Minggu, 26 Oktober 2008

Scheuermann’s Kyphosis in Adolescents and Adults:

Scheuermann’s Kyphosis in Adolescents and Adults

Dr Harry Sunaryo SpOT

In 1920, Scheuermann first described
the entity of structural thoracic
kyphosis that now bears his
name. The clinical condition of
ScheuermannÕs kyphosis has widely
variable presentations that do not
necessarily correlate with the radiographic
findings; evaluation of a
lateral thoracic radiograph is necessary
to establish the diagnosis.
S¿rensen1 defined the radiographic
diagnosis of ScheuermannÕs kyphosis
on the basis of anterior wedging
of 5 degrees or more of at least
three adjacent vertebral bodies.
(This definition is helpful in differentiating
ScheuermannÕs kyphosis
from familial round-back deformity.)
Adolescents with Scheuermann
Õs kyphosis typically present
to medical attention on the urging
of family or teachers who are concerned
about the cosmetic deformity.
Adults who have been living
with the cosmetic deformity for
long periods of time usually seek
medical attention because of increased
pain. Although Scheuermann
Õs kyphosis has been well
described in terms of clinical presentation
and radiographic findings,
the etiology remains largely
unknown, and the indications for
treatment continue to be debated.
Normal Thoracic Kyphosis
Unlike scoliosis, in which any lateral
deviation of the spine in the
coronal plane can be deemed
abnormal, the sagittal alignment of
the thoracic spine displays a range
of normal that is dynamic. Thoracic
kyphosis typically increases
throughout life. Fon et al2 determined
that kyphosis in children
under the age of 10 years averages
20.88 degrees (SD, 7.85) for boys
and 23.87 degrees (SD, 6.67) for
girls; in adolescents up to age 19,
kyphosis averages 25.11 degrees
(SD, 8.16) in boys and 26.00 degrees
(SD, 7.43) in girls. The slightly
greater kyphotic deviation in females
increases after age 40. In
women aged 50 through 59, mean
kyphosis measures 40.71 degrees
(SD, 9.88); in age-matched men, it
is 33.00 degrees (SD, 6.46). While
the values are still debated, the
Scoliosis Research Society has stated
that the accepted range

ScheuermannÕs thoracic kyphosis is a structural deformity classically characterized
by anterior wedging of 5 degrees or more of three adjacent thoracic vertebral
bodies. Secondary radiographic findings of SchmorlÕs nodes, endplate narrowing,
and irregular endplates confirm the diagnosis. The etiology remains
unclear. Adolescents typically present to medical attention because of cosmetic
deformity; adults more commonly present because of increased pain. The indications
for treatment are similar to those for other spinal deformities, namely,
progression of the deformity, pain, neurologic compromise, and cosmesis. The
adolescent with pain associated with ScheuermannÕs kyphosis usually responds
to physical therapy and a short course of anti-inflammatory medications.
Bracing has been shown to be effective in controlling a progressive curve in the
adolescent patient. For the adult who presents with pain, the early mainstays of
treatment are physical therapy, anti-inflammatory medications, and behavioral
modification. In patients, either adolescent or adult, with a progressive deformity,
refractory pain, or neurologic deficit, surgical correction of the deformity
may be indicated. Surgical correction should not exceed 50% of the initial
deformity. Distally, instrumentation should be extended beyond the end vertebral
body to the first lordotic disk to prevent the development of distal junctional
mal thoracic kyphosis for a growing
adolescent is between 20 and 40
degrees, and that any degree of
kyphosis at the thoracolumbar or
lumbar area of the spine should be
considered abnormal.3
Epidemiology and
Pathogenesis of
Scheuermann’s Kyphosis
In 1964, S¿rensen1 reported a
prevalence of ScheuermannÕs
kyphosis of 0.4% to 8.3%. Of the
five studies that S¿rensen cited,
those by Wassman in 1951 and
Bonne in 1955 reported a prevalence
of 0.4%. While these represented
the larger series, they perhaps
contained inherent bias in
that they included only men who
had been rejected for military service
because of their deformity.
Realizing this potential bias, both
investigators estimated that the
total prevalence of ScheuermannÕs
kyphosis was between 4% and 8%,
which is more in line with the findings
of other investigators. In a
subsequent review of 1,384 cadaveric
specimens, Scoles et al4 reported
a prevalence of 7.4%.
It is generally considered that
the prevalence of ScheuermannÕs
kyphosis is approximately equal in
males and females. In S¿rensen’s
review,1 58% of the patients were
male, and 42% were female. There
are, however, widely divergent
reports on relative prevalence
between the sexes. Bradford3
reported a female-male ratio of 2:1
for the prevalence of Scheuermann
Õs kyphosis, while Murray et
al5 reported a 2.1-times higher
prevalence in males.
The age of onset of Scheuermann
Õs kyphosis is difficult to
establish. S¿rensen1 described a
ScheuermannÕs prodrome in patients
who have a Òlax, asthenic
posture from the age of approximately
4 to 8 years, and [in whom]
within a few years a real fixed
kyphosis has developed.Ó Radiographic
findings consistent with
ScheuermannÕs kyphosis are not
visible until the age of 12 to 13, corresponding
with the onset of
puberty. Therefore, adolescent
girls typically evidence the radiographic
findings before adolescent
The pathogenesis of Scheuermann
Õs kyphosis has yet to be elucidated,
although many theories
have been proposed. Scheuermann
Õs initial description included
a hypothesis that avascular necrosis
of the ring apophysis leads to
premature cessation of growth
anteriorly, which results in wedging
of the vertebral body. Schmorl
postulated that herniations of disk
material through the vertebral endplates
(which now bear his name)
lead to a loss of disk height and
anterior wedging of the vertebral
body.6 Subsequent studies disproved
these early theories, but
have not yet established a cause.
An underlying genetic factor has
been suggested. Halal et al7 reported
in 1978 on five families who
demonstrated an autosomal dominant
mode of inheritance with high
penetrance but variable expression.
Skogland et al8 reported on 62 girls
aged 9 to 18 years whose mean
height was 2.5 SDs above average;
18 had thoracic kyphosis greater
than 40 degrees, and 11 had additional
vertebral abnormalities consistent
with ScheuermannÕs disease.
Ascani et al supported a similar
correlation of ScheuermannÕs kyphosis
with height and also demonstrated
increased levels of growth
Although the anatomic and histologic
findings in Scheuermann’s
kyphosis are well established, the
cause-and-effect relationships are
less clear. Gross anatomic findings,
such as a thickened anterior longitudinal
ligament, narrowed vertebral
disks, and wedged vertebral
bodies, are consistent findings.2,9
Histologic abnormalities of the cartilaginous
endplate have also been
described. The ratio of collagen to
proteoglycan in the matrix of the
endplate is below normal in
patients with ScheuermannÕs
kyphosis. The relative decrease in
collagen is postulated to result in
an alteration in the ossification of
the endplate and thus altered vertical
growth of the vertebral body.6
It has also been postulated that
osteoporosis may be an etiologic
factor in the development of
ScheuermannÕs kyphosis. Bradford
et al10 prospectively studied 12
patients with ScheuermannÕs
kyphosis with an extensive osteoporosis
workup and iliac crest
biopsy. While their study did not
demonstrate cause and effect, it did
show that some patients with
ScheuermannÕs kyphosis have a
mild form of osteoporosis, and
dietary analysis demonstrated
some deficiency in calcium intake.
It was hypothesized by the investigators
that the osteoporosis may be
transient, presenting early in the
course of the disease before it
becomes radiographically evident.
Gilsanz et al11 subsequently reported
on 20 adolescent patients with
ScheuermannÕs kyphosis aged 12 to
18. No evidence of osteoporosis
could be demonstrated when compared
with controls as measured
by quantitative computed tomography.
However, this does not necessarily
contradict the theory that
early osteoporosis may be an etiologic
Mechanical factors have also
been postulated in the development
of ScheuermannÕs kyphosis.
Scheuermann initially noted a high
incidence of kyphosis in industrial
workers. The role of mechanical
factors is also supported in part by
the success of bracing.12 What
remains unclear in the mechanical
theory is whether the histologic
endplate changes predispose to the
development of pathologic kyphosis
or are secondary.
The indications for the treatment of
patients with ScheuermannÕs kyphosis
can be grouped in five general
categories: pain, progression of
deformity, neurologic compromise,
cardiopulmonary compromise, and
For appropriate evaluation, a
detailed history and physical examination
must be combined with
radiographic evaluation to document
the patientÕs status in each
History and Physical
The adolescent typically comes
to medical attention for different
reasons than the adult. Adolescents
often present on the urging of
parents, teachers, or friends, primarily
for cosmetic or postural
complaints. Pain is more commonly
the chief complaint of adults.
The issues in the history and physical
examination, however, are similar
for both groups.
If pain exists, its location, exacerbating
features, and severity
should be documented. Typically,
pain is located just distal to the
apex of the deformity in a paraspinal
location. If the pain pattern
is atypical, particularly in an adolescent,
other causes for the pain
must be ruled out. In the adolescent,
when pain or discomfort is reported,
it is most often activityrelated
and presents as either pain
in the typical area associated with
ScheuermannÕs kyphosis or simply
early fatigue. The symptoms are
most commonly relieved immediately
with rest and usually are not
activity-limiting. In adults, pain is
a much more common presenting
complaint. Hyperlordosis distal to
the thoracic deformity and subsequent
degenerative disk and facet
arthropathy predispose adults to
low back pain; the typical pain
over the deformity may coexist or
predominate. S¿rensen1 reported
that pain was the presenting complaint
in over 50% of the 103 patients
in his initial review. Other
authors have noted the occurrence
of pain in 20% to 60% of their
ScheuermannÕs disease may also
exist in a variant form (pseudo-
ScheuermannÕs disease), in which
the predominant deformity is at the
thoracolumbar or even the lumbar
region of the spine. Pain is typically
concordant with these variant
locations, and the cosmetic deformities
at these alternate locations
may not be as severe.13
Progression of the deformity is
an additional indication for treatment
of patients with Scheuermann
Õs kyphosis. Careful attention
to the history of the curve is essential.
The deformity may have been
ignored or considered to merely
represent poor posture; this combined
with typical adolescent hesitancy
and self-consciousness may
result in a delay in diagnosis. The
patientÕs perception that the deformity
is increasing and previous
radiographic evaluation can provide
concrete evidence of progression
of the deformity. Similar
issues should be addressed in the
adult, in whom radiographic confirmation
can more often be obtained.
Cord compression secondary to
ScheuermannÕs kyphosis is rare,
but when present may mandate
surgical treatment. The history of
onset of the neurologic compromise
is quite variable, ranging from
acute onset of unilateral radiculopathy
to insidious onset of spastic
paraplegia. The underlying
cause is that the spinal cord is
draped over the apex of the deformity.
A short-segment severe
deformity is generally considered
to be at highest risk, but this is not
fully supported in the literature.
Lonstein et al14 demonstrated an
average kyphosis of 95 degrees in a
mixed population of patients with
neurologic compromise, while
Ryan and Taylor15 showed an average
kyphosis of only 54 degrees in
three patients with ScheuermannÕs
kyphosis. Patients with Scheuermann
Õs kyphosis may also present
with extradural cysts or acute thoracic
disk herniations, which may
be exacerbated by the underlying
deformity and may cause neurologic
Cardiopulmonary complaints are
extremely rare on initial presentation
of patients with ScheuermannÕs
kyphosis. S¿rensen1 reported that
chest wall abnormalities had no
negative effect on cardiopulmonary
function. However, Murray et al5
documented restrictive pulmonary
disease in patients with kyphosis
measuring greater than 100 degrees,
with the apex of the curve in the
upper thoracic region.
Cosmetic issues related to the
curve should also be addressed
with the patient. These concerns
should not be underestimated as
the driving force that initially
brings the patient to medical attention.
However, when cosmesis is
an isolated indication for treatment,
particularly surgical intervention,
caution should be exercised.
The physical examination is
important in documenting the findings
of ScheuermannÕs kyphosis
(Fig. 1). Even in adolescents, the
sagittal deformity is fairly rigid on
hyperextension, whereas in the
patient with postural kyphosis, the
deformity is more correctable. Both
types of deformity may be rigid in
Clifford B. Tribus, MD
Vol 6, No 1, January/February 1998 39
the adult. Having the patient bend
forward and viewing the deformity
from the side is the best way to
delineate the kyphosis. Typically,
the cervical spine and the lumbar
spine display increased lordosis,
while the overall sagittal and coronal
balance is well maintained. The
shoulder girdles are often rotated
anteriorly; the combination of this
characteristic with the cervical lordosis
can produce a stooped and
awkward appearance. The arms
and legs will appear relatively long
compared with the shortened
trunk. The lower extremity should
also be evaluated, particularly for
hamstring tightness and underlying
neurologic compromise. On forward
bending, the patient with
ScheuermannÕs kyphosis will have
an ÒA-frameÓ deformity with a
more limited area of involvement
than the patient with familial
round-back deformity.
Radiologic Evaluation
Routine radiographic studies
obtained for evaluation of the patient
with ScheuermannÕs kyphosis
should include anteroposterior and
lateral radiographs of the entire
spine on long films and a hyperextension
lateral image of the thoracic
spine. The lateral radiograph
should be obtained with the patient
standing with knees and hips fully
extended and arms flexed forward
to 90 degrees. The patient should
be looking straight forward. The
lateral radiograph will document
the typical changes of Scheuermann
Õs kyphosis, such as SchmorlÕs
nodes, disk-space narrowing, irregular
endplates, and vertebral
Both the vertebral wedging and
the kyphosis should be measured
by the Cobb technique. For measuring
the kyphosis, the end vertebral
bodies, which are the last vertebral
bodies tilted into the kyphotic
deformity, should be selected. The
angle between the distal endplates
of these end vertebral bodies is the
kyphotic angle. When evaluating
serial radiographs to document true
progression, care should be taken to
ensure that the same end vertebral
bodies are being used. The angle
between the endplates of individual
vertebral bodies can be measured to
assess for vertebral wedging.
Wedging of at least 5 degrees of
three or more successive vertebral
bodies is essential to the diagnosis
of ScheuermannÕs kyphosis.
Variations of ScheuermannÕs
kyphosis do exist, and the diagnosis
of ScheuermannÕs kyphosis may
be expanded to allow for the presence
of a wider spectrum of the
disease. Bradford3 has stated that
the presence of one wedged vertebral
body suffices for the diagnosis
of ScheuermannÕs kyphosis. Patients
who present with irregular
endplate changes, disk-space narrowing,
and SchmorlÕs nodes without
vertebral wedging may have
another variation of ScheuermannÕs
kyphosis, as may patients with
fixed kyphosis but no other typical
radiographic findings.
The lateral radiograph should
also be used to evaluate other associated
conditions, such as hyperlordosis
of the lumbar spine,
spondylolisthesis, and degenerative
changes in the lumbar spine.
The anteroposterior radiograph is
used to assess the coronal balance
of the spine as well as the presence
of scoliosis, which is associated
with ScheuermannÕs kyphosis in
approximately a third of all patients.
To assess the flexibility of the
kyphosis, a lateral radiograph in
hyperextension may be obtained.
The same vertebral endplates used
to assess the standing lateral
kyphosis can be selected for the
hyperextension lateral view.
Radiography is the most helpful
tool in eliminating other elements
in the differential diagnosis and in
making the diagnosis of Scheuermann
Õs kyphosis. In both adolescents
and adults, postural kyphosis
is the most common entity in the
differential diagnosis. Postural
kyphosis is an increase in the thoracic
kyphosis of as much as 60
degrees. Radiographic findings
typical of ScheuermannÕs kyphosis
should not be found. In the adolescent,
the kyphotic angle should
be entirely correctable on hyperextension
Adolescent with kyphotic deformity.
The presence of congenital kyphosis
must be ruled out, particularly
in the adolescent. If an anterior
bar is present, ScheuermannÕs
kyphosis is effectively ruled out. In
the adult, other causes of fixed thoracic
kyphosis also exist: ankylosing
spondylitis, multiple healed
compression fractures, tumor,
infection, tuberculosis, and postlaminectomy
kyphosis. Computed
tomography, magnetic resonance
(MR) imaging, and myelography
may be helpful adjunctive studies
to complete the evaluation of the
kyphotic deformity.
Natural History
The natural history of Scheuermann
Õs kyphosis is difficult to discern.
It is generally agreed that
patients with mild deformities may
have few clinical sequelae. Those
patients who come to medical
attention typically do so because of
concern about deformity, pain,
cosmesis, or (rarely) neurologic
symptoms. Back pain and fatigue
in the adolescent may improve
with skeletal maturity. Back pain
in the adult patient with Scheuermann
Õs kyphosis is typically secondary
to spondylosis associated
with the deformity and is quite
often refractory to nonoperative
care. Paajaanen et al16 reported
that 55% of the disks in young
adults with ScheuermannÕs kyphosis
were abnormal on MR imaging.
This rate was five times that in
asymptomatic controls.
Murray et al5 reported on the
natural history and long-term follow-
up of ScheuermannÕs kyphosis
in 1993. They followed up 67
patients who had a mean kyphotic
angle of 71 degrees for an average
of 32 years and compared them
with age-matched controls. Patients
with ScheuermannÕs kyphosis
rated their back pain as more
intense and localized in the thoracic
spine. They had less demanding
jobs on average and less
extension of the thoracic spine
compared with controls. However,
both groups were similar in
terms of the level of education, the
number of days absent from work,
social limitations, use of medications
for back pain, and level of
recreational activities. The patients
in their series also reported
little preoccupation with physical
appearance. In regard to pulmonary
function, those patients
with kyphotic curves greater than
100 degrees had a higher incidence
of restrictive lung disease.
Other authors have encountered
more ominous results. Bradford17
reported the incidence of severe
pain over the thoracic spine in 50%
of his patients, with an increased
incidence of pain when the kyphosis
was centered over the upper
lumbar spine. Similarly, Lowe18
reported severe deformity and
back pain as common sequelae in
adults with untreated adolescent
ScheuermannÕs kyphosis.
In summary, there is a wide
variation in the natural history in
patients with ScheuermannÕs kyphosis.
There appears to be a subset
of patients with refractory
symptoms that warrant the
increased risk associated with
more aggressive treatments, such
as bracing and surgical management.
Treatment for patients with symptomatic
ScheuermannÕs kyphosis
ranges from observation to anterior
and posterior reconstructive surgery.
The recommended treatment
should be tailored to the individual
patient on the basis of the severity
of the curve and its consequent
Anti-inflammatory Medications
Anti-inflammatory medications
can be a useful short-term adjunct
to nonoperative care of the adolescent.
They may also be considered
for longer-term use for the adult
patient with low back pain associated
with spondylosis.
The use of exerciseÑspecifically,
extension or postural exercisesÑ
has never been demonstrated to
improve or halt progression of
fixed ScheuermannÕs kyphosis.
However, a thoracic extension program
combined with an aerobic
exercise program may improve
physical conditioning and ameliorate
associated pain. In the adult
patient with lumbar spondylosis,
spinal stabilization or even an
aggressive flexion program may be
added to the regimen to help manage
low back pain.
Brace Treatment
Brace treatment of Scheuermann
Õs kyphosis is typically reserved
for the adolescent patient
with growth remaining and thus
potential for correction of the
kyphosis. The indications for instituting
brace treatment vary. Sachs
et al12 used 45 degrees as a threshold
for initiating treatment.
The brace can be a Milwaukeestyle
brace, with a neck ring and
anterior and posterior uprights connecting
to a pelvic girdle. The
occiput should be padded off of the
neck ring, and there should be pads
in the posterior uprights overlying
the apex of the kyphosis. Accessory
pads can be added over the apex of
the scoliotic deformity, should one
coexist. The rods are straightened
and the pads are adjusted as correction
is obtained. Other styles of
braces are also available.
When a patient is fitted with a
customized Milwaukee brace, a lateral
radiograph is obtained to conClifford
firm proper fit of the brace as well
as the degree of correction. The
patient should then return to the
clinic in 3 to 4 weeks to again ensure
proper brace fitting. Lateral
radiographs should be obtained at
4- to 6-month intervals thereafter.
During bracing, physical therapy
may be initiated, including pelvictilt
exercises to reduce lumbar lordosis
as well as a thoracic extension
program. The brace should be
sequentially adjusted to maximize
After correction has been stabilized
and maximized and as skeletal
maturity approaches, a weaning
process from the brace can begin.
Lateral radiographs should be
obtained during the weaning
process, and any early loss of correction
should be addressed by
slowing the weaning process.
Bracing can be expected to provide
up to 50% correction of the deformity
while the brace is in place,
with a gradual loss of correction
over time. Sachs et al12 demonstrated
that of 120 patients followed
up for more than 5 years
after discontinuation of the brace,
69% still had improvement of 3
degrees or more from the initial
radiograph. Montgomery and Erwin19
demonstrated similar findings
in 21 patients treated with the
Milwaukee brace. The initial 21-
degree improvement while in the
brace had decreased to only 6
degrees at latest follow-up. However,
Sachs et al found that when
the presenting kyphosis was 74
degrees or more, brace treatment
failed in almost one third of cases,
necessitating surgical correction.
The role of bracing in the skeletally
mature patient with Scheuermann
Õs kyphosis is less clear. Bradford
et al20 reported in 1974 that
skeletal maturity is not necessarily
a contraindication to Milwaukeebrace
treatment and that partial
correction of the kyphosis could
sometimes be obtained. However,
bracing in the adult is often poorly
tolerated; perhaps its best niche is
in the patient with severe refractory
pain due to the kyphosis or lumbar
spondylosis who is nevertheless
not a surgical candidate.
Surgical Treatment
The operative indications for
patients with ScheuermannÕs kyphosis
are similar to those for
patients with other types of deformities:
progression of the deformity,
pain associated with the deformity,
neurologic compromise, and
cosmesis. An adolescent with
ScheuermannÕs kyphosis with a
curve of 75 degrees or more despite
appropriate bracing may be an
operative candidate. An adult with
ScheuermannÕs kyphosis may become
a surgical candidate when
severe refractory pain develops
secondary to the deformity, which
is generally of at least 60 degrees.
Neurologic compromise can also
become a surgical indication in
both adolescents and adults. The
perceived cosmetic benefit of
surgery cannot be underestimated
in dealing with either adult or adolescent
The goal of operative treatment
of ScheuermannÕs kyphosis is to
safely obtain a solid arthrodesis
throughout the length of the
kyphosis with correction of the
kyphotic deformity. This can be
obtained with a posterior-only
approach, an anterior-only approach,
or a combined anteriorposterior
approach .
The anterior-only approach, as described
by Kostuik,21 is an anteriorinterbody
fusion and anterior instrumentation
with a Harrington
distraction system augmented by
postoperative bracing. While the
authorÕs results in 36 patients were
good, with reduction of the mean
preoperative deformity of 75.5
degrees to an average of 60 degrees
at follow-up, the anterior instrumented
approach is not as widely
used for managing ScheuermannÕs
The posterior-only approach has
both advantages and limitations. It
offers decreased blood loss and
surgical time and avoids the risks
associated with a thoracotomy.
Reported disadvantages include a
higher rate of pseudarthrosis and
less correction. The posterior-only
approach remains the recommended
approach for patients with a
flexible deformity that corrects on
hyperextension to less than 50
degrees.22 For more severe deformities,
its use may be extended
with the addition of segmental fixation
and posterior facetectomy.
The anterior-posterior procedure
is reserved for patients with more
rigid deformities (typically 75
degrees or more) that do not correct
to less than 50 degrees on a hyperextension
lateral view. Recently, the
combined procedure has been more
commonly performed at one operative
sitting; however, some authors
still advocate a staged anteriorposterior
procedure. The anterior
approach may be performed either
open or thoracoscopically. The
anterior approach is typically performed
on the right to avoid the
great vessels. If a concomitant coronal
deformity is present, the approach
should be directed at the
convexity of the deformity. If a leftsided
approach is planned, preoperative
MR imaging is recommended
to assess the location of the great
vessels, which, if located posteriorly,
can obstruct a safe approach to
the thoracic spine.
The open approach is facilitated
by resecting a rib, which is later
used in performing the arthrodesis.
The rib level resected is that corresponding
to the most cephalad level
of the planned arthrodesis. Care
should be taken when planning this
approach, however. Radiographs
should be reviewed preoperatively
to evaluate the angle of the thoracic
ribs to the thoracic spine and thereby
to identify which rib should be
resected to facilitate the exposure.
An anterior release and interbody
fusion is performed on all levels
that are wedged or have a narrowed
disk space. A full anterior
release is performed, including
removal of the entire disk back to
the posterior longitudinal ligament
as well as resection of the anterior
longitudinal ligament.
The surgeon has two options for
performing the interbody fusion
technique. Structural rib graft may
be placed in each disk space, providing
support to the anterior column.
Alternatively, a trough can be
created in the lateral aspect of the
vertebral bodies, which is subsequently
filled with morseled bone.
This creates a column of graft that
will not dislodge during posterior
manipulation. The posterior procedure
can then be performed under
the same anesthetic or can be staged.
If the procedure is staged, the
patient can be mobilized out of bed
during the interim to prevent complications
associated with long-term
bed rest. Use of the Harrington
compression system for the posterior
instrumentation is well documented
in the literature. However,
segmental posterior systems (e.g.,
Cotrel-Dubousset, Texas Scottish-
Rite Hospital, and Isola) have
evolved to provide improved correction,
often obviating the need for
postoperative bracing or casting.
Posterior correction of the kyphotic
deformity can be performed
by one of two instrumentation
techniques: the compression technique
and the leverage technique.
The compression technique is a
four-rod construct in which two
upper rods are connected to two
distal rods by domino devices.
Compression is then applied over
the apex of the deformity through
the domino devices. This has the
net effect of shortening the posterior
column and reducing the kyphotic
The leverage technique is performed
by using two long posterior
rods with the planned correction
prebent into the rods. The rods are
attached either proximally or distally
by a claw technique. Additional
segmental hooks are then
progressively attached to the rod as
they are levered toward the spine,
thus reducing the deformity. This
technique has the advantage of
decreased hardware bulk over the
apex of the deformity.
Regardless of which technique is
employed, the compression technique
or the leverage technique,
Fig. 2 Anteroposterior (A)
and lateral (B) radiographs of
a 26-year-old man who presented
with a painful thoracic
deformity measuring 88
degrees from T2 to L1. Note
that the L1-2 disk is the first
lordotic disk (arrow). C,
Hyperextension lateral view
shows correction of the deformity
to 62 degrees. Planned
correction was an anterior
release and posterior instrumentation
to L1. Anteroposterior
(D) and lateral (E)
films obtained 1 year after an
anterior release and interbody
fusion, followed by a
posterior instrumented fusion
under the same anesthetic.
Thoracic kyphosis measured
48 degrees from T2 to

great care should be taking in
choosing fusion levels. The sagittal
balance should be assessed preoperatively
by dropping a plumb line
from the C7 vertebral body and
measuring the distance from the
sacral promontory to the plumb
line. If the plumb line falls anterior
to the promontory, the balance is
positive. Sagittal balance is often
negative in patients with severe
ScheuermannÕs kyphosis and is
typically exacerbated by surgical
correction of the kyphosis.
Overcorrection may lead to worsening
of sagittal balance and an
increased incidence of proximal
kyphosis. Proximally, the fusion
should be extended to the end vertebra
(i.e., the most cephalad vertebral
body that remains angulated into
the concavity of the deformity).
Distally, the instrumentation should
be extended beyond the end vertebral
body to the first lordotic disk
beyond the transitional zone. The
overall correction should not exceed
50% of the initial deformity or less
than 40 degrees. Adherence to these
guidelines, which were proposed by
Lowe and Kasten,23 should reduce
the risk for proximal and distal junctional
ScheuermannÕs thoracic kyphosis is
a structural deformity classically
characterized by anterior wedging
of at least 5 degrees of three adjacent
thoracic vertebral bodies.
Adolescents typically present to
medical attention with concerns
about cosmetic deformity; adults
more commonly present because of
increased pain. Progression of the
deformity, pain, neurologic compromise,
and cosmesis are the issues
that typically dictate treatment
options. In the adolescent, pain
associated with a kyphotic deformity
will usually respond to physical
therapy and anti-inflammatory
medications; a progressive curve
may be responsive to bracing. In
the adolescent or adult patient with
a progressive deformity, refractory
pain, or neurologic deficit, surgical
correction of the deformity may be
indicated. Surgical approaches
include a posterior-only approach
and a combined anterior-posterior
approach. Meticulous attention to
surgical technique is mandatory;
avoiding overcorrection and junctional
kyphosis by the appropriate
selection of fusion levels is of particular
1. S¿rensen KH: ScheuermannÕs Juvenile
Kyphosis: Clinical Appearances, Radiography,
Aetiology, and Prognosis. Copenhagen:
Munksgaard, 1964.
2. Fon GT, Pitt MJ, Thies AC Jr:
Thoracic kyphosis: Range in normal
subjects. AJR Am J Roentgenol 1980;
3. Bradford DS: Juvenile kyphosis, in
Bradford DS, Lonstein JE, Moe JH,
Ogilvie JW, Winter RB (eds): MoeÕs
Textbook of Scoliosis and Other Spinal
Deformities, 2nd ed. Philadelphia: WB
Saunders, 1987, pp 347-368.
4. Scoles PV, Latimer BM, DiGiovanni
BF, Vargo E, Bauza S, Jellema LM:
Vertebral alterations in ScheuermannÕs
kyphosis. Spine 1991;16:509-515.
5. Murray PM, Weinstein SL, Spratt KF:
The natural history and long-term follow-
up of Scheuermann kyphosis. J
Bone Joint Surg Am 1993;75:236-248.
6. Lowe TG: Scheuermann disease. J
Bone Joint Surg Am 1990;72:940-945.
7. Halal F, Gledhill RB, Fraser FC:
Dominant inheritance of Scheuermann
Õs juvenile kyphosis. Am J Dis
Child 1978;132:1105-1107.
8. Skogland LB, Steen H, Trygstad O:
Spinal deformities in tall girls. Acta
Orthop Scand 1985;56:155-157.
9. Lambrinudi C: Adolescent and senile
kyphosis. BMJ 1934;2:800-804.
10. Bradford DS, Brown DM, Moe JH,
Winter RB, Jowsey J: ScheuermannÕs
kyphosis: A form of osteoporosis?
Clin Orthop 1976;118:10-15.
11. Gilsanz V, Gibbens DT, Carlson M,
King J: Vertebral bone density in
Scheuermann disease. J Bone Joint
Surg Am 1989;71:894-897.
12. Sachs B, Bradford D, Winter R, Lonstein
J, Moe J, Willson S: Scheuermann
kyphosis: Follow-up of Milwaukeebrace
treatment. J Bone Joint Surg Am
13. Lings S, Mikkelsen L: ScheuermannÕs
disease with low localization: A problem
of under-diagnosis. Scand J Rehab
Med 1982;14:77-79.
14. Lonstein JE, Winter RB, Moe JH,
Bradford DS, Chou SN, Pinto WC:
Neurologic deficits secondary to
spinal deformity: A review of the literature
and report of 43 cases. Spine
15. Ryan MD, Taylor TKF: Acute spinal
cord compression in ScheuermannÕs
disease. J Bone Joint Surg Br
16. Paajaanen H, Alanen A, Erkintalo M,
Salminen JJ, Katevuo K: Disc degeneration
in Scheuermann disease. Skeletal
Radiol 1989;18:523-526.
17. Bradford DS: Juvenile kyphosis. Clin
Orthop 1977;128:45-55.
18. Lowe TG: Double L-rod instrumentation
in the treatment of severe kyphosis
secondary to ScheuermannÕs disease.
Spine 1987;12:336-341.
19. Montgomery SP, Erwin WE: Scheuermann
Õs kyphosis: Long-term results of
Milwaukee brace treatment. Spine
20. Bradford DS, Moe JH, Montalvo FJ,
Winter RB: ScheuermannÕs kyphosis
and roundback deformity: Results of
Milwaukee brace treatment. J Bone
Joint Surg Am 1974;56:740-758.
21. Kostuik JP: Anterior Kostuik-Harrington
distraction systems. Orthopedics
22. Bradford DS, Moe JH, Montalvo FJ,
Winter RB: ScheuermannÕs kyphosis:
Results of surgical treatment by posterior
spine arthrodesis in twenty-two patients.
J Bone Joint Surg Am 1975;57:439-448.
23. Lowe TG, Kasten MD: An analysis of
sagittal curves and balance after
Cotrel-Dubousset instrumentation for
kyphosis secondary to ScheuermannÕs
disease: A review of 32 patients. Spine

Osteogenesis Imperfecta

Osteogenesis Imperfecta

Dr Harry Sunaryo SpOT

Osteogenesis imperfecta (OI) is a
genetically determined disorder of
connective tissue characterized by
bone fragility. The disease state
encompasses a phenotypically and
genotypically heterogeneous group
of inherited disorders resulting
from mutations in genes coding for
type I collagen. Osteogenesis imperfecta
has been grouped clinically
with other heritable disorders of
connective tissue, including Ehlers-
Danlos syndrome, Marfan syndrome,
homocystinuria, Weill-
Marchesani syndrome, cutis laxa,
pseudoxanthoma elasticum, fibrodysplasia
ossificans progressiva,
and the chondrodysplasias, but
molecular studies are beginning to
allow more precise delineation.
Osteogenesis imperfecta is most
closely related to type VIIA and
type VIIB Ehlers-Danlos syndrome,
which also result from mutations in
type I collagen genes.
The clinical disease state is manifested
in tissues in which the principal
matrix protein is type I collagen
(mainly bone, dentin, sclerae,
and ligaments). The phenotypic
manifestations are variable in
severity, ranging from perinatal
lethal forms with crumpled bones
and severe deformity to clinically
silent forms with subtle osteopenia
and no deformity (Table 1). The
various classifications of OI will be
discussed in the ÒClassificationsÓ
section, but in general, clinical subtypes
represent a series of syndromes
related to classes of molecular
defects, each with a reasonably
well-defined phenotypic pattern.
Osteogenesis imperfecta is ubiquitous
in ethnogeographic distribution.
The prevalence of OI is approximately
16 cases per million
index patients. Sillence type I OI is
by far the most common clinical
subtype except in southern Africa,
where type III is more common.
The incidence of the mild type I
(tarda) form is estimated at 3 to 5
per 100,000; that of the severe
deforming type III form, 1 to 2 per

Osteogenesis imperfecta (OI) is a genetically determined disorder of connective
tissue characterized by bone fragility. The disease state encompasses a phenotypically
and genotypically heterogeneous group of inherited disorders that result
from mutations in the genes that code for type I collagen. The disorder is manifest
in tissues in which the principal matrix protein is type I collagen (mainly
bone, dentin, sclerae, and ligaments). Musculoskeletal manifestations are variable
in severity along a continuum ranging from perinatal lethal forms with
crumpled bones to moderate forms with deformity and propensity to fracture to
clinically silent forms with subtle osteopenia and no deformity. The differential
diagnosis includes other entities with multiple fractures, deformities, and
osteopenia. Classification is based on the timing of fractures or on multiple clinical,
genetic, and radiologic features. Molecular genetic studies have identified
more than 150 mutations of the COL1A1 and COL1A2 genes, which encode for
type I procollagen. Various systemic treatments have been attempted; however,
these interventions have been ineffective or inconclusive or are still experimental.
Gene therapy has the potential to increase the synthesis of type I collagen in mild
variants and to correct mutations in severe variants, but there are a great number
of technical difficulties to overcome. The goals of treatment of OI are to maximize
function, minimize deformity and disability, maintain comfort, achieve relative
independence in activities of daily living, and enhance social integration.
Attainment of these goals requires a team approach to tailor treatment needs to
the severity of the disease and the age of the patient. Nonoperative management
is the mainstay of orthopaedic treatment, with the goals of preventing and treating
fractures and enhancing locomotion. Operative intervention is indicated for
recurrent fractures or deformity that impairs function.

100,000 births; that of the lethal
perinatal type II (congenita) form, 1
per 40,000 to 60,000 births. The
intermediate type IV form is rare,
with an unknown frequency.1,2
The disease was first described
scientifically by Ekman in 1788,
who detailed involvement in four
generations of a family in Sweden
for his doctoral thesis. Since then,
more than 40 different names and
eponyms have been used, including
mollities ossium, fragilitas ossium,
osteopsathyrosis idiopathica,
osteomalacia congenita, osteoporosis
fetalis, Eddome syndrome, van
der Hoeve syndrome, Vrolik disease,
and Lobstein disease.1,2 The
term Òosteogenesis imperfectaÓ
was first used by Vrolik in 1849
when describing the pathologic
features of involved bone.
The disease likely dates back to
antiquity; an Egyptian mummy
from 1000 BC has been described as
having a wormian bone mosaic of
the skull, amber-colored teeth, and
severely bowed legs. It is speculated
that Ivar the Boneless, mastermind
behind the Scandinavian
invasion of England in the 9th century,
had OI. Legend has it that he
was unable to walk and was carried
into battle on a shield. Unfortunately,
his skeleton is not available,
as it was exhumed and burned by
William the Conqueror.1
Basic clinical and genetic studies
have identified the phenotypic characteristics
of OI, leading to the development
of classification schemes
and management strategies. More
recently, biochemical and molecular
genetic studies have characterized
many of the protein defects and collagen
mutations in OI, elucidating
the genotypic characteristics of this
disease. This article reviews the
clinical manifestations, diagnosis,
classification, molecular basis, and
management of OI.
Clinical Manifestations
Musculoskeletal System
The musculoskeletal features of
OI are variable in their extent and
severity, depending on the clinical
subtype and reflecting the underlying
genotypic heterogeneity. Gross
skeletal features include short
stature (with dwarfing in severe
forms), kyphoscoliosis, pectus
excavatum, and trefoil-shaped
pelvis with protrusio acetabuli.
The skull is often misshapen, with
a broad forehead, flattened posterior
cranium, overhanging occiput,
bulging calvaria, and triangular
facial shape. Depending on the
severity of disease, there may be
marked long-bone deformity with
anterior bowing of the humerus,
tibia, and fibula and lateral bowing
of the femur, radius, and ulna.
The overall incidence of spine
deformity in OI is approximately
60%, ranging from 90% for congenita
forms to 10% to 40% for tarda
forms.3 Thoracic scoliosis is the
most common deformity and arises
secondary to osteoporosis, compression
fractures, and ligamentous
laxity. The deformity of the thorax
associated with multiple rib fractures,
spinal deformity, molding of
Osteogenesis Imperfecta

Clinical Features and Classification of Osteogenesis Imperfecta
Sillence Shapiro
Type13 Type12 Type Features Inheritance
I Tarda B Mild form Blue sclerae, normal teeth (Sillence subtype IA) Autosomal dominant,
or dentinogenesis imperfecta (Sillence new mutations
subtype IB), mild bone fragility, fractures
after walking, minimal deformity
II Congenita A Lethal Blue sclerae, stillborn or neonatal death, Autosomal recessive,
perinatal numerous intrauterine fractures, new mutations,
crumpled long bones, severe deformity mosaicism
III Congenita B, Severe Normal sclerae, dentinogenesis imperfecta, Autosomal recessive,
tarda A deforming often fractures at birth, frequent fractures, new mutations,
frequent deformity, short stature, spine deformity mosaicism
IV . . . Intermediate Normal sclerae, normal teeth (Sillence subtype Autosomal dominant
form IVA) or dentinogenesis imperfecta (Sillence
subtype IVB), moderate bone fragility, moderate
deformity, short stature, phenotypic variability
the soft thorax, and pectus excavatum
or carinatum can be sufficiently
severe to compromise respiratory
function. Ligamentous laxity results
in hypermobile joints with
joint dislocations, patellar tendon
ruptures, and pes planus. There is
often a secondary muscular hypotonia
and underdevelopment related
to tendon or ligament anomalies
and reduced activity.
The hallmark of OI is bone
fragility. As with the other phenotypic
features of OI, the propensity
to fracture is extremely variable,
with manifestations ranging from
innumerable fractures in utero and
at birth to their virtual absence in
an adult. The timing and number
of fractures is included in some
classification schemes. In general,
the more severe forms of OI are
characterized by earlier and more
numerous fractures. These fractures
often occur after minor trauma
and can present with little pain.
Fractures generally heal with abundant
callus; however, the reparative
bone is also abnormal, and
fractures frequently lead to malunion
and pseudarthroses with
resultant long-bone deformity. The
incidence of fractures decreases
after puberty and rises again in
women after menopause and in
men after age 60.
The radiographic features of OI
are also proportional to disease
severity. The radiologic hallmark
of OI is diffuse osteopenia associated
with multiple fractures and
deformities. Generalized osteopenia
is seen in almost every case,
and there is often equal involvement
of the appendicular and axial
The long bones of the lower extremities
are usually more severely
affected than those of the upper
extremities. The long bones most
often appear slender; however, they
may show focal areas of thickened
cortices secondary to callus buttressing
or telescoping of fractures.
The metaphyses of the long bones
can be trumpet-shaped and cystic in
appearance. In severe cases, Òpopcorn
Ó calcifications appear in childhood
in the metaphyseal/epiphyseal
regions as displaced, fragmented
physeal cartilage undergoes
endochondral ossification. These
calcifications commonly resolve
after skeletal maturity, when all cartilage
is transformed to bone.
The vertebrae in OI often demonstrate
flattening or are biconcave
secondary to multiple microfractures.
Kyphoscoliosis often results.
The skull is characterized by
wormian bones, as first described
by the Danish anatomist Olaus
Wormius in 1643. This appearance
represents small, independent areas
of primary ossification within
membranous bones arranged in a
mosaic pattern .
Hyperplastic callus formation is
rare but can occur in patients with
OI. It often presents as pain, an
enlarging mass, and erythema, and
can be difficult to distinguish from
osteosarcoma radiographically,
clinically, and even histologically.
The histopathologic features of
OI also vary depending on disease
severity. Overall, there is a generalized
decrease in bone tissue, with
the bone structure demonstrating a
mixture of woven and lamellar patterns.
The histologic appearance of
bone in OI patients follows the normal
developmental and structural
pattern but rarely achieves the fully
compacted lamellar state. The more
severe the involvement, the more
immature the structural pattern. In
more severe forms of OI, the bone
appears histologically as a woven
bone matrix devoid of any organized
lamellar pattern .
There are plump osteoblasts crowded
along prominent osteoid seams,
large oval osteocytes surrounded by
small amounts of matrix, and morphologically
normal osteoclasts.
Histologic sections from patients
with less severe OI show a definite
tendency to lamellar bone formation
. The lamellation and
osteon formation can be rudimentary,
partially compacted, or fully
compacted in localized areas. Osteoid
seams are prominent, and
there is hypercellularity, with larger
than normal osteocytes and
osteoblasts in the areas of woven
bone. There is a correlation between
the degree of osteonal maturity
and bone strength as indicated
by ambulatory status.
The articular cartilage appears
normal. The physis often shows
disorganization of the proliferative
and hypertrophic zones with
increased permeation of cartilage
by metaphyseal blood vessels. The
metaphysis is composed of a
scanty, woven primary spongiosa.
There is increased bone turnover as
defined by tetracycline-labeling
studies. Callus bone is largely
woven. Ultrastructural studies
show a predominantly random
1 Anteroposterior (AP) skull radiograph
demonstrates wormian bone mosaic
arrangement of thinner collagen
fibers consistent with the lightmicroscopic
woven pattern.4,5
Other Systems
The effects of OI are not limited
to bone, but also involve tissues in
which the primary matrix protein
is type I collagen (dentin, sclerae,
skin, and ligaments). System involvement
(e.g., otologic, neurologic,
and respiratory) is secondary to
deformity and to primary metabolic
Dentinogenesis imperfecta is
characterized by soft, translucent
brownish teeth. The teeth are
affected in a nonuniform manner,
with involvement usually greater
in the primary teeth than in the secondary
teeth. The enamel wears
easily, and the teeth are carious,
shortened, and susceptible to
cracking. On x-ray films, the
crowns are bulbous, and there is
obliteration of pulp chambers.
About 30% of individuals with all
types of OI have significant dental
involvement. The Sillence classification
scheme subclassifies type I
and type IV OI on the basis of the
presence or absence of dentinogenesis
imperfecta. Dental treatment
includes crowning, dentures, and
intraosseous implants.
The blue sclerae in OI are the
result of increased corneal translucency
(secondary to abnormal collagen),
which reveals the underlying
uveal pigment and blood vessels.
This color changes with age,
becoming more grayish in adulthood.
The pericorneal region of the
sclera is often white and opaque,
resulting in a ÒSaturnÕs ringÓ
appearance, and there may be opacities
in the periphery of the cornea,
giving an arcus juvenilis appearance.
Hypermetropia is common.
The skin in OI is often thin,
translucent, and easily distensible,
resembling the atrophic skin of
elderly patients owing to collagen
insufficiency of the dermal layer.
Surgical scars commonly heal with
widening and prominence. Ligamentous
laxity is a characteristic
feature of OI. Pes planus is the
principal clinical manifestation, but
other disorders of hyperlaxity, such
as subluxating patellae and dysplastic
hips, are occasionally seen.
There is increased vascular fragility,
and a minority of patients demonstrate
nonprogressive aortic root
dilatation. Valvular disease, in particular
mitral valve prolapse, is
much less common than in Marfan
syndrome, but has been reported.6

Histologic appearance of bone specimens from patients
with OI of varying severity (hematoxylin-eosin; original magnification,
´65). Top left, Femoral cortex biopsy specimen
from a patient with type I OI demonstrates a near-normal
lamellar structure. Top right, Femoral cortex osteotomy specimen
from a patient with type III OI demonstrates a mixed pattern
of woven and lamellar bone. Bottom, Femoral cortex
specimen obtained at autopsy of a patient with type II OI
demonstrates a scanty, disorganized, woven matrix with large
The onset of hearing loss in OI
begins in adolescence and becomes
problematic for nearly 50% of
affected adults. It is seen primarily
in the type I benign autosomal
dominant variant. Hearing loss
can be conductive, sensorineural,
or mixed. The extent of deafness is
variable; however, loss in the highfrequency
range is characteristic.
Treatment usually involves prosthetic
stapedial footplate replacement
or stapedectomy. Other otologic
findings include recurrent
middle ear infections and sinusitis,
tinnitus from stapedial fixation,
vertigo from labyrinthine involvement,
and speech delay.
Intelligence is usually normal.
Low-pressure hydrocephalus can
be seen in some severe forms of OI.
The anterior fontanel remains
open, and there is general dilation
of the ventricles with cortical atrophy.
This process is usually selflimiting
and does not require
shunting. Basilar impression occurs
predominantly in Sillence type
III and type IV OI. There is brainstem
and spinal cord compression
at the foramen magnum, resulting
in progressive cerebellar disturbance
and lower cranial nerve dysfunction;
this may require cranial
decompression, which has had
variable results.
Metabolic abnormalities, present
to a variable extent in patients
with OI, are characterized by hypermetabolism,
heat intolerance,
elevated body temperature, increased
sweating, and resting
tachypnea and tachycardia. These
findings are generally attributed
to high metabolic activity and
turnover of the connective tissue
cells. Hyperthermia can occur
during anesthesia; rarely, true
malignant hyperthermia may
occur. There is evidence of uncoupling
of oxidative phosphorylation
in leukocytes and defects in platelet
adhesion and clot retraction in
patients with OI.7,8
The diagnosis of OI is still based
primarily on clinical and radiographic
criteria. Fibroblast cell culture
from skin biopsy specimens
can now be used to detect collagen
molecular abnormalities (discussed
in the ÒMolecular BasisÓ section) in
approximately 85% of patients with
OI. The differential diagnosis of OI
in infancy is relatively limited.
Hypophosphatasia presents with
multiple fractures, deformities, and
osteopenia. Other disorders, such
as achondrogenesis, achondroplasia,
pyknodysostosis, rickets, Menkes
syndrome, and homocystinuria,
have their own distinguishing
Diagnosis in childhood and adolescence
can be more difficult due
to less severe involvement. The
differential diagnosis includes
leukemia, fibrous dysplasia, and
idiopathic juvenile osteoporosis.
Idiopathic juvenile osteoporosis is
an extremely rare disorder with
onset at puberty. It is characterized
by generalized osteopenia and
propensity to fracture. Spontaneous
remission has been reported.
It can be distinguished from OI by
its onset in adolescence, the presence
of normal sclerae and teeth,
and a negative family history.
Hypophosphatasia resembles OI
with blue sclerae, bowing of legs,
and osteopenia; it can be differentiated
from OI by abnormal laboratory
findings such as the urine excretion
product phosphoethanolamine
and markedly decreased serum
alkaline phosphatase levels. Homocystinuria
is characterized by
osteoporosis, biconcave vertebrae,
and susceptibility to fracture; it can
be differentiated from OI by a marfanoid
habitus, ectopia lentis, and
abnormal urinary metabolites.
The distinction between mild
forms of OI and child abuse can be
difficult, but is crucial to consider.9
Both may present with a propensity
to fracture without a clear history
of definite trauma. Classically,
abuse presents with multiple fractures
in different stages of healing,
posterior rib fractures, metaphyseal
corner fractures, and skull fractures.
Other signs of abuse include
bruises, burns, and retinal hemorrhages.
Prenatal diagnosis of OI can be
made on the basis of structural
characteristics noted on fetal ultrasound,
collagen molecular studies
of cultured chorionic villus cells, or
genetic linkage studies with the use
of collagen markers.10 Prenatal
detection in pregnancies at risk for
OI can provide valuable information
for genetic counseling and
obstetric management. Ideally,
genetic counseling would provide
information concerning the likely
outcome of future pregnancies and
the prognosis for individual affected
children. In actuality, however,
this is difficult because of the high
incidence of spontaneous mutations
and sporadic cases, the lack of diagnostic
tests in the index case, and
the lack of an accurate carrier test.
Ultrasonography can effectively
screen fetuses for severe forms of
OI, but it remains difficult to detect
mild forms. Sillence type II OI can
be recognized on ultrasound scans
obtained before 20 weeksÕ gestation
by assessing femoral length adjusted
for gestational age, extent of
mineralization, evidence of fractures,
skull echogenicity, and thoracic
abnormalities. Midtrimester
ultrasonography is usually useful
in detecting type III OI by depiction
of intrauterine fractures and
deformity. Advances in transvaginal
ultrasound may provide a
means of first-trimester prenatal
diagnosis of severe forms of OI.
If a certain biochemical defect of
collagen or a specific mutation has
been identified in an affected parent
or sibling, prenatal detection
can be accomplished by screening
fetal tissue for the presence of that
defect. This is performed by culturing
chorionic villus cells and
examining the electrophoretic
properties of the collagen they produce.
Amniotic fluid cells are, in
general, not useful because most
cells synthesize a variant of type I
procollagen. Linkage studies performed
with the use of collagen
markers are currently the diagnostic
investigation of choice for families
with autosomal dominant OI,
allowing genotyping of the fetus.11
Clinical, radiographic, molecular,
and genetic studies support the
concept that OI is a syndrome with
several variants related to classes of
type I collagen mutations, each
with a reasonably well-defined phenotypic
pattern. As a result of the
extensive phenotypic heterogeneity
of OI, numerous classifications
have been proposed to categorize
clinical subtypes, provide a framework
for understanding the natural
history, and guide management.
Looser, in 1906, classified OI into
two types on the basis of when
the first fractures occurred: congenita
(fractures at birth) and tarda
(fractures after the perinatal period).
He noted that the prognosis in
the congenita type was poor, with a
high mortality rate. Seedorff, in
1949, further subclassified OI tarda
into gravis (fracture occurs within
the first year of life) and levis (fracture
occurs after the first year of
life), noting that tarda gravis was
associated with the development of
severe deformities and disability.
Shapiro,12 in 1985, revisited this
concept, defining natural history and
musculoskeletal prognosis on the
basis of the time of initial fracture
and the radiographic appearance of
the bones at the time of initial fracture.
Patients with the congenita
form have intrauterine or birth
fractures. Patients with the tarda
form sustain fractures initially after
birth. The congenita form of OI
was subdivided into type A (crumpled
femurs and ribs) and type B
(normal bone contours with intrauterine/
birth fractures). The tarda
form was subdivided into type A
(fractures before walking) and type
B (fractures after walking). At follow-
up in that study, patients in
the congenita type A group had a
mortality rate of 94%. Patients in
the congenita type B group had a
mortality rate of only 8%, with 59%
eventually becoming wheelchairbound
and 33% being ambulatory.
In the tarda type A group, 33% of
patients were wheelchair-bound,
and 67% were ambulatory. All
patients in the tarda type B group
were ambulatory.
The classification system currently
used most widely was developed
by Sillence in 1979 from a comprehensive
survey of patients in Australia.
The Sillence classification
divides OI patients into four types
on the basis of multiple clinical,
genetic, and radiologic features
Type I OI is the
mildest and most common form.
Inheritance is autosomal dominant,
although new mutations are frequent.
Type I is subclassified into
the more common type A (without
dentinogenesis imperfecta) and the
less common type B (with dentinogenesis
imperfecta). The sclerae are
blue, and the first fractures usually
occur in the preschool years, after
walking has begun. There is commonly
absence of significant deformity;
kyphoscoliosis is comparatively
mild and uncommon; and stature
is generally normal. Life expectancy
is normal for patients with type IA
OI and only marginally impaired for
those with type IB. Socially, type I
OI patients are scarcely distinguishable
from the normal population,
with most fully employed and living
Type II OI is the lethal
perinatal form.

Six-week-old neonate with lethal perinatal type II OI who died at 12 weeks due
to respiratory failure. Features included blue sclerae, short stature, and short, deformed
extremities. B, Lateral lower-extremity radiograph of another child with type II OI shows
osteopenia, short crumpled femurs, multiple fractures, and deformity.
stillborn, and survivors are often
born prematurely. The disorder is
usually lethal within the first few
weeks of life, but some affected
infants survive for several months,
and a few live for one or more
years. Death is generally due to
respiratory failure, intracranial
hemorrhage, or brainstem compression.
The sclerae tend to be blue or
grayish. There are multiple intrauterine
fractures, and the femurs,
tibias, and ribs are short, broad,
crumpled, and deformed. Inheritance
was thought to be autosomal
recessive; however, most cases
appear to result from new dominant
mutations in a proband of
unaffected parents. Occasionally,
unaffected parents have multiple
affected children; this is thought to
result from parental mosaicism or
to be due to a rare autosomal recessive
Type III OI is the severe deforming
form, with fractures generally
present at birth (Fig. 4). The sclerae
are generally normal in color.
Frequent fractures and deformity
are common, stature is typically
severely shortened, and the spine is
often deformed (Fig. 5). Respiratory
complications and dentinogenesis
imperfecta are common. Inheritance
is thought to be autosomal
recessive; however, new dominant
mutations are common, and a rare
autosomal dominant variety exists.
Life expectancy is decreased, but
affected individuals live into adulthood.
Early mortality is due to respiratory
illness, injury with intracranial
hemorrhage, and basilar
Type IV OI is a moderately
severe form with great phenotypic
variation, but is usually intermediate
in severity between type III and
type I. This variant is infrequent,
accounting for approximately 5% of
cases. Sclerae are normal, short
stature is variable, dentinogenesis
imperfecta is common, and fractures
and deformity are relatively
common. Inheritance is autosomal
dominant. Life expectancy can be
decreased depending on disease
severity; however, a large percentage
of patients function independently
well into adulthood.
The Sillence classification correlates
with the congenita/tarda temporal-
radiographic Shapiro groups.
The congenita A group encompasses
Sillence type II lethal perinatal
patients; congenita B and tarda A
are generally Sillence type III
patients with progressive deformity;
and tarda B represents the
Sillence type I benign autosomal
dominant patients.
Molecular Basis
Studies examining the skin of
patients with OI in the 1960s and
1970s gave the first clear indication
of collagen abnormalities. Subsequently,
skin fibroblast cell culture
studies have confirmed that the
cells of affected individuals produce
either decreased amounts of
collagen or defective collagen.
Detailed biochemical investigations
have demonstrated heterogeneity
of type I collagen defects.
Radiograph of a newborn with type III OI. Features include osteopenia and a fracture
of the left femur.
Four-year-old child with type III
OI. Features include a broad flattened
forehead, short arms, and short stature.
She has undergone osteotomies with
intramedullary rodding of her lower
extremities and ambulates with braces and
a walker.
Recently, molecular biology studies
have defined more than 150
specific gene mutations that result
in OI, and investigations to characterize
the mechanisms that translate
these mutations into the various
observed phenotypes are
Osteogenesis imperfecta is
caused by mutations in the
COL1A1 (18-kilobase [kb] size,
located on the long arm of chromosome
17) and COL1A2 (38-kb size,
located on the long arm of chromosome
7) genes that encode the two
pro-a1(I) and one pro-a2(I) chains
of the type I procollagen trimer,
respectively. These genes contain
more than 50 exons to generate
about 1,450 amino acids of each
chain. The formation of the essential
triple helical structure of procollagen
I from these three pro-a(I)
chains depends on the presence of
glycine in every third position in
the 1,014-residue triple helical
domain and is stabilized by the
presence of hydroxyproline. The
triple helix is propagated from the
carboxyl-terminal end toward the
amino-terminal end of the molecule.
The mature molecule is then
secreted from the cell into the extracellular
matrix, where the aminoterminal
and carboxyl-terminal
propeptides are removed enzymatically
and type I collagen fibrillogenesis
occurs by self-assembly.2,15-18
More than 150 mutations of the
COL1A1 and COL1A2 genes, including
single base-pair changes,
deletions, insertions, premature
stop codons, and splicing mutations,
have been described, causing
forms of OI ranging in phenotype
from mild to lethal. The most frequent
mutation types are single
base-pair substitutions in either of
the two alleles that alter a codon
for glycine in the triple helical
domain of the chain.
The molecular basis of Sillence
type I OI remains poorly understood.
Cells from affected individuals
largely demonstrate a quantitative
defect of type I collagen; they
synthesize and secrete about half
the normal amount of type I procollagen.
This is due to decreased
synthesis of pro-a1(I) chains; in
general, the pro-a2(I) chain is normal.
The mutation often occurs in
one allele, resulting in about half
the normal amount of the molecule,
as type I procollagen must
contain two pro-a1(I) chains.
The vast majority of infants with
type II OI appear to be heterozygous
for mutations that result in
substitutions for glycine residues
within the triple helical domain of
either the pro-a1(I) or the pro-a2(I)
chain. In some instances, exonskipping
mutations in either gene
can result in this phenotype. Type
III and type IV phenotypes can also
result from heterozygosity for point
mutations of glycine residues within
the triple helical domains of
either chain of type I procollagen or
from exon-skipping mutations.2,15-18
There are several basic concepts
concerning the nature of mutations
and their phenotypic consequences.
Quantitative mutations
that decrease expression and synthesis
of normal type I procollagen
molecules result in milder phenotypes,
such as type I OI. Qualitative
mutations that lead to structural
aberrations and abnormal
type I procollagen result in more
severe phenotypes, such as types II
and III. The severity of the phenotype
reflects the location of the
mutation within the chain, the
nature of the mutation, and the
chain in which the mutation occurs.
In general, with point mutations,
the phenotype becomes
milder as the mutation is shifted
toward the amino-terminal end of
the chain, because the essential
triple helical structure is formed
from the carboxyl-terminal end
toward the amino-terminal end in
a zipperlike helical-coiling manner.
With glycine substitution mutations,
amino acid replacements
with bulkier side chains, such as
arginine, result in more severe
phenotypes than those with smaller
side chains, such as serine and
cysteine. Mutations in the
COL1A2 gene have milder consequences
than similar mutations in
the COL1A1 gene, as the type I
procollagen molecule has two proa1(
I) chains and one pro-a2(I)
The expression of these mutations
into the observed phenotypic
patterns is poorly understood. On
the molecular level, these mutations
can decrease the rate of synthesis,
decrease the thermal stability
of the triple helical molecules,
delay the rate of folding of the precursor
procollagen molecule,
increase the level of aberrant posttranslation
modification of procollagen
chains, and impair the rate of
export of molecules from cell to
matrix. Mutated chains are more
slowly incorporated into fibrils
than normal collagen molecules;
demonstrate an abnormal configuration,
with more branching, shortening,
or thickening; and impair
mineralization by providing a
mutated structural template for
incorporation of hydroxyapatite
crystals. The end result of these
molecular changes eventually
translates into the microscopic and
gross pathologic features characteristic
of OI.2,15-19
The identification of a vast array
of genetic mutations associated
with OI is commensurate with the
observed phenotypic heterogeneity
of this disease. This supports the
concept that OI represents a continuum
of mutational events translating
into a continuum of phenotypic
involvement from perinatal lethal
forms to moderate deforming forms
to mild, nondeforming forms.
Included in this continuum would
be type VII Ehlers-Danlos syndrome
and some variants of osteoporosis.
In type VIIA and type VIIB

Ehlers-Danlos syndrome, the molecular
abnormality is impaired
cleavage of the N-terminal propeptides
from procollagen secondary to
mutations in the COL1A1 and
COL1A2 genes. Phenotypically,
this results in joint hypermobility,
skin changes, and other signs of
connective tissue involvement.
Thus, any classification system of
OI must impose arbitrary boundaries
within this continuum. However,
for purposes of facilitating
communication, predicting natural
history, and planning management
strategies, it seems reasonable to
continue classifying into clinical
subtypes, such as the Sillence classification
or the congenita-tarda
schemes. These groupings represent
a series of syndromes related
to classes of molecular defects, each
with a reasonably well-defined phenotypic
Systemic Therapy
Several systemic treatments for
OI have been attempted, but all
have been ineffective or inconclusive
or are still experimental. Two
features of OI make evaluation of
the efficacy of therapeutic interventions
difficult. First, the large
genetic and biochemical heterogeneity
in OI results in trials that
combine patients with different
mutations. Thus, a treatment that
may benefit individuals with specific
mutations and biochemical
defects may be ineffective for other
patients with different mutations
and biochemical defects. Second,
the frequency of fractures within
the same patient can differ dramatically
from one time period to
another. Thus, studies that use
fracture frequency or linear growth
to evaluate efficacy without wellmatched
controls may show
improvement unrelated to drug
Calcitonin has been used because
of its osteoclastic inhibitory
effects and resultant increase in
bone density in osteoporosis. Results
in patients with OI have been
mixed, with some studies finding
decreased fracture frequency and
increased bone density, and other
studies finding no effect and high
side-effect profiles. Similarly,
sodium fluoride, calcium, anabolic
steroids, growth hormone, magnesium
oxide, vitamin C, and vitamin
D have been tried in OI patients
with mixed results and failure
to demonstrate definite treatment
value. The efficacy of bisphosphonates
in increasing bone mineral
content and density while reducing
bone resorption in patients
with OI has not yet been established.
Although still strictly theoretical,
conceivably the most dramatic and
efficacious form of treatment for OI
and related disorders would be gene
therapy. In Sillence type I OI, this
could involve stimulation of type I
collagen synthesis. In the more
severe types, this could involve
replacement of the defective gene.
In one series of experiments, researchers
developed a modified
oligonucleotide that specifically
inhibited expression of a mutated
gene for the pro-a1(I) chain of type I
procollagen by 50% to 80% in cell
culture studies. There are considerable
technical barriers involved in an
oligonucleotide design and delivery
system in vivo; however, the potential
optimal effect may be to convert
a severely debilitating phenotype to
a milder form of the disease through
inhibition of expression.2,15 In another
series of experiments, researchers
developed a transgenic
mouse line that expressed an antisense
RNA for the pro-a1(I) chain.
When bred to mice that expressed a
phenotype of severe brittle bones,
offspring that expressed both genes
had a marked decrease in lethality
and an increase in the incidence of
brittle bones, presumably because
they had a rescue phenotype.2,15
Orthopaedic Management
The overall goals of treatment of
OI are to maximize function, minimize
disability, achieve relative independence
in activities of daily living,
attain the greatest possible degree of
mobility, allow social integration,
and maintain overall health. This
requires a team approach from the
health-care providers, including the
pediatrician, orthopaedic surgeon,
geneticist, neurologist, neurosurgeon,
dentist, ophthalmologist,
physical therapist, social worker,
and nurse-clinician. Care must be
individualized, depending primarily
on the severity of the disease and the
age of the patient. Sillence type I OI,
in its milder forms, may have only a
minimal impact on the patient, and
the role of the orthopaedic surgeon is
limited to conventional fracture care.
Early death often occurs in type II OI
before any orthopaedic intervention
is indicated. Type III and type IV
present the greatest management
challenges for the orthopaedist in
terms of fracture prevention, fracture
management, limitation of deformity,
and optimization of function.20-22
The management of OI begins
with early detection in utero for
pregnancies at risk to guide in family
planning and obstetric management.
In the neonate with deforming
OI (type III and some type IV),
immediate life-threatening problems
of respiratory insufficiency
and intracranial hemorrhage are
managed by the neonatologist. In
utero fractures have usually healed,
and recent fractures often do not
require special treatment other than
splinting. The parents should be
educated about handling of the
infant and about the natural history
of the disease. Lay organizations,
such as the OI Foundation, are
helpful with parental education.
In infancy and childhood, physical
therapists can be instrumental
Mininder S. Kocher, MD, and Frederic Shapiro, MD
Vol 6, No 4, July/August 1998 233
in optimizing normal development
patterns as the infant develops
trunk control and functional limb
use. The orthopaedist is involved
in helping to obtain the greatest
degree of mobility possible and in
the treatment of fractures, which
can be frequent. When fractures
occur, one should use as little
immobilization as possible to prevent
overall deconditioning, worsening
the extent of osteopenia, and
increasing the risk of further fracture.
In severe OI, the multiplicity
of fractures, the underlying osteoporotic
bone, and the abnormal
mechanical stresses on malaligned
bones can lead to further fractures
and deformity, interfering with the
ability to stand and walk. External
support from orthoses or splints
may be necessary to optimize function.
Deformity that is impairing
function can be addressed surgically
by multiple osteotomies and
intramedullary fixation.
Fracture rates almost always decrease
dramatically after puberty,
but increases have been documented
in women after menopause and
in men after age 60. Pregnancy in
women with OI requires special
obstetric management due to
increased fracture risk, pelvic dysplasia,
and metabolic abnormalities.
Nonoperative treatment is the
mainstay of orthopaedic management
of OI. Depending on disease
severity, a comprehensive and progressive
program of mobilization
and bracing is pursued for patients
with ambulatory potential, and a
program of appropriate seating and
wheelchair locomotion is pursued
for nonambulatory patients. The
goal is to emphasize ultimate independent
function and to maximize
social integration.20-22 Lightweight
bracing can be helpful for external
structural support to promote
stance and locomotion and for the
prevention and treatment of fractures.
Pneumatic trouser splints
and vacuum pants have been introduced
to support fragile bones,
improve mobility, and maintain
alignment after fracture or closed
Closed treatment methods are
the mainstay of fracture management.
Fractures generally heal,
often with exuberant callus but
with the same abnormal bone quality.
The difficulty in fracture management
lies in the prevention of
deformity and the vicious circle
associated with immobilizationÑ
deconditioning, osteoporosis, and
increased fracture risk. Lightweight
splints and braces are most
often used, with the emphasis on
early mobilization.
Operative intervention is indicated
for recurrent fractures or
deformity that impairs function.
The optimal age for surgical intervention
is controversial; some recommend
early intervention with
elongating rods, but traditional
management involves accepting
deformity from closed treatment
until the patient is about 5 years
old and then proceeding to corrective
Various techniques for deformity
correction have been espoused,
including closed osteoclasis with
traction followed by pneumatic
splints (Morel technique), closed
osteoclasis with percutaneous
intramedullary nailing,24 multiple
corrective osteotomies with
intramedullary nailing (Sofield-
Millar technique)25,26 , and
osteotomies with elongating intramedullary
(Bailey-Dubow) rods.27,28

Leg deformity in a patient with type III OI. A, Preoperative AP radiograph
obtained at age 6 years demonstrates deformity. B, Postoperative film with leg in cast
shows multiple osteotomies (arrows) with intramedullary fixation. C, Film obtained after
healing of osteotomies.
Management must be highly individualized,
taking into account
personal experience, the severity of
the patientÕs deformity, the diameter
of the long bones, and the
advantages and complications of
each technique. Elongating rods
have a decreased replacement rate
when compared with nonelongating
rods; however, they are weaker;
traverse the physis; are technically
more demanding, as they
require a larger medullary canal
and central placement; and are
associated with complications
related to disassembly and nonelongation.
General principles in the surgical
management of OI include avoiding
surgery in patients under age 2
years, avoiding plate-and-screw fixation
in favor of intramedullary fixation,
and use of gentle technique
for muscle preservation and minimization
of soft-tissue bleeding.
Bone-holding clamps should be
avoided, as they can crush fragile
bone. Radiographic control is
essential, as the deformities are
often three-dimensionally complex,
necessitating different views.
When multiple osteotomies are
performed, the individual fragments
should be as long and
straight as possible. Placement of
osteotomies in diaphyseal regions
enhances stability with intramedullary
rods. Some bone shortening
may be necessary when there
are severe deformities, as the taut
soft-tissue structures on the concave
side can be stretched excessively
when deformity is corrected.
Reaming may occasionally be necessary
for rod placement. Violation
of the growth plate should be
avoided when possible. Immobilization
with casting or braces until
bone union is almost always necessary.
The anesthesiologist should be
aware of the increased risk of
malignant hyperthermia in patients
with OI. Anesthetic principles
include avoiding the use of atropine,
careful metabolic monitoring,
not insulating the patient with
large numbers of drapes, and
aborting the operation at the earliest
signs of hyperthermia.8 Patients
with OI may have platelet
and coagulation abnormalities, and
perivascular fragility due to collagen
abnormalities may predispose
to bleeding. Blood loss and insensible
losses due to hypermetabolism
should be carefully monitored.
Spinal deformity in patients with
OI is difficult to manage. Truncal
shortening of thoracolumbar spinal
segments can occur secondary to
collapse of osteopenic vertebrae. If
the patient is symptomatic, a soft
spinal orthosis is helpful. Scoliotic
and kyphoscoliotic curves often
progress rapidly. The soft, deformed
rib cage and truncal shortening
combine to render bracing
relatively ineffective, but it can be
helpful in mild forms of OI and as a
sitting aid for the nonambulator.
In milder forms of OI, bracing
can be utilized for curves of 20 to
40 degrees or kyphosis greater than
40 degrees. Spinal fusion has been
recommended for scoliotic curves
greater than 45 degrees to halt progression
(Fig. 7). For patients with
more severe involvement, bracing
is ineffective and can produce thoracic
cage deformity; fusion is recommended
for curves over 35
degrees, as these curves are most
often progressive and potentially
severe. There is a high incidence of
complications from spinal fusion in
OI, because internal fixation is limited
by poor bone quality, autogenous
iliac-crest bone graft is limited,
and patients have a propensity
to bleeding.3,29
Osteogenesis imperfecta is a remarkable
disorder. Recent clinical,
genetic, and molecular investiga-
Rapidly progressive spinal deformity in a 12-year-old child with type III OI. A,
Preoperative AP radiograph shows a 90-degree right thoracic curve with severe rib deformities
at the curve concavity. B, AP film obtained after spinal fusion with Luque instrumentation.
tions have characterized its heterogeneous
phenotypic and genotypic
features. In addition, insight has
been gained from investigations
into the altered collagen chemistry
and its effect on the structure and
function of bone.
Ongoing research holds great
promise for the treatment of OI. The
potential for gene therapy to increase
the synthesis of type I collagen
in mild variants and to correct
mutations in severe variants lies
ahead, but there are a great number
of technical difficulties to overcome.
Further understanding of how genotypic
mutations lead to abnormal
molecular structure and then abnormal
bone structure is essential.
As long as the potential for gene
therapy remains distant, welldesigned
controlled trials with systemic
treatment modalities are
needed. Ideally, these would direct
specific interventions to patients
with particular biochemical abnormalities,
recognizing the underlying
heterogeneity of the disorder.
The development of registries
including both phenotype and
genotype would catalog this new
classification of patients and would
facilitate defect-specific trials.
Development of comprehensive
treatment teams to address the
multiple health-care needs of OI
patients will ultimately help them
achieve goals of relative independence
and social integration.

1. Tsipouras P: Osteogenesis imperfecta,
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Disorders of Connective Tissue, 5th
ed. St Louis: Mosby-Year Book, 1993,
pp 281-314.
2. Byers PH, Steiner RD: Osteogenesis
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3. Benson DR, Newman DC: The spine
and surgical treatment in osteogenesis
imperfecta. Clin Orthop 1981;159:
4. Bullough PG, Davidson DD, Lorenzo
JC: The morbid anatomy of the skeleton
in osteogenesis imperfecta. Clin
Orthop 1981;159:42-57.
5. Falvo KA, Bullough PG: Osteogenesis
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Bone Joint Surg Am 1973;55:275-286.
6. Wong RS, Follis FM, Shively BK,
Wernly JA: Osteogenesis imperfecta
and cardiovascular diseases. Ann
Thorac Surg 1995;60:1439-1443.
7. Cropp GJA, Myers DN: Physiological
evidence of hypermetabolism in osteogenesis
imperfecta. Pediatrics 1972;49:
8. Libman RH: Anesthetic considerations
for the patient with osteogenesis
imperfecta. Clin Orthop 1981;159:
9. Carty HML: Fractures caused by child
abuse. J Bone Joint Surg Br 1993;75:
10. Cole WG, Dalgleish R: Perinatal lethal
osteogenesis imperfecta. J Med Genet
11. Sykes B, Ogilvie D, Wordsworth P, et
al: Consistent linkage of dominantly
inherited osteogenesis imperfecta to
the type I collagen loci: COL1A1 and
COL1A2. Am J Hum Genet 1990;46:
12. Shapiro F: Consequences of an osteogenesis
imperfecta diagnosis for survival
and ambulation. J Pediatr Orthop
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Genetic heterogeneity in osteogenesis
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An expanding panorama of variants.
Clin Orthop 1981;159:11-25.
15. Prockop DJ, Kuivaniemi H, Tromp G:
Molecular basis of osteogenesis imperfecta
and related disorders of bone.
Clin Plast Surg 1994;21:407-413.
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in a wide spectrum of diseases.
Ann Med 1993;25:113-126.
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of heritable connective tissue diseases.
J Pediatr Orthop 1993;13:392-403.
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Tracing the pathway between mutation
and phenotype in osteogenesis
imperfecta: Isolation of mineralizationspecific
genes. Am J Med Genet 1996;
19. Sztrolovics R, Glorieux FH, Travers R,
van der Rest M, Roughley PJ: Osteogenesis
imperfecta: Comparison of
molecular defects with bone histological
changes. Bone 1994;15:321-328.
20. Bleck EE: Nonoperative treatment of
osteogenesis imperfecta: Orthotic and
mobility management. Clin Orthop
21. Gerber LH, Binder H, Weintrob J, et al:
Rehabilitation of children and infants
with osteogenesis imperfecta: A program
for ambulation. Clin Orthop
22. Albright JA: Management overview of
osteogenesis imperfecta. Clin Orthop
23. Letts M, Monson R, Weber K: The
prevention of recurrent fractures of the
lower extremities in severe osteogenesis
imperfecta using vacuum pants: A
preliminary report in four patients. J
Pediatr Orthop 1988;8:454-457.
24. Stoltz MR, Dietrich SL, Marshall GJ:
Osteogenesis imperfecta: Perspectives.
Clin Orthop 1989;242:120-136.
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Osteoporosis: The Role of the Orthopaedist

Harry Sunaryo SpOT

Osteoporosis ranks as a major health
problem affecting more than 25 million
Americans and leading to more
than 1.5 million fractures each year.
One of every two women over the
age of 50 years will have an osteoporosis-
related fracture, and one in
every three men over the age of 75
years will be affected by this disease.
A single hip fracture is estimated to
cost between $26,000 and $30,000,
and the overall cost of acute and longterm
care associated with osteoporosis
exceeds $10 billion annually.1
Because a substantial number of
patients will encounter an orthopaedist
for an osteoporosis-related
problem, an understanding of
the pathophysiology, diagnostic
approach, and medical and surgical
treatment options is essential. This
article will provide a summary
update for each of these issues, as
well as a discussion of preventive
strategies that the orthopaedist can
offer to patients who may be at risk
for developing this disease.
Defining the Problem
Osteoporosis is a disease characterized
by low bone mass, microarchitectural
deterioration of bone tissue
leading to bone fragility, and a consequent
increase in fracture risk.
Although fractures of the spine, hip,
and wrist are most typical of this
condition, fractures of other bones,
such as the ribs, humerus, and
pelvis, are not uncommon.1
Two categories of osteoporosis
have been identified: primary and
secondary. Primary osteoporosis is
by far the more common form of
the disease and includes postmenopausal
osteoporosis (type I);
age-associated osteoporosis (type
II), previously termed senile osteoporosis,
which affects a majority of
individuals over the age of 70 to 80
years; and idiopathic osteoporosis, a
disorder of unknown cause that
affects premenopausal women and
men who are middle-aged or
younger. In secondary osteoporosis,
loss of bone is caused by an
identifiable agent or disease process,
such as an inflammatory disorder, a
disorder of bone marrow cellularity,
corticosteroid use, or a disorder of
endocrine control of bone remodeling
.2 It is important to recognize
that the type I and type II
variants of primary osteoporosis are
not mutually exclusive. On the contrary,
patients who have one type of
osteoporotic fracture are likely to
have another osteoporotic fracture
of a different type.2
Osteoporosis reflects the inadequate
accumulation of bone tissue
during growth and maturation,
excessive losses thereafter, or both.
Since residual bone density is the net
result of these factors, and since
there are no safe, effective ways to
rebuild the osteoporotic skeleton,
prevention emerges as the crucial
strategy.1 Consequently, a knowledge
of preventive approaches is
essential, including awareness of the
efficacy and safety of estrogen and
progestin therapy, intake of calcium
and other nutrients, exercise, calcitonin,
bisphosphonates, and other
modalities on the horizon. Prevention
also requires an understanding
of predictive factors, so that the likelihood
of osteoporosis can be judged
and an awareness of indications for
estimating bone density can be
developed .
Bone Metabolism and
Regulation of bone metabolism
depends on the delicate balance

Osteoporosis is one of the most prevalent musculoskeletal disorders encountered
in orthopaedic practice today. This review provides an update on the pathophysiology
of bone metabolism leading to osteoporosis, describes the latest methodology
in the diagnostic workup of patients with low bone mass, and summarizes the current
status of osteoporosis treatment regimens. The special needs of the osteoporotic
fracture patient are also addressed. In general, load-sharing devices and
sliding nail-plate constructs are preferred over rigid internal-fixation systems.
Prolonged immobilization should be avoided
between the functions of several
endocrine organs and their effects on
the cell types found in bone
(osteoblasts, osteoclasts, and osteocytes).
Endocrine organs that are
important to bone metabolism
include the skin, parathyroid
glands, liver, kidneys, gonads,
adrenals, and thyroid. In addition, in
certain pathologic states, pituitary
and hypothalamic function also
affect bone physiology. The activities
of the endocrine system as they
apply to bone are to maintain normal
serum calcium levels.
Vitamin D
Vitamin D modulates calcium homeostasis,
either directly or by affecting
various calcium-regulating cell
systems. In Caucasian persons, 15
minutes of exposure to bright sunlight
on the hands and face per day
produces enough vitamin D3 (cholecalciferol)
to satisfy the minimum
requirement (10 mg) of this hormone.
Dark-skinned persons may
require longer exposure. The major
source of vitamin D is the diet, which
provides vitamin D2 (ergocalciferol).
All vitamin D metabolites are fat-soluble
vitamins. Because some individuals
may lack sufficient exposure
to sunlight as well as dietary exposure
to foods naturally containing
vitamin D, most milk in the United
States is supplemented with vitamin
D2. The only significant natural
source of vitamin D is cod liver oil.3
In vitamin D metabolism, precursor
molecules are converted to the
active form. After formation in the
skin, cholecalciferol circulates to the
liver, where it is hydroxylated to produce
the major circulating prohormone,
(calcifediol). Conditions that affect
hepatic function and drugs that
induce P-450 microsomal enzymes
(e.g., phenytoin) will interrupt this
conversion pathway and lead to the
production of inactive polar metabolites
of cholecalciferol.3 These conditions
can increase the risk of osteoporosis
and, if severe, can lead to various
forms of osteomalacia.
The next step in the metabolism of
vitamin D is the 1a-hydroxylation of
25-hydroxycholecalciferol to form
1,25-dihydroxycholecalciferol (calcitriol)—
the physiologically active
form of the vitamin. The enzyme for
this reaction, located in the mitochondria
of renal tubular cells, is
activated by parathyroid hormone.
Although parathyroid hormone is
the major molecule that controls 1a-
hydroxylase function, phosphate,
ionized calcium, and specific levels
of 1,25-dihydroxycholecalciferol
itself can regulate this activity.4
The major target tissues of 1,25-
dihydroxycholecalciferol are bone,
kidney, and intestine. In the kidney,
it increases proximal tubular reabsorption
of phosphate. It also acts as
a feedback regulator of its own formation.
In the intestine, calcitriol
induces production of the critical
calcium-binding protein responsible
for active calcium transport.3
The physiologic role of vitamin D
is less well understood. At pharmacologic
doses, it accelerates bone
resorption by increasing the activity
and number of osteoclasts. However,
vitamin D probably modulates
bone physiology by acting on the
osteoblast. The osteoblast then
influences the osteoclast via
cytokines acting as regional second
Parathyroid Hormone
Parathyroid hormone and vitamin
D together form a parathyroid hormone–
axis, which is the major metabolic regulator
of calcium and phosphate
fluxes in the body.4 The three major
target organs of parathyroid hormone
are bone, kidneys, and intestines.
In bone, parathyroid hormone is
generally regarded as a boneresorbing
hormone. However,
receptors for parathyroid hormone
Age, yr
Sex ratio (F:M)
Type of bone loss
Fracture site
Main causes
Mainly trabecular
Vertebrae (crushed), distal
radius, hip (mainly
Factors related to menopause
Trabecular and cortical
Vertebrae (multiple wedged),
hip (mainly femoral neck)
Factors related to aging
Type I
Feature (Postmenopausal)
Table 1
Types of Involutional Osteoporosis
Type II
Genetic and biologic
Family history
Fair skin and hair
Northern European background
Osteogenesis imperfecta
Early menopause
Slender body build
Behavioral and environmental
Excessive alcohol use
Cigarette smoking
Low calcium intake
Exercise-induced amenorrhea
High-fiber diet
High-phosphate diet
High-protein diet

Osteoporosis Risk Factors
are found, not on osteoclasts, but
on osteoblasts, osteoblast precursors,
and very early osteoclast precursors.
Parathyroid hormone
causes osteoblasts to (1) stimulate
the release of neutral proteases,
which degrade surface osteoid
and initiate the bone remodeling
cycle; (2) stimulate the release of
unknown factors from osteoblasts,
which stimulate osteoclasts to
resorb bone; and (3) stimulate
osteoblasts to synthesize osteoid
and form bone.
The rate of synthesis and release
of parathyroid hormone by the cell
is related to the extracellular ionized
calcium concentration. Increased
levels of parathyroid
hormone have been noted in the
elderly, possibly because of a
decrease in fractional calcium
absorption in the intestine. These
findings support the conclusion
that the parathyroid hormone–1,25-
dihydroxycholecalciferol axis may
aggravate the progressive loss of
bone mass in the aged.4
Calcitonin is an important calcium-
regulating hormone, the exact
physiologic role of which remains
controversial. It does not regulate
directly the functions of parathyroid
hormone or vitamin D metabolites,
but its ability to modulate serum calcium
and phosphate levels is
significant. Calcitonin is produced
and secreted by the C cells (parafollicular
cells) of the thyroid gland.
The major target tissues for calcitonin
seem to be bone, kidney, and
the gastrointestinal tract. In bone,
the major defined action is the inhibition
of osteoclastic bone resorption.
Estrogens and Corticosteroids
The association between bone
loss, fracture risk, and a postmenopausal
state (naturally occurring
or surgically induced) is well
known. Many studies have shown
that bone loss is accelerated after
menopause; when ovarian hormone
production ceases and circulating
levels fall to 20% of previous levels,
this bone loss can be reversed only
by administration of estrogen.6
Although estrogens are known to
inhibit bone resorption, the mechanisms
responsible for this effect are
not understood. Only recently has
the presence of specific estrogen
receptors in osteoblast-like cells
been confirmed.7 Although the level
of such receptors is very low, the fact
that they appear to be active in
osteoblasts and osteoblast-like cells
provides the first real evidence that
bone is a target tissue for estrogen
action. Preliminary evidence also
suggests that osteoclasts possess
estrogen receptors. If this is true, it is
possible that estrogen may exert
direct control over both bone formation
and resorption.
Both men and women experience
age-related bone loss, particularly
from cortical bone. In women, the
rate of trabecular bone loss increases
in the first few years after menopause,
associated with a decrease in
endogenous estrogens. Not only does
estrogen replacement block this bone
loss in the early postmenopausal
years (years 3 to 6), but a decrease in
fracture rates in the appendicular
skeleton has also been documented.
When used alone, 0.625 mg of conjugated
estrogen per day is the lowest
effective dose for retarding bone loss.
Some studies have suggested that a
lower dose may be effective when
combined with calcium supplementation.
Patients who undergo bilateral
oophorectomy before natural
menopause also respond to estrogen
therapy. To obtain maximal benefit
from estrogen replacement therapy,
it should be started as soon as possible
after surgical or natural menopause.
It is well accepted that any factor
that increases a patient’s exposure to
estrogen (early menarche, late
menopause, estrogen replacement
therapy) can increase the risk of breast
or endometrial cancer. Combined
cyclical estrogen-progestin therapy is
believed to decrease the occurrence of
endometrial, but not breast, cancer. In
patients who have undergone hysterectomy,
unopposed estrogen treatment
(i.e., without the use of a
progestational agent) is indicated.6
The most important factors to consider
in determining whether a patient
should take estrogen is the relative
risk-benefit ratio. In general, patients
who have a strong family history of
breast cancer or endometrial cancer
may be at increased risk of developing
cancer or stroke as a result of estrogen
treatment. Any form of estrogen is
contraindicated in patients with
hypertension or a history of congestive
heart failure, because its effect on
the renin-angiotensin axis increases
sodium retention.6 In addition, the use
of estrogen is known to exacerbate
benign breast diseases and cholecystitis.
Estrogen is strongly beneficial not
only in the prevention of osteoporosis
and hip fractures but also in the prevention
of heart disease in women.
Corticosteroids can cause bone
loss by directly inhibiting calcium
absorption, increasing renal calcium
excretion, and indirectly stimulating
secondary hyperparathyroidism.
Their principal effects are to
decrease production of the intestinal
binding proteins required for calcium
absorption. Very high doses of
steroids decrease both bone formation
and resorption. Even with
doses as low as 10 mg of prednisone
per day, significant bone loss
Thyroid Hormones
Patients with hyperthyroidism
and those who are receiving exogenous
thyroid treatment may develop
osteoporotic bone disease. Both bone
resorption and formation are stimulated,
but resorption seems to occur at
a slightly faster rate than formation.
Patients with hyperthyroidism and
those who take thyroid supplements
for the treatment of a hypothyroid
condition are also at increased risk for
sustaining a hip fracture independent
of bone density. Hence, thyroid hormone
may have an effect on bone
quality as well as bone mass.9
Any patient over the age of 50 who
presents to an orthopaedist with a
hip, distal radial, or vertebral compression
fracture should be evaluated
for the presence of osteoporosis. A
comprehensive medical evaluation
should seek potential causes of secondary
osteoporosis, such as hyperthyroidism,
Cushing’s disease,
disuse, or the use of drugs known to
be associated with osteoporosis (e.g.,
glucocorticoids, thyroid hormone
supplements, phenytoin, immunosuppressants).
The extent of bone loss
and fractures should be assessed, and
baseline biochemical data should be
obtained. A careful history should
include notation of the chronology,
location, type, and severity of back
pain (if back pain is a symptom); previous
treatment; age at onset and
type of menopause (natural or surgical);
family history of osteoporosis;
amount of tobacco or alcohol used;
level of physical activity; and amount
of habitual calcium intake.
Physical examination should
include an accurate measurement of
height and a thorough investigation
to rule out systemic disease. In all
patients, a complete blood cell count,
differential count, and blood chemistry
profile should be performed. Thyroid function should
also be assessed. In patients who are
receiving thyroid hormone supplements,
determination of the thyroidstimulating
hormone level is useful
to be certain that thyroid replacement
is not excessive. Since primary
osteoporosis generally presents with
a normal serum biochemical profile,
abnormalities in any of these studies
suggest that osteoporosis may be secondary
to an underlying disease.
Serum protein electrophoresis
should be performed on all potentially
osteoporotic patients at initial
evaluation. A normal pattern
excludes the presence of multiple
myeloma or a related lymphoproliferative
disorder in 90% of patients.
An analysis of urinary calcium
excretion, normalized for creatinine
(24-hour collection), and the level of
urinary pyridinium cross-links (2-
hour fasting sample) is considered
to be part of the state-of-the-art
approach to diagnosing and managing
an actively resorbing osteoporotic
process. (Pyridinium cross-links are
specific components of the types of
collagens found in bone and cartilage
tissues.) In the case of collagen breakdown,
the measurement of hydroxyproline
excretion has been essentially
replaced by the measurement of pyridinium
cross-links. In addition, since
osteoblastic bone formation follows
osteoclastic resorption, states of high
bone turnover are accompanied by
increased osteoblastic activity as well.
In those instances, analysis of the
serum for osteocalcin, a specific
osteoblast product, is another way to
ascertain bone metabolic activity.
The most characteristic feature of
osteoporosis is decreased radiodensity.
The apparent radiodensity, however,
may vary by up to 30% because
of differences in several factors, such
as film development, patient weight,
and the amount of x-ray exposure. A
lateral radiograph is the best way to
image an osteoporotic spinal deformity.
The usual findings are vertebral
collapse (reduction of anterior and
posterior height), anterior wedging
(reduction in anterior height), and
biconcave compression of the end
plates (“ballooning”), which usually
occurs in the lumbar spinal column.
The nucleus pulposus also may herniate
into the vertebral body
(Schmorl’s node).
Bone Densitometry
The most effective way of screening
for osteoporosis and then following
the results of treatment is by
the measurement of bone density.
Several methods exist for assessing
skeletal density, all of which offer a
dramatic improvement over previously
available methods, such as
standard radiography (Table 4).10
Although measurements of bone
density in different parts of the
skeleton may correlate, it is generally
believed that the direct measurement
of bone density at the
actual site of a fracture is of the
greatest clinical interest.

Complete blood cell count
Sedimentation rate
Blood urea nitrogen
Alkaline phosphatase
Liver enzymes
24-hour urine calcium
Serum protein electrophoresis
Urine pyridinium cross-links
Recommended for further workup
based on initial history
Gastrointestinal malabsorption
Serum carotene
Thyroid function
Plasma cortisol
Serum testosterone (men)
Urine immunoelectrophoresis
Bence Jones protein
Table 3
Laboratory Tests
Single-photon absorptiometry is
a useful method for determining the
amount of bone substance present at
the distal radius, forearm, and calcaneus.
It is relatively inexpensive and
takes only about 15 minutes to perform.
It results in a relatively low
dose of radiation to the patient.
Dual-photon absorptiometry
(DPA) uses transmission scanning
with photons from a radioisotope
source, such as gadolinium 153, that
emits two energy peaks, thus allowing
bone density to be measured
independently from soft-tissue density.
It allows measurement of the
spine, hip, and total body and
requires approximately 20 to 40 minutes
to perform. Systems for performing
DPA are no longer being
manufactured because they have
been replaced by the more accurate
dual-energy x-ray absorptiometry
(DXA) apparatus.
Dual-energy x-ray absorptiometry
is an x-ray-based scanning procedure
that is often used to detect bone
loss in the spine, distal radius, hip, or
total body. This technique is rapid,
taking only 3 to 7 minutes, and delivers
a radiation dose that is so low (1
to 2 mrem) as to be equivalent to
approximately 5% of the radiation
dose of one chest radiograph. Precision
and accuracy estimates for DXA
are excellent. Currently, this may be
the preferred method for assessing
bone loss clinically.
Quantitative computed tomography
(QCT) is a sophisticated procedure
that makes it possible to
measure the trabecular bone compartment
only, thus allowing targeted
analysis of trabecular bone
loss. However, it exposes the patient
to a radiation dose equivalent to that
of several radiographs. This may
make this technique less acceptable
for use in repeated bone-mass measurements.
Radiographic absorptiometry is a
method of noninvasive measurement
of bone mineral from radiographs
of the hands. In this method,
radiographs taken with standard xray
equipment are subjected to computer-
controlled analysis.
Presently, the Health Care Financing
Administration (the federal
agency that administers Medicare)
recognizes only single-photon
absorptiometry and radiographic
absorptiometry as reimbursable
health care costs. This agency is currently
reassessing its coverage policy
for these tests, as well as considering
reimbursement for DPA, DXA, and
QCT. In addition, third-party payers,
such as Blue Cross/Blue Shield, are
reassessing their coverage policies on
bone-mass measurement. Charges for
DPA, DXA, and QCT may be reimbursed
by some insurers, but
orthopaedists should advise their
patients that reimbursement is not
guaranteed. Since the monetary
issues surrounding health care are in
a state of evolution, physicians and
patients must check the local and federal
reimbursement policies to determine
the coverage status of these
relatively expensive tests. The American
Academy of Orthopaedic Surgeons
and the National Osteoporosis
Foundation are working with federal
regulatory agencies, congressional
policy makers, and private insurers to
develop strategies that will make
these tests available to patients who
need them.

Dual-energy x-ray
Quantitative computed
Proximal and distal
radius, calcaneus
Spine, hip, total body
Spine, distal radius,
hip, total body
Technique %
Table 4
Techniques for the Measurement of Bone Mass
Time, min
Dose of
Cost, $
* Precision is the coefficient of variation for repeated measurements over a short period of time in young, healthy
† Accuracy is the coefficient of variation for measurements in a specimen the mineral content of which has been
determined by other means.

Prevention of osteoporosis is of primary
importance, since there are no
safe and effective methods for restoring
healthy bone tissue and normal
bone architecture once they have been
lost. Preventive approaches include
ensuring maximal accumulation of
bone during skeletal growth and maturation
and reducing or eliminating
bone loss after the skeleton matures.
In addition, good nutrition, modifications
of lifestyle (e.g., moderation
in use of alcohol and cessation of cigarette
smoking), and regular physical
activity are important adjuncts to any
prevention and treatment program.
Because most orthopaedists are
exposed to a cross section of patients
with respect to age, playing a proactive
role in osteoporosis prevention is
Adolescence and Young
Adequate calcium nutrition during
growth and maturation are key
determinants of adult bone mass.
Weight-bearing exercise, such as
walking, jogging, and dancing, for 3
to 4 hours per week is also recommended.
Skeletal integrity may be
jeopardized by entities associated
with premenopausal estrogen
deficiency, such as anorexia, bulimia,
excessive athleticism, prolactinoma,
and hyperthyroidism, and by taking
drugs that impair skeletal metabolism,
such as glucocorticoids and
antiepileptic agents. It is important
for the orthopaedist to recognize
these risks and to initiate preventive
measures where possible.
Perimenopause and
Prevention of bone loss in the
postmenopausal period is of the
utmost importance for women at risk
for osteoporosis. A strong family history
of osteoporosis or a medical and
social history that suggests an
increased risk of osteoporosis (Table
2) should lead to the performance of
a bone-density examination. If low
bone mass is detected, a high calcium
intake alone will not significantly
mitigate the accelerated spinal loss of
the postmenopausal period. Estrogen
is the therapy of choice. While
the best exercise regimen to promote
skeletal health has not yet been determined,
evidence indicates that
weight-bearing exercise can reduce
bone loss in this group. Preliminary
studies suggest that injectable calcitonin
is effective in reducing postmenopausal
bone loss; however, it
has not been approved by the Food
and Drug Administration (FDA) for
this indication.
Advancing Age
Patients who do not experience
rapid bone loss at menopause but
present with moderate to severe
osteoporosis beginning in the seventh
decade of life (type II osteoporosis)
can still benefit from
prophylactic measures. Appropriate
calcium, vitamin D, and exercise are
necessary, and cigarette smoking
and excessive alcohol intake should
be avoided.
The treatment of patients who have
sustained osteoporotic fractures
includes maintaining their quality
of life, encouraging mobilization,
controlling pain safely, and promoting
social interaction. Prolonged
bed rest, inadequate
attention to nutrition, and social
isolation are avoidable pitfalls.
Drugs that impair motor function,
such as sedatives, tranquilizers,
and hypnotic agents, should be
avoided, since they may predispose
to falls and fractures.
For the patient who has low bone
mass or a typical osteoporotic fracture,
a complete history and physical
examination are necessary, and
a thorough laboratory workup
should be ordered to exclude common
medical disorders known to
cause bone loss. Osteomalacia,
which can masquerade as osteoporosis,
must be excluded. Treatment
mainstays include adequate
calcium intake, mild weight-bearing
exercise, and the use of calcitonin,
etidronate (Didronel), or
estrogen in selected patients. The
indications for bone biopsy are few
and are limited to those situations
in which histologic examination of
bone is the only means by which
osteomalacia, hyperparathyroidism,
or neoplasia can be excluded
with certainty. The routine use of
bone biopsy in patients with osteoporosis
is not recommended except
when patients are being followed
up as part of an experimental protocol.
Adequate calcium in the diet is
required during growth because
the body does not make calcium. It
continues to be an essential nutrient
after full skeletal growth has
been achieved because the body
loses calcium every day through
Table 5
Indications for Bone-Mass
In estrogen-deficient women, to
make decisions about estrogen
replacement therapy
In patients with spinal osteopenia, to
diagnose osteoporosis and make
decisions about further workup
and treatment
In patients on long-term steroid
treatment, to diagnose decreased
bone mass in order to adjust dose
In patients with asymptomatic
primary hyperparathyroidism, to
identify need for surgical
shedding of skin, nails, and hair,
as well as in sweat, urine, and
feces. When the diet does not contain
enough calcium to offset these
losses, bone is catabolized in order
to scavenge calcium. The current
recommended dietary allowance
in the United States is 1,200
mg/day in adolescence through
age 24 and 800 mg/day for older
adults. It is recommended that
men and premenopausal women
ingest 1,000 mg/day and that
postmenopausal women not
receiving estrogen ingest 1,500
mg/day. As already mentioned,
high calcium intake will not protect
a woman against bone loss
caused by estrogen deficiency
(type I osteoporosis), physical
inactivity, alcohol abuse, smoking,
or various medical disorders
and treatments.11,12
Calcitonin has been repeatedly
shown to decrease osteoclast activity.
It may also have an analgesic
effect; the mechanism causing this
pain relief is unclear. Calcitonin is
inherently safe. It is available in the
United States only as an intramuscular
or a subcutaneous injection.
Use of the injectable form may be
associated with nausea, vomiting, a
flushing sensation over the face,
and irritation at the injection site.
Injectable salmon calcitonin is
approved by the FDA for treating
established osteoporosis at a
dosage of 100 IU daily. Lower
dosages are, however, commonly
utilized in practice. Human calcitonin
is not FDA approved for the
treatment of osteoporosis, but it is
approved for the treatment of
Paget’s disease. A nasal spray form
of calcitonin is under investigation.
Patients should be advised that the
cost of calcitonin treatment is high,
averaging approximately $120 per
Estrogens and Hormone
Loss of estrogen production at
any age results in increased bone
remodeling, which is associated
with loss of bone tissue. In patients
with an intact uterus, estrogen can
increase the risk of endometrial
cancer unless either intermittent or
continuous progestin therapy is
given to prevent this complication.
Estrogen replacement therapy
returns bone remodeling to the
level seen in premenopausal
women, prevents bone loss, and
reduces fracture risk. Estrogen
replacement therapy, if recommended
by an orthopaedist, should
be used in conjunction with the
consultation of an obstetriciangynecologist
or endocrinologist.
Patients should be monitored for
uterine response and followed
yearly with mammography. There
may be a small increase in the risk
of breast cancer, particularly with
long-term use (more than 10 years)
and high doses.13
The bisphosphonates, originally
called diphosphonates, are a group
of synthesized chemical compounds
with structures similar to that of
pyrophosphate. This property renders
them chemically attractive to
bone mineral surfaces. Once bound
to bone mineral, bisphosphonates
inhibit bone resorption. A number of
bisphosphonates are involved in
ongoing research protocols.
Published double-blind controlled
studies utilizing the bisphosphonate
etidronate, given 2 weeks of
every 3-month period, demonstrated
increased spinal bone mass
and a possible decrease in the number
of spinal fractures.14 However,
etidronate, if administered continuously,
will cause a mineralization
defect with an adverse effect on
bone. Orthopaedists who prescribe
this drug should advise patients that
it is experimental and not FDA
approved for the treatment of osteoporosis.
If this experimental form of
therapy is chosen, etidronate should
be administered in a dose of 400
mg/day and should be taken on an
empty stomach with a glass of water
only. Food should not be ingested
for at least an hour, because of the
poor absorbability of bisphosphonates
from the gastrointestinal tract.
It is important to administer this
drug in a noncontinuous cyclical
pattern (e.g., 2 weeks on, 10 to 13
weeks off, 2 weeks on, and so on) to
avoid the mineralization defect associated
with continuous use. Longterm
studies are required to
determine the ultimate utility of this
cyclical therapy.
Although fluoride has been used
for approximately 30 years, it
remains an experimental drug for
the treatment of osteoporosis.
Recent data suggest that fluoride
may increase spinal bone mass but
without a reduction in vertebral
fracture rate. Of greater concern is
the fact that an increased incidence
of appendicular fractures may occur
in certain patients. The fracture incidence
may be due to the toxicity of
sodium fluoride in the dosage
used.15 At present, there are no data
to determine whether lower doses
will be safe and effective. Until such
data are available, fluoride administration
should be considered highly
experimental. On the basis of published
reports and a careful prospective
analysis of a cohort of patients,
the senior author (T.A.E.) has discontinued
using this drug.
Vitamin D
Most multivitamin supplements
contain 400 IU of vitamin D, and
milk contains 100 IU per cup. It
seems reasonable for elderly persons
to take a multivitamin with 400
IU of vitamin D. More than 800 IU of

vitamin D per day is not recommended
because of its potential toxic
side effects. Although an increase in
bone mineral content has been
reported in patients receiving active
forms of vitamin D, it is still considered
experimental in the treatment
or prevention of osteoporosis.16
Evolving Therapies
Several drugs are currently in clinical
trials to test their safety and efficacy
in the treatment of osteoporosis. These
include a variety of new bisphosphonates,
nasal spray calcitonin, and
active 1,25-dihydroxycholecalciferol.
In the future, growth factors and other
recombinant peptides may be shown
to be safe and effective in restoring
bone mass. Exercise remains a potentially
important form of therapy that
has been insufficiently studied. It is
conceivable that the appropriate type,
intensity, and frequency of exercise
therapy will be found effective in preventing
bone loss and increasing bone
mass. Biophysical modalities such as
electromagnetic stimulation and ultrasound
are currently under study.
While none of these is recommended
for use at this time, the orthopaedist
should remain aware of these investigations,
since patients frequently ask
their doctors about emerging technologies
that may benefit them.
Back pain is frequently reported
by patients with spinal osteoporosis.
In many cases, the symptoms are
produced by compression fractures
in the thoracic and lumbar spine.
Microfractures can also occur in trabeculae
even when the vertebrae
appear architecturally normal.
Regardless of whether a macrofracture
or a microfracture exists, muscle
spasm is often the major cause of the
patient’s symptoms. To address
these problems, a comprehensive
spinal rehabilitation program
should be developed.
In terms of prevention, patients
should be instructed in the proper
techniques of posture and body
mechanics. They should avoid lifting
heavy objects and should learn
proper bending motions.17 The use
of a cane often provides the patient
with better balance and reduces the
possibility of falls. Patients should
also be instructed in pectoral stretching,
deep breathing, and back extension
exercises.17 Swimming and
bicycling are excellent means of
maintaining aerobic fitness and do
not place undue stresses on the vertebral
Management of acute and chronic
pain can be more difficult. Extended
bed rest is not recommended in a
comprehensive treatment program
for osteoporotic patients. A properly
fitted back support is occasionally
appreciated, although these braces
should be discarded as soon as
symptoms improve. Management
of chronic pain secondary to microfractures
and kyphotic or scoliotic
changes in the spine requires a program
of back extension exercises and
specific physical therapy tailored to
the patient’s needs.
Osteoporotic Fractures
The treatment of fractures in
patients who have osteoporosis
requires special care and attention
because of the special problems
associated with bone with deficient
mechanical properties and fractures
that are excessively comminuted.
Fracture healing does not seem to be
impaired in elderly persons or in
patients with idiopathic osteoporosis.
Hence, once an acceptable reduction
and an appropriate degree of
stabilization of the fragments have
been achieved, fracture healing
should progress normally.
Fractures to the spinal column in
osteoporotic patients generally
occur within the bodies of the vertebrae
and usually do not affect the
posterior elements. Thus, the vast
majority of these fractures are stable
and rarely require surgical stabilization.
The temporary use of a lowprofile
corset or polypropylene
brace may reduce muscle spasm and
symptoms. The orthosis should be
constructed so that it does not compromise
chest expansion and pulmonary
function. In most cases,
patients do not require a brace in
order to become comfortable.
In rare cases, unstable fractures do
occur in the osteoporotic skeleton,
and these may require surgical intervention
(e.g., when there is neurologic
compromise). The major problem in
treating these unstable fractures is
gaining adequate purchase for
implants in osteoporotic bone.
The majority of fractures of the long
bones in elderly osteoporotic patients
are best managed by early surgical stabilization.
Surgery should be kept
simple to minimize operative time,
blood loss, and physiologic stress. The
goal of operative intervention is to
achieve early weight-bearing status
for the lower extremity and rapid
restoration of functional capacity in
the upper extremity.
Fracture-fixation devices that
allow compaction of fracture fragments
into stable patterns, minimize
stresses at bone-implant interfaces,
and reduce stress shielding are preferred.
Because of the inability of the
skeleton to hold plates and screws
securely, sliding nail-plate devices,
intramedullary rods, and tensionband
wire constructs that share loads
between implants and bone are preferred.
Methylmethacrylate can be
used to enhance the stability of screws
in plate-fixation systems if necessary.
Several manufacturers are attempting
to develop new and improved fracture
grout materials that not only will
serve to stabilize orthopaedic
implants but also may be osteoconductive
and potentially resorbable.
Prolonged immobilization associated
with “conservative fracture management”
places the patient at risk for
56 Journal of the American Academy of Orthopaedic Surgeons
medical complications. Pneumonia,
congestive heart failure, thromboembolic
disease, decubitus ulceration,
and further generalized musculoskeletal
deterioration are frequent
complications in bedridden elderly
patients. In addition, the delicate,
poor-quality skin of many elderly
patients is prone to sloughing, particularly
when there is a peripheral neuropathy
or vascular disease. This can
lead to serious complications when
casts are applied, particularly to the
lower extremities. In these instances,
particular attention should be paid,
with well-padded casts being used.
One of the problems commonly
associated with osteoporosis is the
occurrence of stress fractures leading
to pain, angular deformity, and, in
many cases, complete fractures of the
vertebrae or long bones. Although
the question of stress fractures is
beyond the scope of this report, it is
important for the orthopaedist to recognize
that osteoporotic patients
who describe pain at specific skeletal
sites may be experiencing a stress
fracture even when the radiographs
appear normal. A bone scan, CT
scan, or MR imaging study may be
required to make the definitive diagnosis.
When stress fractures occur in
parts of the skeleton that experience
significant loads, prophylactic internal
fixation may be required to avoid
a catastrophic event, such as a displaced
femoral neck fracture.
Unless the orthopaedist is subspecialized
in an area of musculoskeletal
medicine that deals strictly with
young patients, it is likely that osteoporosis
will become part of the dayto-
day clinical experience. A
comprehensive working knowledge
of diagnostic modalities, medical
therapeutics, and the special needs of
the osteoporotic surgical patient will
become more important as the population
continues to age. Despite our
best efforts at large-scale osteoporosis
prevention, one can anticipate
that the consequences of osteoporosis
will affect orthopaedic surgical
practice well into the 21st century.
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