpedicular entry point into the vertebral body using a guide pin, with the use Cement leakage was recorded prospectively at surgery. Postoperative radiographs were also examined for the presence of leakage of Downloaded from jco.ascopubs.org on September 9, 2014. For personal use only. No other uses without permission. Copyright © 2002 American Society of Clinical Oncology. All rights reserved. 2384 DUDENEY ET AL Fig 1. Steps in the kyphoplasty procedure (a) cannulation of the vertebral body; (b) placement of the IBT; (c) inflation of IBT and restoration of vertebral body height; and (d) resultant cavity and cement fill. cement. Cement leakage was recorded on the basis of position and correlated with any postoperative clinical symptoms. Measurement of Early Outcome: Clinical Assessment Outcome data was obtained by comparing preoperative and latest postoperative Short Form 36 Health Survey (SF36)12 data available at the time of analysis. Bodily Pain, Physical Function, Vitality, and the Social Function scores were selected from the SF36 profile before the study as they were deemed the most relevant with regard to the treatment of vertebral fractures in this population. Patients completed the SF36 questionnaire without assistance if feasible at the time of their preoperative assessment and at subsequent follow-up appointments at 1, 6, 12, 36, and 52 weeks. The Wilcoxon signed rank test was used for statistical analysis of SF36 data. A P value of less than .05 was deemed significant. RESULTS Patients and Levels All 18 patients tolerated the procedure well. The 55 levels treated ranged from T6 to L5, with the majority of treated levels at the thoracolumbar junction (T11, n ⫽ 9; T12, n ⫽ 7; L1, n ⫽ 8; and L2, n ⫽ 7). Twenty-seven percent of levels were at T12 or L1. Postoperatively, all patients were admitted to the 23-hour stay unit. Thirteen patients were discharged home the following morning; 11 were discharged that same afternoon. Three patients stayed for 2 or more days, all for medical/oncologic reasons unrelated to the kyphoplasty procedure. Safety and Efficacy At final follow-up, there were no major complications related directly to use of this technique, the IBT, or the use of PMMA bone cement. There were no injuries to spinal or extraspinal tissues as a result of guide pin, obturator, or cannula placement. IBT expansion was bounded by the vertebral body, and a cavity was created successfully in all cases. Downloaded from jco.ascopubs.org on September 9, 2014. For personal use only. No other uses without permission. Copyright © 2002 American Society of Clinical Oncology. All rights reserved. 2385 KYPHOPLASTY FOR MYELOMATOUS COMPRESSION FRACTURES Fig 2. Clinical example of kyphoplasty for myeloma; (a) collapsing vertebral body; (b) IBT restoration of vertebral height and anterior wall alignment; (c) and final cement augmentation. Cement Extravasation Cement extravasation was seen at two (4%) of 55 levels. A small volume of cement entered the epidural space in one patient. As soon as this was seen on the fluoroscope, cement application was stopped. In the second patient, a small tail of cement seeped through a sidewall cortical crack. No problems were identified clinically as a result of these extravasations postoperatively or at final follow-up. Height Restored Because of the nature of the osteolysis and resulting poor radiographs, height measurements were only possible in 39 of the 55 levels treated. In those measured, the mean central vertebral height lost was 7 mm (range, 2 to 17 mm). In seven levels (18%), there was minimal loss of height (ⱖ 2 mm) before treatment. In all 39 levels, the mean percentage of height lost that was restored by the procedure was 34% (range, 0% to 100%). In 12 levels (31%), there was no appreciable height restoration; at four levels, complete restoration occurred. In the remaining 23 levels (60%), there was a mean height restoration of 56%. SF36 Evaluation At a mean follow-up of 7.4 months, the SF36 scores for Bodily Pain, Physical Function, Vitality, and Social Functioning all showed significant improvement. Bodily Pain scores improved from 23.2 to 55.4 (P ⫽ .0008). Physical function improved from 21.3 to 50.6 (P ⫽ .0010). Vitality scores improved from 31.3 to 47.5 (P ⫽ .012). Social Functioning improved from 40.6 to 64.8 (P ⫽ .014). General Health, Mental Health, Role Physical, and Role Emotional scores did not show significant improvement. DISCUSSION In this phase I study, kyphoplasty was found to be safe and effective in the treatment of painful progressive osteolytic vertebral compression fractures resulting from myelo- matous destruction. Kyphoplasty resulted in a marked lowering in the leakage rate of cement compared with previous techniques involving cement augmentation of the vertebral body. On average, without stratifying for chronicity or configuration of fracture, we restored 34% of height lost at the time of fracture. In the vertebral bodies where height was restored, we restored on average 56% of height lost. We have previously examined the safety and efficacy of the kyphoplasty procedure for the treatment of vertebral compression fractures secondary to osteoporosis.11 In that cohort, we found a similarly low rate of cement leakage, a mean height restoration of 48%, and statistically significant improvements in early postoperative SF36 pain and function scores. Previous analysis of vertebroplasty has shown effective pain relief. In this current cohort, we found statistically significant improvement in bodily pain as measured by the SF36 (prekyphoplasty ⫽ 23.2, postkyphoplasty ⫽ 55.4, P ⫽ .0008). Every patient in this group recorded a sustained improvement in pain scores. These encouraging results are in contrast to more recent vertebroplasty reports that show at best a 50% improvement in pain scores in metastatic or myeloma patients13 Cortet et al14 performed vertebroplasty in 37 patients, 29 with metastases and eight with multiple myeloma. They achieved excellent pain relief but had a 72.5% leakage rate, with two patients requiring surgical nerve root decompression.14 Cotten et al15 examined vertebroplasty in a similar group of patients to show that pain relief was not related to percentage filling. It has been reported that between 4 to 8 mL of bone cement is estimated as the volume required to restore strength and stiffness in vertebroplasty.16 This is difficult to achieve with the vertebroplasty technique as evidenced by the significant risk of cement leakage. Symmetrical cement placement has also been suggested to be of importance.17 Downloaded from jco.ascopubs.org on September 9, 2014. For personal use only. No other uses without permission. Copyright © 2002 American Society of Clinical Oncology. All rights reserved. 2386 DUDENEY ET AL The short coming of this analysis is in the calculation and reporting of height restored. We have used a simple reproducible method that we have used in previous studies.11 In these myeloma patients, however, it can be difficult to fully differentiate the effects of bone osteolysis caused by tumor versus osteoporosis caused by medications and inactivity. In our previous study, we documented an intraobserver error of ⫾ 1.1 mm. We did document, on average, a 34% restoration of vertebral body height restoration, which is less than that documented in the osteoporotic group (48%). This analysis did not take into account chronicity of collapse or fracture configuration. It is our belief that the osteolysis caused by myeloma results in typically different fracture configurations (usually biconcave fractures) than those seen in true osteoporotic patients (usually wedge compression). Improving therapy and supportive care for myeloma and the probable increase in overall survival18,19 makes effective skeletal care of ever-increasing importance. Even though bisphosphonates have resulted in a significant decrease of skeletal morbidity,19 skeletal damage already sustained at the time of diagnosis as well as the pain resulting from these events limits mobility and, thus, increases morbidity and possibly mortality. The specific advantages of kyphoplasty are that it makes cement augmentation of the vertebrae a safer procedure and provides the opportunity for some restoration in height. The importance of cement leakage cannot be over emphasized. We advocate the use of biplanar fluoroscopy, with continuous screening during actual insertion of cement, and not computed tomography scanning as used by some workers for vertebroplasty. As with any new treatment, the main disadvantage is cost. The cost of kyphoplasty treatment may be offset by the decrease in morbidity, hospital stay, and pain management efforts related to spinal disease in myeloma patients. Kyphoplasty needs to be studied with a prospective economic evaluation of both treatment paths. Multiple myeloma is grossly a very soft vascular tumor, as evidenced by the backflow of blood from the working cannulae during kyphoplasty. The near fluid consistency of the tumor makes it easy for thick cement to displace it and results in impressive cement filling of the vertebra. The effects of dissemination of what is an already widespread disease is not known. We do not suspect any significant systemic effects and have not noted any in this initial group. We were also able to proceed safely with the kyphoplasty in all patients simultaneously with any chemotherapy, provided their WBC count was adequate and coagulation profile was normal. In other fracture types where the posterior wall is deficient, kyphoplasty is presently deemed unsuitable because of the risk of further displacement of bone fragments by the inflation of the balloon. Vertebroplasty has been used in these cases with some success in the past. In these instances, if open reconstruction is not considered appropriate, this may be an indication to consider vertebroplasty. Cement augmentation (vertebroplasty) has been used to treat other tumors including lung adenocarcinoma,20 multiple eosinophilic granuloma,21 and vertebral hemangioma.2,22 Kyphoplasty may have a role in the safe treatment of other disseminated lytic tumor types, and this is currently under investigation. Probably the most significant clinical issue when considering treatment for myeloma patients is the increasing survival time associated with improvements in chemotherapy. Nonetheless, by definition, all patients with multiple myeloma present with bone marrow involvement. The majority of morbidity and mortality is caused by skeletal failure because of bone destruction. Therefore, timely intervention of effective skeletal reconstruction is of everincreasing importance. Because we have gained experience with the technique and have witnessed the early and sustained clinical improvement in pain and function, we now advocate early treatment of any fractured or collapsing vertebral body. This philosophy should avoid the structural and debilitating functional effects of a progressive spinal kyphotic alignment. ACKNOWLEDGMENT We thank Kyphon Inc, Sunnyvale, CA, for providing the equipment and technical support for this study. REFERENCES 1. Callander NS, Roodman GD: Myeloma bone disease. Semin Hematol 38:276-285, 2001 2. Galibert P, Deramond H: Percutaneous acrylic vertebroplasty as a treatment of vertebral angioma as well as painful and debilitating diseases. Chirurgie 116:326-334, 1990 3. Watts NB, Harris ST, Genant HK: Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty. Osteoporos Int 12:429-437, 2001 4. Martin JB, Jean B, Sugiu K, et al: Vertebroplasty: Clinical experience and follow-up results. Bone 25:11S-15S, 1999 5. Ratliff J, Nguyen T, Heiss J: Root and spinal cord compression from methylmethacrylate vertebroplasty. Spine 26:E300-E302, 2001 6. 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Clin Rheumatol 13:518-521, 1994 22. Castel E, Lazennec JY, Chiras J, et al: Acute spinal cord compression due to intraspinal bleeding from a vertebral hemangioma: Two case-reports. Eur Spine J 8:244-248, 1999 Downloaded from jco.ascopubs.org on September 9, 2014. For personal use only. No other uses without permission. Copyright © 2002 American Society of Clinical Oncology. All rights reserved.