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CHAPTER
37
Muscle, Tendon and Ligament in
Ost
eogenesis Imperfe
cta
Varun Puvanesarajah and Paul D. Sponseller
Bloomberg Children's Center, Baltimore, MD, USA
INTRODUCTION
revealed swollen mitochondria on electron microscopy
and elevated acid phosphatase activity. Although no
collagen mutations were found, gel electrophoresis of
lysed fibroblasts from the muscle biopsy demonstrated
extra protein that seemed to suggest hyperglycosylation
of the collagen I(α1) chain.
1
Muscular collagen content
has also been assessed in several other OI cases. In par-
ticular, diminished collagen content has been observed
in the uterine myometrium of a pregnant OI patient.
2
This has been hypothesized to contribute to previously
reported uterine rupture in female OI patients.
3,4
Other
histological changes have been reported in the myocar-
dium of OI patients. In one patient, significant intersti-
tial fibrosis and hypertrophy were observed.
5
Skeletal muscle pathology has been investigated in
mouse models of OI.
Oim
/
oim
mice exhibit the synthe-
sis of type I collagen (α1) homotrimer due to a mutation
affecting the COL1(α2) chain, which, though relatively
rare, has been observed in patients.
6,7
Interestingly, a
recent study demonstrated that muscles present in the
hindlimbs of
oim
/
oim
mice had less fibrillar collagen
and were generally smaller. Although
oim
/
oim
mice
were generally smaller than wild-type mice and thus
would be expected to have decreased muscle mass,
whole muscle wet weights were less than expected
when normalizing for size. Additionally,
oim
/
oim
mice
generated lower peak tetanic forces and were unable
to sustain forces for extended periods of time, when
normalizing for fibrillar cross-sectional area, suggest-
ing reduced overall contractility. Despite these changes,
there were no significant differences in muscle fiber
type composition between wild-type and
oim
/
oim
mice and cross-sectional area of muscle fibers was not
decreased in
oim
/
oim
mice relative to wild-type mice.
8
There have also been numerous clinical studies
that have demonstrated decreased muscle strength
The effects of osteogenesis imperfecta (OI) on bone
are well documented and clinically apparent as chil-
dren and adults with this condition experience multiple
fractures throughout life. However, there is a dearth of
information pertaining to the effects of OI on muscles
and tendons. Injuries to muscle and tendons occur fre-
quently, but are usually unreported by the patients
unless severe. Since the primary etiology of OI is due
to heritable mutations in normal collagen synthesis and
since both muscle and tendon have significant collagen
content, it is expected that OI would result in distinct
pathological consequences in muscle, tendons and liga-
ments. This chapter will review current knowledge con-
cerning these tissues.
MUSCLE
In clinical practice, frequent, early bone fractures are
often the presenting symptom that raises suspicion of
OI. However, there has been at least one reported case
of an OI patient who initially presented with significant
lower limb muscle weakness. In this case, a 2-year-old
boy experienced normal development, began walk-
ing at the age of 14 months, but had a positive Gower's
sign at presentation. X-rays showed generalized osteo-
penia throughout the skeleton and 18 months after
presentation, OI type IV was suggested after the occur-
rence of multiple vertebral fractures and low bone min-
eral density was found.
1
Similar scenarios are likely to
exist in other families of children with mild OI.
Lower limb examination included a computed
tomography (CT) scan, which revealed muscle atro-
phy and hypointense regions of fat. A muscle biopsy
