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Lynn
Hickey, MD
The
purpose of this review is to present current information
necessary in the evaluation and treatment of osteoporosis.
The focus will be tailored to postmenopausal women, as they
are the largest subset of the population at risk for osteoporosis.
It is estimated that ten million people in our country have
osteoporosis, with eighty percent of them being women. Another
eighteen million qualify as having osteopenia. These numbers
will rise as the population ages, but patients can be taught
about steps they can take toward preventing osteoporosis
when they are young.
Osteoporosis
is defined as a "disease characterized by low bone
mass and micro architectural deterioration of bone tissue
leading to enhanced bone fragility and a consequent increase
in fracture incidence" (Kenny, 2000). There are over
250,000 hip fractures per year in women, and over 500,000
vertebral fractures. The greatest probability of hip fracture
over age 50 is in Caucasian women at 14%, followed by Caucasian
men, African American women, and lastly African American
men at 3%. There is a 25% increase in mortality the year
following a fracture, and only another 25% will regain their
pre-fracture functional status.
Bone
mass in women increases from puberty to the mid 20's and
30's until a maximum is reached. It remains stable initially,
but then begins a slow decline until the perimenopausal
period where the rate of loss can then be 3-7% per year
for up to ten years. Afterward, the rate of loss slows again
to 1-2% per year. It is felt that increasing age and decreasing
estrogen levels lead to an increase in osteoclast activity
with increased bone resorption and decreased osteoblast
capacity. The net result is that of bone loss. Contributing
to increased bone resorption are decreased calcium and vitamin
D levels in the elderly, which causes an increase in parathyroid
hormone production. The treatment goal of osteoporosis is
to minimize this bone loss and build new bone tissue, thus
decreasing the chance of new or recurrent fracture.
The
National Osteoporosis Foundation has delineated risk factors
for osteoporosis that can be used to guide screening and
treatment. This list includes both modifiable and nonmodifiable
factors. Nonmodifiable risk factors include female sex,
increasing age, Caucasian race, history of fracture as an
adult, history of fracture in a primary relative, dementia,
and poor health or frailty. Modifiable risk factors include
smoking, alcoholism, body weight below 127 pounds, estrogen
deficiency (including amenorrhea and early menopause), recurrent
falls, poor lifelong calcium intake, and poor vision despite
correction. Drugs and comorbid medical conditions can also
add to the risk of osteoporosis. Examples include prolonged
corticosteroid use, primary hyperparathyroidism, hyperthyroidism
or excessive synthroid use, multiple myeloma, Paget's disease,
and malabsorptive diseases such as cystic fibrosis, celiac
sprue, and inflammatory bowel disease.
The
determination of bone mineral density is an objective measurement
of osteopenia or osteoporosis with respect to a healthy
young woman's "normal" value. This is done by
dual energy x-ray absorptiometry or DEXA. Bone mineral density
from the hip is most accurate for predicting risk of fracture,
and that of the lumbar spine is best for monitoring treatment.
The World Health Organization has defined acceptable bone
mineral density as falling within one standard deviation
of the "normal" value, or a T score above -1.
Osteopenia is defined as a value falling between 1 and 2.5
standard deviations, or a T score from -1 to -2.5. Osteoporosis
is defined as bone mineral density less than 2.5 standard
deviations from the "normal" value, or a T score
of below -2.5. The National Osteoporosis Foundation has
recommended treatment of osteoporosis for T scores below
-2, and treatment of osteopenia for T scores below -1.5
with any risk factors present.
Prevention
and treatment of osteopenia and osteoporosis is multi-faceted,
and can be initiated non-pharmacologically in all patients.
Women (including adolescents) should be educated about osteoporosis
during office visits, with emphasis on eliciting risk factors
from their history. Smoking cessation, minimal alcohol
intake, weight bearing exercise, and the importance of adequate
calcium and vitamin D intake is always worth stressing.
The NIH consensus statement on osteoporosis emphasizes that
"the bone mass attained early in life is perhaps the
most important determinant of life-long skeletal health."
The greater the peak bone mass attained, the greater protective
advantage provided. Female athletes are often at risk given
the triad of eating disorder, osteoporosis, and amenorrhea.
Maintaining good nutrition and getting regular exercise
can also be applied to the elderly and nursing home patients
to help decrease the risk of falls and fractures.
Currently
bone mineral density testing is performed based on age and
risk factors. The National Osteoporosis Foundation
suggests that all women over age 65 have a bone density
test, as well as women below age 65 that have risk factors.
Treatment is started based on the T scores previously mentioned.
Calcium intake should be increased to 1500mg per day, and
vitamin D intake should fall between 400-800 I.U. per day.
A non-dietary supplement is usually needed as it is difficult
to obtain these amounts by diet alone on a daily basis.
Calcium citrate is more easily absorbed than calcium carbonate
because it is a more soluble form. Bedtime administration
has the greatest effect on bone resorption.
Several
classes of drugs have been approved for treatment and prevention
of osteoporosis in addition to extra calcium and vitamin
D. The goal of these drugs is to decrease bone resorption.
Estrogen replacement therapy for at least 5 years in the
postmenopausal period has been shown to decrease the incidence
of fracture; 30-70% for hip and 50% for vertebral fractures.
Bone density losses in the hip and spine can also be prevented
when treatment is started within 5-10 years of menopause.
An increase in bone density is also seen when treatment
is started in older women (ages 70 and above). Estrogen
can be given in either a cyclical or continuous manner.
It is important to note that the benefit decreases when
treatment is stopped. The debate over long term estrogen
replacement and the adverse effects of estrogen are beyond
the scope of this review.
Bisphosphonates
such as alendronate and risendronate have a net effect on
osteoclast activity by increasing cell death. They are approved
for both treatment and prevention of osteoporosis. Studies
have shown a 48% decrease in hip and vertebral fractures
with bisphosphonates when compared to placebo. Bisphosphonates
also increase bone density in the hip and spine. The optimal
treatment duration is not known. The preventive dose for
alendronate is half that of the treatment dose. Major
side effects are gastrointestinal in origin, with esophagitis
being the main complication in those who do not take the
drug correctly.
Another
class of drugs used to treat osteoporosis is the selective
estrogen receptor antagonists, such as raloxifene. These
drugs act as estrogen agonists on the bone and heart, but
are antagonists at the breast and uterus. They may be considered
for patients unable to take estrogen replacement therapy.
Raloxifene has been studied in the prevention of osteoporosis,
and has shown an increase in bone mineral density by 2.5%
at multiple sites.
Calcitonin
hormone is made by the C cells of the thyroid to promote
the uptake of calcium to the bones from the blood and inhibit
bone resorption. It is administered by nasal spray at doses
of 200 I.U. per day. Calcitonin has been shown to increase
bone density in the spine and decrease the incidence of
vertebral fractures by 40% in older women when compared
to placebo. It has not been effective in preventing bone
density loss in early postmenopausal women, or in increasing
bone density at the hip.
In
summary, awareness of osteoporosis should be raised whenever
possible, especially in female patients nearing or beyond
the menopausal period. Combining analysis of age, risk factors,
and bone mineral density testing with simple lifestyle modifications
can help to preserve a good quality of life. Calcium is
essential throughout the life span, and pharmacological
treatment should be provided when necessary.
REFERENCES
- Osteoporosis
Prevention, Diagnosis, and Therapy. NIH Consensus
Statement online. 2000 March 27-29; 17(1):
1-36.
- Eastell
MD, R. Treatment of Postmenopausal Osteoporosis.
New England Journal of Medicine. 1998; 338(11):
736-746.
- Heinemann
MD, D.F. Osteoporosis: An overview of the National
Osteoporosis Foundation clinical practice guide.
Geriatrics. 2000; 55(5): 31-36.
- Kenny
MD, A.M. Osteoporosis: Pathogenesis, Diagnosis,
and Treatment in Older Adults. Rheumatic Disease Clinics
of North America. 2000; 26(3): 569-585.
- Manson
MD, J.E. Postmenopausal Hormone Replacement
Therapy. New England Journal of Medicine.
2001; 345(1): 34-40.
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