1. science
2. medicine
3. surgery
4. transplants

MYOSITIS
CLINICAL
FEATURES
OF
ROGER
From
The
clinical
OSSIFICANS
EIGHT
R. G. G.
SMITH,
the Nuffield
features
of treatment
with
Early correct
and because
diagnosis
myositis
PATIENTS
of eight
with
EHDP,
remains
unusual,
may be mistaken
THEIR
myositis
together
mainly because
for bruising,
RESPONSE
C. G. WOODS,
of Orthopaedic
patients
the diphosphonate
AND
and
RUSSELL
Department
PROGRESSIVA
OXFORD,
Surgery,
ossificans
with
TO
ENGLAND
University
progressiva
surgical
TREATMENT
of Oxford
are described
removal
of ectopic
the significance
ofthe
sarcoma
or mumps.
and the effects
bone,
assessed.
are
short great toes is unrecognised,
The diphosphonate
disodium
etidronate
(EHDP)
was given to all patients
in an attempt
to suppress
calcification
of new lesions;
in five
of them ectopic
bone was removed
during
the treatment.
EHDP
sometimes
delayed
the mineralisation
of
newly formed
bone matrix
after surgical
removal
but this delay could not be predicted.
The variable
effect
of EHDP
may
depend
Myositis
ossificans
dysplasia
ossificans
dominantly
It
also known
is a rare
is characterised
particularly
of
the
ossification
mainly
in
(Lutwak
1964; Illingworth
It produces
people
paper
a catastrophic
for which
summarises
of eight
patients
diphosphonate
the
toes
(EHDP),
and
an
illness
from
the region
increased
allowed
of the left elbow
passive
the patient
formation.
flexion
to feed
from
herself
5
by Mr J. Cockin,
to 35 degrees
and
again.
and
in young
and
the
effect
ethane-l-hydroxy-l,
inhibitor
Fleisch
which
of new bone
treatment.
This
and treatment
ossificans
disodium
1-diphosphonate
removed
skeletal
fingers,
and on the activity
connective
tissue
of
1971 ; McKusick
1972).
effective
features
myositis
(Francis,
and
absorbed
as fibrodisorder,
by
crippling
is no
clinical
with
Russell
the
and
there
the
of
on the amount
progressiva,
progressiva,
inherited.
abnormalities,
ectopic
muscle
particularly
1969;
of
calcification
Russell
and
Smith
1973).
PATIENTS
The clinical
features
are summarised
the eight
patients
had characteristic
The
malities.
plasma
alkaline
phosphatase
were normal
for age
ment
in all cases.
calcium,
inorganic
The
diphosphonate.
was demonstrated
precise
referring
I.
All of
abnor-
phosphate,
and urinary
total
hydroxyproline
at the start of diphosphonate
treateffects
of treatment
Table
II and amplified
in the text
phosphate
showed
the expected
with
this
in Table
phalangeal
are
shown
in
where
necessary.
Plasma
increase
on treatment
The term ossflcation
is used where
histologically;
otherwise
the less
term calcjfication
to radiographic
is employed,
appearances.
particularly
when
1-A
The
CASE
Cases
Smith,
1 and 2 have been briefly
Bishop,
Price and Squire
1-In
treatment
Case
day).
After
was
removed
recalcification,
Dr
Dr
Dr
48
excess
central
REPORTS
described
elsewhere
(Russell,
1972).
1970 this severely affected woman (Fig. 1) began
with oral EHDP
(20 milligrams
per kilogram
per
five
weeks
from
and
ectopic
the
right
a
larger
bone
calf.
piece
l#{149}5
centimetres
Radiographs
of
bone
in length
showed
was
therefore
no
I
FIG.
Case
radiograph
of the thorax
showing
skeletal
ossification.
excised
bone
osteoid.
vacuolation
There
showed
little
was patchy
and shrinkage
extensive
cellular
activity
atrophy
of fibres.
of
extra-
and
no
muscle,
with
The range
of
movement
did not decrease
and after five months
there was
no evidence
of recalcification.
She died of pneumonia
in
January
1971.
Post-mortem-Histology
showed
the cancellous
bone of the
vertebrae
and iliac crests to be grossly
osteoporotic;
osteoid,
present
consisted
on
just
of
only
a small
one
part
or
of
the
lamellae
two
Roger
Smith,
F.R.C.P.,
Consultant
Physician,
Nuffield
Orthopaedic
Centre,
Headington,
Oxford
0X3
R. G. G. Russell,
M.R.C.P.,
Medical
Research
Fellow,
St Peter’s
College,
Oxford,
England.
C. G. Woods,
F.R.C.Path.,
Consultant
Pathologist,
Nuffield
Orthopaedic
Centre,
Headington,
Oxford
THE
JOURNAL
OF
BONE
available
bone
(Paterson,
7LD,
OX3
AND
surface,
Woods
England.
7LD,
JOINT
England.
SURGERY
and
r4YOSITIS
OSSIFICANS
PROGRESSIVA
49
time of sampling.
Microscopic
areas
of fibre
bone,
only
a
proportion
of which
was calcified,
were seen in the scar tissue
at the site of operation.
Material
like cartilage
was also found
alongside
some
of the bone,
and
plump
osteoblasts
were
present
in some
of the surfaces.
Case 2-In
1962
C.
(Professor
sunlight
in an
1963 a series
patient
Dent)
attempt
was
and
to
of operations
and
occurred
after
the
left
attempts
hip
In April
again
1970
EHDP
on a vitamin
delay
ectopic
with
from
D-free
to keep
began
were
and
put
instructed
the right foot; recalcification
the operation
was repeated
from
of
this
F.
diet
away
from
mineralisation.
removal
In
of a bony
bar
occurred
after three months
in 1964.
In 1965 recalcification
made
to remove
bone
in front
the foot.
was
begun
in a daily
dose
of 200
milligrams
cellular
absence
later
three
(body
weight
51 kilograms).
This was increased
milligrams
after
four months,
and then to 1,000 milliin September
1970,
a week
before
ectopic
bone
was
from
the right foot.
Histologically
this showed
little
activity
and no excess
osteoid
(see Table
II).
The
of significant
calcification
in this region
six months
has been reported
previously
(Russell
ci’ a!.
1972),
and
years after the removal
of bone only slight recalcification
was
visible
to
400
grams
removed
continued
FIG.
2
appearance
1971.
The
Case 2-The
histological
the right biceps in April
structure
and
alised
interstitial
Morgan
there
1968).
is an
fibrosis
There
no
cellular
evidence
from
loss of
of
Elsewhere,
increased
3
FIG.
2. Figure
October
3-A
1971
FIG.
radiograph
showing
the
taken
extent
of bone
in July
1971 showing
removed
ten
days
the extent
VOL.
7
58-B,
No.
I.
FEBRUARY
976
radiograph.
milligrams
The
a day
dose
until
of
May
EHDP
1972
and
was
then
however,
calcification
or
recalcification
after
operation
occurred.
In March
1971 there
was an active
area
of myositis
in the right
biceps,
attributed
to trauma,
but no
radiological
evidence
of calcification.
Biopsy
about
a month
after the onset
of pain and swelling
showed
loss of striation
and
disintegration
of the sarcoplasm,
small
collections
of
round
cells and extensive
fibrosis
of interstitial
tissue (Fig. 2).
Early
calcification
was seen on the radiograph
three
months
later in July 1971.
Subsequently,
because
there was no evidence
of calcification at the site of the operation
on the foot, an attempt
was
made
by Mr J. Cockin
to remove
the bar of bone
in front
Generand eosin,
resorption
or formation.
A block
of tissue was removed
from
the region
of the operation
on the left elbow;
the ectopic
bone
in the muscle
was of two types.
Lamellar
bone,
away
from
the operation
site, contained
much
osteoid,
in some
places
five or six Iamellae
wide,
but the cellular
appearance
did not
suggest
excessive
rates
of deposition
or of resorption
at the
Case
the
reduced.
of muscle
removed
muscle
fibres show
area of round-cell
infiltration.
is present.
(Haematoxylin
..‘
170.)
was
on
at 1,000
4
ectopic
previously.
FIG.
bone
in front
Figure
of the calcification.
of the left hip.
5-A
radiograph
5
Figure
4-A
radiograph
taken
in February
1974
taken
showing
in
50
R. SMITH,
R. G.
G.
RUSSELL
AND
TABLE
CLINICAL
Age
Case
number
I
Date
of
Sex
birth
F
March
F
I
OF THE
EIGHT
PATIENTS
Operation
of
Unusual
features
5 years.
Treatments
EHDP
-
3 years.
Low
-
Swelling
hack
on
it.
D diet.
Avoidance
sunlight.
of head.
Progressive
Results
of
of
operation
bone
Swelling
on
hack of neck
1947
for
removal
myositis
August
Ci. WOODS
mode
of onset
1936
2
and
DF1AILs
C.
plus
EHDP
Comments
Two.
Recalcification
Grossly
Also extraction
of teeth
delayed
patient.
Several
Recalcification
except
of
for
removed
EHDP
bone
M
September
1953
2 years.
Lumps
on back
and
4
5
F
F
Initial diagnosis
ofsarcoma
from
2 years.
1954
Lump
on
of head
Several
Extensive
geal
back
phalan-,
deformity.
Mentally
Low
Low
clinical
progressive
Response
gery varied
Recalcification
delayed
Some
episodes
of
myositis
considered
to surwith Site
to be due to trauma
vit.
D diet.
-
EHDP
-
Main
foot
retarded
1 .1 years.
Stiff neck
improve-
in function
stiffness.
EHDP
neck
May
September
1951
Radiotherapy.
Steroids.
Useful
ment
feature
stiffness
3
disabled
vit.
Recalcification
One
D diet.
Possible
increase
mobility
EHDP
while
Gross
disability
to ossification
EHDP
in
on
due
near
left hip at age 20
6
M
2
October
1963
years.
Lump
Initial
on back
diagnosis
congenital
of neck
Prednisone.
hallux
valgus
Fixation
of left
hip joint.
Mineralisation
de-
-
Celltllose
phosphate.
Low calcium
feet in metaphyses,
possibly
due to
diet.
EHDP
EHDP
7
M
October
2 years.
1965
Initial
Lumpson
ulna,
limbs:
tibia,
humerus
8
F
July
2 years.
1947
Torticollis
diagnosis
congenital
Biopsy.
EHDP
hallux
valgus:
later,
physial
aclasia
Bilateral
valgus
dia-
Prednisone.
-
Calcification
hallux
operation
at
Progressive
rigidity
site of operation
on toes
Recalcification
Several
EHDP
TABLE
HISTOLOGY
AND
EFFECTS
OF OPERATION
II
IN FIVE
PATIENTS
EHDP
HAVING
EHDP
Date
number
Doseat
time
of operation
Case
started
I 3.3.70
(mg/kg)
20
40
Type
of operation
Removal
of ectopic
right calf
and
right
bone
21.4.70
I 7.6.70
elbow
Lamellar
and
no excess
partly
with
4.4.70
20
Removal
right
foot
20
Biopsy
muscle
of right
Removal
of
20
of
bar
of
bone
biceps
23.9.70
Inactive
27.4.71
Active
14.4.71
20
Removal
around
21.1.72
20
Removal
12.71
20
fibre
osteoid
No
clear
of
recurrence
evidence
Ectopic
hone;
bone:
lamellar
bone
excess
osteoid
seams
ectopic
bone
myositis.
bone
from
I I . 10.71
Compact
and
osteoclasts
of bone
right
8.9.71
thigh
of bone
quadriceps
6
osteoid.
mineralised
wide
with
no
Segmental
Removal
of
right
scapula
left
27.3.72
muscle
Ectopic
bone
osteoid
tip
bone
over
to
bone
Compact
blasts
cancellous
and
Skeletal
5
bone
disintegration
No evidence
recurrence
of
Recurrence
few
Recurrence
of
sarcoplasm
left hip
3
fibrous
of operation
Lamellar
bone with few osteoblasts,
no
osteoclasts,
no osteoid.
Post-mortem
(January
1971): Skeletal
bone:
porotic:
2
Effect
Histology
Date
bone
with
or osteoid
with increased
thickness
of
10 lamcllae;
few osteoblasts.
: excess osteoid
and
and
ectopic
no osteoblasts
trabecular
bone
with
No
evidence
of
recurrence
Recurrence
osteo-
osteoclasts
5.72
Recurrence
THE
JOURNAL
OF
BONE
AND
JOINT
SURGERY
MYOSITIS
Case
six
3-A
weeks
radiograph
after
resection
taken
in July
of
ectopic
removed
OSSI FICA NS PROGRESSI
1971 showing
bone
(arrowed)
in
ectopic
September
was
still
bone
51
VA
in front
of the right
1971.
The
sharp
edge
present
two years
later.
hip.
where
FIGs.
showing
blastic
FIG.
VOL.
58-B,
No.
I. FEBRUARY
9
976
Figure
that
7-A
bone
7 TO
has
been
9
preparatioll
showing
thick
in the bone resected
in September
1971 . (Undecalcified
Von
neutral
red, viewed
under polarised
light,
320.)
Figure
similar
preparation
of ectopic
bone,
again
demonstrating
osteoid.
Figure
9-A
histological
preparation
of ectopic
Case
3.
The appearance
even
activity.
histological
immature
(Decalcified,
;
hone
presents
haematoxylin
little evidence
and
eosin,
osteoid
Kossa,
8-A
thick
bone
of osteo170.)
52
R. SMITH,
R. G.
G.
RUSSELL
AND
C.
G.
WOODS
..
-
--
--4.
J.;i:
FIG.
Case
4.
Figure
10-The
10
right
hand.
Figure
1 1 -Radiograph
of the left hip which was fixing the joint (Fig. 3).
Because
the mass of ectopic
bone surrounded
the main neurovascular
bundle,
not all of it could be removed
(Fig. 4) and no increase
of movement
was produced.
The mixed compact
and can-
of the right
Case 4-This
to 12), partial
retardation.
hand
to show
the skeletal
abnormalities.
girl had severe
skeletal
abnormalities
alopecia,
webbing
of the neck
Chromosome
analysis
was normal.
(Figs.
10
and
mental
In 1969 she
cellous
ectopic
bone had a few areas ofosteoclastic
resorption;
no osteoblasts
or osteoid
were
seen.
Four
months
after
operation
there
was
no evidence
of recalcification,
but at
seven
months
recalcification
more dense (Fig.
especially
of the
5).
left
had
begun
Progressive
leg, now
and
gradually
became
limitation
of movement,
confines
this
patient
to
a
wheel-chair.
Case 3-In
this boy operations
to remove ectopic bone began
in
1963.
Short courses
of radiotherapy
were also given and
in 1969 he started
to take prednisone
7.5 milligrams
daily.
Bone was excised from the right hamstring
muscles in January
1970 and again in September
1970, with further
recurrence.
In
April 1971 EHDP
(20 milligrams
per kilogram
per day) was
started
and prednisone
discontinued.
In May 1971 bone was removed
from the biceps on both
sides,
which
gave increased
movement.
In September
1971 a
considerable
amount
of the bone which
had developed
around
the right
hip (Fig. 6) and in the right hamstring
muscles
was
removed,
with some
improvement
in function.
Radiographs
taken
in 1973 showed
continued
no evidence
of recurrence;
EHDP
was
same dose.
Histology
of the skeletal
bone removed
at the hip operation showed
that up to half the bone
surfaces
were covered
with osteoid,
varying
in thickness
from two to eleven
lamellae
(Fig.
7); osteoblasts
of active
appearance
were present
on a
small part of the osteoid
surface.
Ectopic
bone removed
from
the thigh showed
partly
lamellar
and partly
woven
bone, with
islands
of cartilage.
Osteoid
covered
nearly
all the surfaces
of this ectopic
bone
(Fig.
8); it was up to ten lamellae
thick
and
uncalcified
present
The
at the
only
presence
treatment.
woven
on
a small
of osteoid
osteoid
part
was present.
of the
was attributed
woven
Osteoblasts
surfaces
were
(Fig.
to the diphosphonate
9).
FIG.
Case
4.
ectopic
Radiograph
calcification
12
showing
extensive
over the left hip.
began a vitamin
D-free
diet and regular
physiotherapy;
EHDP
10 milligrams
per kilogram
(600
milligrams)
per day was
started
in 1970.
Six months
later
there
was said
to be an
increase
in mobility
but this was difficult
to confirm.
An active
THE
JOURNAL
OF
BONE
AND
JOINT
SURGERY
NIYOSITIS
OSSIFICANS
53
PROGRESSIVA
.
-:
‘e
_
.
(
#{149}.:-
:.
:‘*!t
:
.
.;
<
15
FIG.
Figure
13-A
radiograph
in October
1972 showing
further
Case
are
taken in May 1972 showing
where bone was removed
in March
calcification.
Figure
15-A
histological
preparation
ofthe ectopic
5.
numerous
active-looking
osteoblasts
related
(Undecalcified,
focus
of myositis
subsided
without
EHDP
was
had
any
appeared
evidence
reduced
improvement
to
in mobility
200
osteoid
plastic
in the left arm
of calcification.
milligrams
appeared
to
of
normal
embedded.
and partially
Subsequently
daily
to continue.
thickness
and
Toluidine
blue,
a radiograph
and
the
In July
1973
ofswelling
showed
multinucleate
Figure
removed
14-A
radiograph
in March
1972.
osteoclasts
in
arm,
which
had
four
months
the right
of
upper
due
to myositis
girl became
to fixation
This
but
left
this
was
of the
less
of
more
bone
bone,
partly
the trabecular
marked
at
and
were
tissue
and
five
by about
weeks
later
at the operation
months
(Fig.
14).
of compact
partly
woven.
osteoblasts
that
fibres
immature
were
areas
of
In
Some
seen
between
there
was a large
amount
bone
with
appositional
July
shoulder
developed
but
Because
of the
previous
dose
EHDP
was
of
twice
daily.
The
radiographs
and
the
October
Figure
16-A
of
the
same
radiograph
an episode
case
taken
tional
VOL.
58-B.
No.
I. FEBRUARY
of
of myositis.
in January
calcification.
1976
the
right
arm
Figure
17-A
1973 showing
increasing
taken
in
radioaddi-
bone
fibrous
tissue
numbers
of
ossification
active
and
stiffness
recurrence
to
right
surgery
800
gradually
the
calcification.
after
doubled
swelling
of
no
the
milligrams
resolved
(Figs.
mineralisation
but
16
but
patient
of absorption
supports
this
no
clear
increased,
with limited
the rapid
evidence
remineralisation
of
movement
myositis
or
The dose of EHDP
has varied from 800 to 1,200
daily,
and a diet low in vitamin
D was begun
in
1972.
Radiographs
taken
in February
1973 suggested
calcification
in the region
of the left hip.
In this
lack
of cartilaginous
showed
progressive
has slowly
mandible
milligrams
5.
and
trabeculae
17).
calcification.
1972 during
rapid
and
of
and
atrophic
and
and
radiographs
pain
surface
active
growth.
pain
temporarily
revealed
The disability
of
Case
July
graph
swelling,
there
site
trabecular
the
granulation
bone
1972
and
On the
looked
which
looked
like fracture
callus;
large
osteoblasts
were related
to intramembranous
to
30 degrees
Seven
osteoclasts.
muscle
15). In addition
(Fig.
knee
consisted
multinucleate
degenerating
left
mobile.
remineralisation
removed
lamellar
bone
occasional
17
the site
previously,
hip
became
evidence
The
FIG.
been
rapidly
left
flexion
hip
some
and
ofthe
improved
the
was
16
lacunae.
disabled
at the age of twenty
by ectopic
bone.
In 1972 EHDP
was
started
in a dose
of 800
milligrams
(20 milligrams
per
kilogram)
daily
and
after
two
months
ectopic
bone
was
removed
by Mr J. Cockin
from the left quadriceps
(Fig. 13).
due
FIG.
resorption
taken
There
170.)
>‘
and redness
no calcification.
Case 5-This
1972.
bone
local
may
be due
to
of EHDP.
The histology
of the removed
idea, showing
cellular
activity
without
the
54
R. SMITH,
1I’..
Case
6-Radiographs
bone
after
two
taken
years
patchy
of treatment
thick
level
osteoid
seen in Case
of plasma
phosphate
being
absorbed.
G.
RUSSELL
with
EHDP.
The
18--A
However,
suggests
again
in May
growth
knee.
plates
Figure
the moderately
that
some
EHDP
raised
was
boy was treated
wider
taken
in 1972
such
dense
as
Case
metaphyses
bone
pain
7-This
milligrams
to
or
boy
per
continued
plates
1974
and
dense
were
seen
show
the
development
metaphyses
(Fig.
18).
the wrists
and hands
(Figs.
19 and 20).
These
appearances
may be due to EHDP.
This boy has had no symptoms
of vitamin
D deficiency
rickets
Similar
growth
and
proximal
was
kilogram)
EHDP
daily
progress;
in
myopathy.
given
several
areas
milligrams
(20
his condition
400
1973
from
of
but
myositis
over
the
back
rapidly
calcified.
Swellings
on both sides of the neck simulated
mumps.
The neck and trunk
became
very stiff as the myositis
subsided
and calcification
appeared.
This rigidity
made
him
more
liable
to accidents;
on a day at the seaside
he fell into
a few
inches
of
water
and
Case
8-This
patient
has
is being
followed
elsewhere.
1971)
began
which
appeared
to
prednisone,
From
ectopic
to take
increased
to take
to
but
nearly
improve
steroids
drowned.
50 milligrams
mobility;
were
later
discontinued
in 1955,
daily
this
was
after
changed
two
years.
1960 to 1970 her condition
bone was removed
from
changed
little;
in 1968 some
the back.
In 1972 she began
EHDP
10 milligrams
per kilogram
daily;
this
was
to
20 milligrams
before
ectopic
bone
was twice
from near the scapula,
with temporary
improvement
removed
in movement
but eventual
are
recurrence
discussion.
the
natural
ossificans
history
and
progressiva
possible
merit
treatbrief
in appearance
metaphyses
are
metacarpo-phalangeal
Cause-This
and
been
Conkling
the skeletal
of ectopic
(Rosborough
(Malter
the situation.
be
(Letts
lesion
Eaton
proliferation
trophic
the
all the
tissue
doubt
to clarify
were
found
suggests
tissue
around
that
is
with
from
tissue
are
For
these
we have
of myositis
subsequent
dysSmith,
evidence
before
that
over-
secondary
reasons,
of
not
to connective
and
because
to use the established
progressiva.
phalangeal
They
muscle.
exaggerated
; in contrast,
continued
ossificans
the
The striking
appearance
Case 2 suggests
that
tissue.
to
that
the
there
ossification
biopsy
changes
in this
proliferation.
of
little
and Deiss (1966) provide
is intrinsically
abnormal
in the
diagnosis.
do
pathology
tissue
and
still exists,
term
the
The
of connective
muscle
relation
pseudohypopara-
in two patients
of connective
Zeman,
Johnston
the muscle
tissue
with
1972)
consider
calcification
growth
and
McAlister
1968).
(1957)
twins
The
is likewise
mysterious:
reports
with multiple
congenital
ab-
is in connective
a!
et
is undoubtedly
monozygotic
1957).
1966)
and
of
to be a
wrist.
disorder
in
ends
appears
20-A
Daeschner
Chromosomes
normal
primary
The
abnormalities
bone
formation
normalities
there
reported
and
thyroidism
and
Figure
obscure.
has
of the growing
dense,
joints.
is quite
inherited
abnormalities
are
present
at
are essential
birth
and
are
to
usually
followed
by acute
episodes
of myositis
and subsequent
extraskeletal
ossification.
The abnormal
big toes may be
dealt with surgically
as a form ofcongenital
hallux
valgus
without
recognition
of their possible
significance
(Case 7).
Erroneous
diagnoses
may be given for the myositis.
Pain,
redness,
and
infection
; myositis
mandible
of calcification.
DISCUSSION
diagnosis,
myositis
the change
widened,
lesions
The cause,
ment
of
WOODS
Diagnosis-The
been seen only once (by R. S.) and
The patient
(Case 2 of Illingworth
cortisone
G.
1974 showing
19-Four
from January
to June
1966 with
prednisone
20 milligrams
daily,
later reduced
to 5 milligrams
daily and continued
until 1971.
In 1972 he was also given
cellulose
phosphate
5 G thrice
daily and a low calcium
diet.
Since
October
1972,
and during
treatment
with
EHDP
250 milligrams
(10 milligrams
per kilogram)
daily,
occasional
transient
swellings
around
the
mandible
have
given
an
appearance
similar
to mumps.
Comparison
of radiographs
of
C.
(Eaton,
Case 6-This
of the knees
AND
FIG.20
1972 and
Figure
3.
G.
U
in October
decalcification.
R.
general
may
be
may
possible
relation
sarcoma
may
the
most
may
disturbances
the
simulate
mumps
mistaken
for
to
(Case
marked
aspect
be prolonged
3).
JOURNAL
and
(Cases
and
When
of the
(Case
may
neck
bruises,
(Case
trauma
be suggested
histology
THE
systemic
around
of
6 and
7);
which
2);
the
the
soft-tissue
confirmed
progressive
rigidity
delay
by
is the
in diagnosis
2).
OF
BONE
AND
JOINT
the
the
stresses
and
apparently
disorder
suggest
angle
SURGERY
MYOSITIS
Natural
history-We
the
of
acute
muscles.
ectopic
bone
this
often
answers
will
agents
may
phates
or
lesion
help,
for
The
late
adolescence
(Case
that
years
the
crippling
ossification
childhood
common
or early
in smaller
must
also
(1964)
around
are
For
instance
fixed
improve
the
by extensive
the
movement
may
by
mobility
the
patient,
as in Case
in Case
that
of
in late
spontaneous
seem
first
radiographs,
the only practical
usually
taken
strong
a sudden
vigorous
less
rapid
ectopic
the
and
less
bone
limited
in
myositis
of
ectopic
certain
rather
data
which
way of detecting
infrequently.
are
after
than
available
ossificans
of
forced
increase
in
bone
of old
formed
one
matrix
have
been
may
still
both
and
its
conclude
the
that
mineralisation
Treatment
aims
ectopic
of treatment
immobility,
causing
and
crippled.
Because
treatment
discussed
VOL.
No.
to
are
to prevent
fixation
of
increase
of our
mobility
ignorance
by Mair
I. FEBRUARY
the
joints
(1932)
1976
in
of
calcium
malacia,
although
The
EHDP
attempts
by Lutwak
(1964)
at
A low
the
striking
bone.
6, has
not
significantly
vitamin
D diet
possible
(disodium
tion
elsewhere
and
turnover
The
that
they
on bone
cells,
either
activity.
Thus
activity
is a consistent
patients
with
Smith,
used
disease
fifty-two
be delayed,
been
bone
patients
et
a!.
Our
1972)
if not
mixed
feature
with
after
been
in Case
that
Our
3 there
known,
reducing
of the
EHDP
1974).
EHDP
bone
of
(Russell,
has
of active
been
myositis
I 97 1 ; Schnakenburg
surgical
removal
reviewed
experience
suggested
Richelle
osteoblastic
et a!. 1972).
(Russell
prevented.
; thus
et a!.
Bisaz,
resorp-
important
of
of areas
has
(1973).
is not
or indirectly
treated
mineralisation
ectopic
and
action
additional
Walton
and Woods
ossificans
progressiva
to prevent
of
animals
Fleisch
suppression
histological
Paget’s
Preston,
myositis
have
directly
early
dissolution
(Fleisch,
Russell,
excessive
bone
oftheir
been
Such
experimental
Morgan,
may
have
1973).
and
and
diets
children
is the phosphonate
Smith
in
no
osteo-
calcium
properties
formation
mechanism
it is possible
series
and
(Gasser,
exact
been
of
of low
whose
the
has
in growing
in this
(Russell
prevent
and
1972).
there
We have
ectopic
evidence
effects
etidronate),
bone.
delayed
that
mineralisation
apatite
crystals
in vitro,
and
prevent
both ectopic
calcification
M #{252}hlbauerand Williams
1970)
has
ectopic
to differ
histological
not be disregarded.
main agent used
(Russell
already
of
be
bone.
has been
restriction
as in Case
also in skeletal
measures
have
or
skeletal
compounds
in
bone
may
agent
EDTA
that dietary
diet.
It is also
biochemical
Whiteside
progressive
patients
the many
and
formation
and
or ectopic
as by mineralised
it is unlikely
presumably
that
these
established
bone
58-B,
of a low
primarily
ofjoints
mineralisation
but
improve-
would
tissue
mobility
phosphate,
(Bassett
et a!. I 969 ; Weiss
et al. 1972) or remineralisation
inevitable.
The
fibrous
the
partial
of sunlight
is a different
approach
and
an attempt
to produce
osteomalacia
in ectopic
In
are
reduce
mineralisation.
reformation
might
mineralisation,
they
by unmineralised
clinical,
their
From
although
restriction
effects
“inactive”
bone.
sup-
they
prevent
produce
that
terms
assessed,
that
bone,
fibroblasts
to
unlikely
of cellulose
reviewed
physiotherapy
hitherto
removal
progressiva
from
should
early remineralisation,
Recurrence
is probably
newly
fully
may
4.
because
been
bone.
episode
on
only
of either
can
effect
in retarding
Surgical
removal
of ectopic
bone
is thought
to be
followed
inevitably
by rapid
recalcification
at that site.
The speed
with
which
this occurs
is not clearly
documented,
calcium
The
when
of an elbow
follow
with
as limited
represents
would
is
formation
bone,
and
no evidence
occur
it
prolonged
it. Dixon,
Mulligan,
Nassim
and
that ACTH
and cortisone
failed
could
In practical
neck
the
2, or possibly
the
and
by ectopic
of extraskeletal
to
affect
most
fiexion
appear
because
the
this
following
ment
that
myositis,
noted
of acute
ofectopic
effects
measures
effective,
the
possibility
fixed
Theoretically,
around
may
known
to suppress
(1954)
found
reossification.
however
of
in
out
their
be expected
Stevenson
to prevent
6), whereas
hip
bridges
that
years
This
myositis.
the
unlikely
it seems
in
pointed
occur
More-
varies
affected
the formation
prevent
of
outstandingly
in one of two patients
treated
is no clear evidence
that these
Early use of the calcium
chelating
ineffective,
and there is no evidence
adult
life (Case
5). Ossification
is unmuscles
and in those of the abdomen.
however
joints
has
apparently
myositis
There
of
tendency
bone
variably
often
7).
the
found
(1971)
just
quies-
6 and
(1957)
in
occur
rate
been
et a!.
effects
can
matrix.
that
the
2 that
I , 3 and
(Cases
consider
improvement,
Case
are
in child-
can
ectopic
lesions
back
active
(Cases
from
body
Early
over
that
of comparative
remineralise
of the
ossification.
acute
demonstrate
in children
variable
Lutwak
parts
the
unlikely
ossification
even
be very
sites.
different
as
many
and
to
patients
by
after
or
different
One
our
is a suggestion
mineralise
of
to be more
but
followed
may
there
pathology
having
corticosteroids.
because
lRF,9mTcpolyphos
it is very
is thought
life,
5),
progression
scanning
none
Eaton
systemic
of active
agents
is a possibility.
myositis
cence
these
empirical,
However,
reduced
the
Illingworth
pression
with
few,
bone
largely
successful.
cortisone
and
how
spon-
mineralisation
but
‘7Sr,
the
known
subside
55
PROGRESSIVA
remain
could
occur,
but healing
of milder
without
marked
local
symptoms
or
in adult
crippling
outcome
relatively
obtain,
If
condition
than
over
to
example,
disturbance
hood
and
easy
not
show
are
2 is characteristic,
healing
myositis
systemic
to
be
is
lesions
only
findings
ft9mTc..EHDP.
complete
recurrent
the
radiographs
not
Case
in
it
often
pathological
normal
and swelling
within
the
that
in some
episodes
follows,
or how
Because
because
of the
of pain
it is clear
formation
occurs
taneously.
and
are ignorant
episodes
Although
OSSIFICANS
by
with
Cases
mineralisation
subsequent
was
good
of
The
effect
Geho
and
I and
could
experience
radiological
2
56
R. SMITH,
evidence
ofdelayed
tions in Cases
fication
despite
that
EHDP
disorder
The
other
mineralisation
slowed
in children
response
agent,
may
of
natural
influenced
which
RUSSELL
has
continued
active
has
any
of
the
activity
the
disease,
EHDP
side
in
plasma
tissues
still
and
high
of
although
improve
mobility
of
Geho
might
and
by this.
calcification
(THP)
excretion,
be due
to age.
biceps
which
subsequently
All the patients
during
persons
lesion was
an episode
that
in myositis
than
normal,
were
on high
and
related
measured
after
indicator
to it.
excreted
of measurements.
in Case
5 may
to the
EHDP
is in any
values
obtained
failure.
have
been
in brackets
high
way
An
and
were
in Paget’s
disease
to the following
who kindly
referred
patients
he
inhibition
had
with
the
(Russell
conversion
et a!. 1974).
Therapeutic
progress
while
the
advantage
in these
young
to us: Professor
Weiss,
decreased
bone
their
patient.
rapidly
6)
which
point
to a
though
significantly
as muscle
weakness
abnormal
his
dietary
For
various
skeletal
to treatment
intake
of calcium
reasons
it seems
is a direct
than
effect
metabolites
in this
disorder
is likely
cause
remains
unknown,
of a relatively
patients
can
of
due to interference
D to its active
underlying
C. E. Dent
of the
skeleton.
be attributable
of vitamin
in
O’Connor
detected
in the
youngpatients(Case
rather
23
values
turnover
in
of mineralisation
tissues
to
THP
aspect
the
The
may
time.
small
increase
be considerable.
to be
but
in mobility
(Cases
2, 4 and 6), Mr J. A. Mantle (Case
Professor
R. Kilpatrick
(Case 8).
5), Mr T. A. English
(Case
7) and
and R. G. G. R. from the National
(Case
Trust,
on
may
signifi-
1971
important
absent.
boy
also
a long
the
to be dose-
the
measurement
were
on calcifying
slow
April
collagen
be most easily
and in one ofour
but
for
EHDP
in plasma
C. M. Squire
(Case
I), Mr T. C. Howard
Davies
R. S. is in receipt
of a grant
from
the Weilcome
EHDP
this
in
from
fall
Kirschbaum,
effect
is no
changes
THP
increased
Bland,
Another
in this
There
the
day
impressed
hydroxyproline
(I 97 1 ) demonstrated
pain,
restricted
that
by
this.
observed
changes
in the metaphyses
normal
mineralisation,
of classical
rickets,
such
bone
with
absorption
appears
of the
may
mineralisation
he was developing
increase
were
of
signs
per
ir-
et al. 1971;
been
total
3 did
may
hyperphospha-
show
Further,
radioisotope
effects
not
on
effects.
EHDP
(Weiss
of the
in the
progressiva
produces
Case
1972.
Phang
by
there
failure
other
some
is its possible
and
the
ectopic
possible
that
we have
milligrams
growingpatient,
absorption
possible
the
and
(1973).
EHDP
Fisher
the number
that
low-a
Similarly
at the time
mineralisation.
which
We are indebted
the figure
These
values
suggest
have
been
particularly
deficient
phosphate,
and
effects
recurrent
other
EHDP
In only
Wharton
of
Such
1973),
suggested
turnover
1974; and Case 7, 0-77 per cent, the
being the percentage
of the daily dose
therapeutic
6 may
of
use
It is
on
disorder
and
is less
the
ectopic
interested
prevent
calcification
effect
evidence
is no
this
on
patients
there
Case 2, 1-27 per cent (three);
Case 5, 0-33 per
Case 6, 0-75 per cent in May
1973 and 8-25
in the urine
in Case
then
the
usual
3 showed
ossificans
present
93
before,
negligible.
is by
of
of treatment
suggested
a consistent
in March
how
much
EI-LDP
has
excretion
is probably
only
if the urinary
excretion
months
dose,
even
our
milligrams
in normal
between
absorption
patients
However,
several
per cent in February
values
in each case
Mr
of EHDP
progressiva
in some
of the
as follows:
cent (four);
signs
doses
and
in Case
myositis
that
cantly-from
of the administered
dose,
and that it
if taken
when
fasting.
It is possible
ossificans
indirectly
thigh
mineralised.
at present
difficult
to measure
been absorbed
because
urinary
clue
the
still active ; indeed
at the
of myositis
in the right
and after operation.
It is known
that
the absorption
is both low and variable,
I and 10 per cent
is probably
highest
an
around
the
particularly
to
been
Whiteside
that
this
was
of
mentioning
in
It is known
of
prevent
been
its effect
evidence
to
of EHDP
examination
characteristic
EHDP
it has
taemia
be because
time there
EHDP
EHDP.
of
erroneously
led us to think that
result in the thigh.
It is possible
failure
much
that
none
removed
it is worth
ossification,
of remineralisa-
bone
we have
tion in the foot may have
we could achieve
the same
could
same
effect
Thus
5 showed
that
of osteoid
ability
Thus,
and
tissues
skeletal
doses
possible
phosphate
different
Case
and
thickness
respective
prevention
from
active
Although
dose
effect,
of how
way of assessing
the
of its effect on tissues.
was
with
because
in a daily
without
indicator
on bone could
be demonstrated
; in retrospect,
remineralisation
was not therefore
unexpected.
By contrast,
both
on the amount
of the
be a further
absorbed.
excised
bone
excessive
kilogram
the apparent
may
ectopic
stage
WOODS
Another
examination
of the
7).
or to
G.
been
will depend
to take
per
be a factor;
the
C.
related,
opera-
progress
AND
between
tissues in different
the amount
reaching
the
there
was
a moderate
increase
suggesting
good absorption.
In Case 2 variation
between
also
G.
dosage
and on intestinal
absorption.
of EHDP
treatment
in Case 7 might
very
milligrams
by
in turn
to the
patient
20
the
variations
and
by
duration
oforal
Thus the failure
this
down
be
site,
be related
subsequent
with active
myositis
(Case
of the patient
to EHDP,
disorder,
by possible
parts
of the body,
and
(i.
2, 5 and 8 have been followed
by recalcihigh doses,
and there
is little evidence
has
mineralising
; but
R.
Fund
for
Research
in Crippling
Diseases.
treatment
of myositis
3),
REFERENCES
Bassett,
C. A. L., Donath,
A., Macagno,
ossificans.
Lance!,
2. 845.
Bland,
J.
I-I.,
Kirschbaum,
parathyroid
Dixon,
T.
36-B,
F.,
extract
Mulligan,
B.,
O’Connor,
on urinary
L.,
F.,
Nassim.
Preisig,
G.
excretion
R.,
and
T.,
R.,
and
Fleisch,
Wharton,
of connective
Stevenson,
H.,
E.
tissue
F.
H.
and
Francis,
M.
D. (1969)
Diphosphonates
in the
(1973) Myositis
ossificans
progressiva.
Effect of intravenously
components.
Archives
of Internal
Medicine,
132, 209-212.
( I 954)
Myositis
ossificans
progressiva.
Journal
of
Bone
and
Joint
given
Surgery,
445-449.
THE
JOURNAL
OF
BONE
AND
JOINT
SURGERY
MYOSITIS
Eaton,
W.
L.,
Conkling,
W.
S.,
and
Daeschner,
C. W.
OSSIFICANS
(1957)
Early
myositis
ossificans
clinical
and pathologic
study.
Journal
ofPediatrics,
50, 591-598.
Fleisch,
H. A., Russell,
R. G. G., Bisaz, S., Mlihlbauer,
R. C., and Williams,
formation
ofcalcium
phosphate
crystals
in vitro and on aortic and kidney
I, 12-18.
Francis,
M. D., Russell,
R. G. G., and Fleisch,
H. (1969) Diphosphonates
pathological
calcification
in rho.
Science,
165, 1264-1266.
Gasser,
A. B., Morgan,
D. B., Fleisch,
H. A., and Richelle,
Clinical
Science,
43, 31-45.
Geho,
W. B., and Whiteside,
J. A. (1973)
Experience
with
Metabolic
Bone Disease.
Proceedings
ofan
international
L. J. (1972)
57
PROGRESSIVA
D.
A.
progressiva
(1970)
calcification
The
The
formation
influence
of two
in
homozygotic
inhibitory
effect
of
EuropeanfouurnalofClinical
in vivo.
inhibit
occurring
of calcium
A
phosphonates
on
Investigation,
phosphate
diphosphonates
twins.
crystals
on calcium
the
in vitro
and
metabolism
n
the
Aspects
of
rat.
Detroit,
June
Congress
lllingworth,
26-29
Series
1972, pp. 506-51
by B. Frame,
A. M. Parfittand
of ectopic
ofmetabolic
H. Duncan.
In Clinical
calcification.
hone disease,
Amsterdam:
Henry
Medica,
Excerpta
Ford
Hospital,
International
No. 270.
R. S. (1971)
corticosteroids
Letts,
R. M. ( 1968)
1. Edited
disodium
etidronate
in diseases
symposium
n clinical
aspects
Myositis
ossifIcans
and observed
for
Myositis
ossificans
progressiva
I 6 years.
progressiva
(Munchmeyer’s
Archives
of Disease
: A report
of two
disease).
Brief
review
with
Childhood,
46, 264-268.
cases with chromosome
studies.
report
of two
cases
treated
with
in
Canadian
Medical
Association
Journal,
99, 856-862.
Lutwak,
L. ( I 964) Myositis
ossificans
of Medicine,
37, 269-293.
McKusick, V. A. (1972) Heritable
Mair,
W.
F. (1932)
Myositis
progressiva.
Disorders
ossificans
Mineral,
ofC’onnectiie
progressiva.
metabolic
Tissue.
Edinburgh
and
Fourth
Medical
1. ‘I., and McAlister,
W. H. (1972)
Pseudohypoparathyroidism
of the Canadia,z
Association
of Radiologists,
23, 27-32.
Paterson,
C. R., Woods,
C. G., and Morgan,
D. B. (1968) Osteoid
radioactive
Malter,
studies
edition.
and
St Louis:
N.S.
Journal,
39,
myositis
in metabolic
of the
13-36,
ossificans
bone
disease.
effects
of hormones.
C. V. Mosby
A,nerican
Jouiruzal
patient.
Jouruzal
Company.
69-92.
progressiva
Journal
in the
same
of Pathology
and
Bacteriolog;,
95,
449-456.
Rosborough,
D.
(1966)
Ectopic
bone
formation
associated
with
multiple
congenital
anomalies.
Journal
of
Bone
and
Joint
Suugerv.
48-B,
499-503.
R. (1973)
Diphosphonates.
Journal
of Bone
and Joiizt
Suurgerv,
55-B
66-86.
R., Bishop,
M. C., Price,
D. A., and Squire,
C. M. (1972)
Treatment
of myositis
diphosphonate.
Lance,’,
1, 10-12.
Russell,
R. G. G., Smith, R., Preston,
S., Walton,
R. J., and Woods,
C C. (1974)
Diphosphonates
in Paget’s
Schnakenburg,
K. V., Gross-Selbeck,
G., and Wiedemann,
H.-R.
(1972) Zur Behandlung
der Fibrodysplasia
‘Diphosphonat”
(EHDP).
Deutsche
nzedizinische
Wochenschrift,
97, 1873-1876.
Smith,
D. M., Zeman,
W., Johnston,
C. C., Jun.,
and Deiss, W. P., Jun. (1966)
Myositis
ossificans
progressiva.
Russell,
R. G. C.,
Russell,
R. 6.
Weiss,
I. W.,
Internal
VOL.
58-B,
and
G.,
Fisher,
Medicine,
No.
Smith,
Smith,
L.,
and
74,
I. FEBRUARY
Phang,
933-936.
1976
J.
M.
(1971)
Diphosphonate
therapy
in a patient
with
myositis
ossificans
disease.
ossilIcans
progressiva
with
a
I, 894-898.
progressiva
mit
Lauzcet,
ossificans
Metabolism,
progressiva.
15,
52 1-528.
Annals
of