Minggu, 26 Oktober 2008

Osteoporosis

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
Osteoporosis
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,
25-hydroxycholecalciferol
(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
messengers.3
Parathyroid Hormone
Parathyroid hormone and vitamin
D together form a parathyroid hormone–
1,25-dihydroxycholecalciferol
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
intertrochanteric)
Factors related to menopause
Trabecular and cortical
Vertebrae (multiple wedged),
hip (mainly femoral neck)
Factors related to aging
51–75
6:1
>70
2:1
Type I
Feature (Postmenopausal)
Table 1
Types of Involutional Osteoporosis
Type II
(Age-Associated)
Genetic and biologic
Family history
Fair skin and hair
Northern European background
Scoliosis
Osteogenesis imperfecta
Early menopause
Slender body build
Behavioral and environmental
Excessive alcohol use
Cigarette smoking
Inactivity
Malnutrition
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
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.
5
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.
6
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
occurs.
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
Diagnosis
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.
Radiography
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.

Routine
Complete blood cell count
Sedimentation rate
Electrolytes
Creatinine
Blood urea nitrogen
Calcium
Phosphorus
Protein
Albumin
Alkaline phosphatase
Liver enzymes
24-hour urine calcium
Serum protein electrophoresis
Special
25-Hydroxycholecalciferol
1,25-Dihydroxycholecalciferol
Osteocalcin
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.

Osteoporosis
Single-photon
absorptiometry
Dual-photon
absorptiometry
Dual-energy x-ray
absorptiometry
Quantitative computed
tomography
Radiographic
absorptiometry
Proximal and distal
radius, calcaneus
Spine, hip, total body
Spine, distal radius,
hip, total body
Spine
Phalanges
1-3
2-4
0.5-2.0
2-5
1-2
Precision,*
Technique %
Table 4
Techniques for the Measurement of Bone Mass
Site
5
4-10
3-5
5-20
4
Accuracy,†
%
15
20-40
3-7
10-15
2
Examination
Time, min
10-20
5
1-3
100-1,000
100
Dose of
Radiation,
mrem
75-100
150-200
150-200
150-200
75-100
Approximate
Cost, $
* Precision is the coefficient of variation for repeated measurements over a short period of time in young, healthy
persons.
† Accuracy is the coefficient of variation for measurements in a specimen the mineral content of which has been
determined by other means.

Prevention
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
possible.
Adolescence and Young
Adulthood
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
Postmenopause
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.
Treatment
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.
Calcium
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
Measurement
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
parathyroidectomy
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
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
month.
Estrogens and Hormone
Replacement
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
Bisphosphonates
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.
Fluoride
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.
Rehabilitation
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
column.
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
Osteoporosis
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.
Conclusion
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.
References
1. Riggs BL, Melton LJ III: The prevention
and treatment of osteoporosis. N Engl J
Med 1992;327:620-627.
2. Riggs BL, Melton LJ III: Evidence for
two distinct syndromes of involutional
osteoporosis. Am J Med 1983;75:899-901.
3. Eastell R, Riggs BL: Calcium homeostasis
and osteoporosis. Endocrinol Metab
Clin North Am 1987;16(4):829-842.
4. Silverberg SJ, Shane E, de la Cruz L, et
al: Abnormalities in parathyroid hormone
secretion and 1,25-dihydroxyvitamin
D3 formation in women with
osteoporosis. N Engl J Med 1989;320:
277-281.
5. Hurley DL, Tiegs RD, Wahner HW, et
al: Axial and appendicular bone mineral
density in patients with long-term
deficiency or excess of calcitonin. N Engl
J Med 1987;317:537-541.
6. Barzel US: Estrogens in the prevention and
treatment of postmenopausal osteoporosis:
A review. Am J Med 1988;85:847-850.
7. Eriksen EF, Colvard DS, Berg NJ, et al:
Evidence of estrogen receptors in normal
human osteoblast-like cells. Science
1988;241:84-86.
8. Baylink DJ: Glucocorticoid-induced
osteoporosis. N Engl J Med 1983;309:
306-308.
9. Bauer DC, Cummings SR, Tao JL, et al:
Hyperthyroidism increases the risk of
hip fractures: A prospective study. J
Bone Miner Res 1992;7:S121.
10. Johnston CC Jr, Slemenda CW, Melton
LJ III: Clinical use of bone densitometry.
N Engl J Med 1991;324:1105-1109.
11. Prince RL, Smith M, Dick IM, et al: Prevention
of postmenopausal osteoporosis:
A comparative study of exercise,
calcium supplementation, and hormone-
replacement therapy. N Engl J
Med 1991;325:1189-1195.
12. Riis B, Thomsen K, Christiansen C:
Does calcium supplementation prevent
postmenopausal bone loss? A doubleblind,
controlled study. N Engl J Med
1987;316:173-177.
13. Steinberg KK, Thacker SB, Smith SJ, et
al: A meta-analysis of the effect of estrogen
replacement therapy on the risk of
breast cancer. JAMA 1991;265:1985-
1990.
14. Riggs BL: A new option for treating
osteoporosis. N Engl J Med 1990;323:
124-125.
15. Riggs BL, Hodgson SF, O’Fallon WM, et
al: Effect of fluoride treatment on the
fracture rate in postmenopausal women
with osteoporosis. N Engl J Med
1990;322:802-809.
16. Tilyard MW, Spears GFS, Thomson J, et
al: Treatment of postmenopausal osteoporosis
with calcitriol or calcium. N Engl
J Med 1992;326:357-362.
17. Sinaki M: Postmenopausal spinal osteoporosis:
Physical therapy and rehabilitation
principles. Mayo Clin Proc
1982;57:699-703.
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