Course Authors
Susan C. Stewart, M.D.
Dr. Stewart reports no commercial conflict of interest.
Estimated course time: 1 hour(s).
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With what we know today, there is really no reason why the rising generation of young women should suffer the deformities and fractures of osteoporosis when they reach old age. It used to be thought that the all too common vertebral, hip, and wrist fractures were the inevitable consequences of aging. That is simply not true. Proper diet, exercise, and a number of new medications can be used for both prevention and treatment of primary osteoporosis. By "primary," I mean there are no other detectable causes, i.e., medication (steroids, anticonvulsants), endocrine condition (hyperthyroidism or hyperparathyroidism), or bone disease causing the bone loss.
For this presentation I interviewed Dr. Doris Bartuska, Professor of Medicine and Director of Endocrinology, Diabetes, and Metabolism Clinical Services, Medical College of Pennsylvania and Hahnemann University. With Dr. Bartuska's expert help, I will approach this topic by answering three questions:
- How do you prevent primary osteoporosis?
- How do you detect primary osteoporosis?
- How do you treat primary osteoporosis?
Prevention: Target Young Women
For this effort we would like to appeal to all pediatricians, all adolescent specialists, all internists and gynecologists treating younger patients. In every woman, active bone formation occurs up to the age of 30, when she achieves peak bone mass. After that there is a gradual loss of bone until menopause, when there is an acceleration of bone loss for a period of about five years. Following that, there is again a gradual steady loss of bone. A woman who achieves a high peak bone density is much less likely to fall below the critical bone density at which fracture risk increases significantly as she ages.
Young women must be educated and encouraged to adopt eating and exercise habits that contribute to bone formation. One half to one hour of weight bearing exercise 3-6 days per week combined with adequate calcium intake, 1000-1500mg/day, and vitamin D 400-800 IU/day are the most important building blocks of bone.
Two trends in modern life that are great hazards to bone formation are the sedentary life style and phosphoric acid-containing soda drinks. These drinks have a low pH and require buffering within the body and utilize skeletal calcium carbonate. Frequently girls and young women trade in their milk for diet sodas, depriving themselves of the single most important source of calcium, milk, and adding to their diet compounds that decrease bone mass. An 8 oz. glass of milk, 8 oz. of yogurt, a 1.5 oz. serving of cheese all provide 300 or more milligrams of calcium, providing a big boost to the daily requirement.
The sedentary life-style can occur in front of a TV screen or a computer terminal. It is still sedentary. Conversely, too much exercise can backfire and interrupt build-up and cause loss of bone mass. Exercises that are associated with extreme thinness -- distance running, gymnastics and ballet dancing can lead to abnormally low estrogen levels with cessation of menstrual periods. This mimics the post-menopausal state with its accompanying bone loss. Physicians should also always be on the alert for the eating disorder, anorexia nervosa, which contributes to bone loss by the same mechanism.
Detection: Target Middle-Aged Women
Most radiologists agree that if a plain film reveals osteoporosis, there has been a 30-50% decrease in bone mass from the expected norm. Plain films are certainly not appropriate for screening for osteoporosis, since they reveal late-stage disease. The current gold standard test is the "DEXA," Dual Energy X-ray Absorptiometry. This technique is becoming widely available in this country. The standard test provides a density measurement of the lumbar spine and the femur.
These measurements are compared with a standardized measurement of a healthy 35-year-old woman, and expressed as a percentage of that number. They are also plotted on a nomogram (below) of bone mass densities (BMD) at various ages and expressed as standard deviations from the expected density.
"Osteopenia" is defined as bone mineral density up to 2.0 standard deviations below the norm (the orange area) and osteoporosis as a deviation greater than 2.0 below the norm. The blue area represents BMD values greater than average. Women whose BMD's fall below the fracture threshold (the dotted line), can be expected to suffer more orthopedic problems. These procedures cost in the $100-300 range and are generally not covered by insurance without a specific medical indication.
Another group of tests useful in osteoporosis are the bone resorption assays, either in urine or blood, which measure markers of resorption. Pyrilinodine and pyrilinodine peptides quantitatively reflect the breakdown of bone. Most authorities agree that this is a rapidly evolving field and that the choice of a test depends on what is available at the local laboratory. Since these tests measure a dynamic process, they are most useful in monitoring treatment, particularly when antiresorptive therapy is being used.
Many asymptomatic women would benefit from testing and treatment to stabilize and even reverse bone loss, particularly in the immediate postmenopausal period. A number of risk factors have been shown to increase the likelihood that a woman will get osteoporosis.
Risk Factors in Primary Osteoporosis
- Family history
- Caucasian or Asian race
- Sedentary life
- Cigarette smoking
- Excessive alcohol
- Early menopause or hysterectomy
- High coffee intake
- Poor diet: anorexia, lactose intolerant
These risk factors are additive. The presence of a number of them should influence the decision to go ahead and do a bone density.
Considering Secondary Osteoporosis
Once the test has been applied and osteopenia or osteoporosis has been detected, it is very important to rule out other correctable causes of osteoporosis. A serum calcium, phosphate, alkaline phosphatase, T4 and TSH (highly sensitive) will be helpful in looking for hyperthyroidism, too much thyroid replacement, hyperparathyroidism, or osteomalacia. A detailed medication history should be taken. Corticosteroids, anticonvulsants, loop diuretics, thyroid replacement hormone are the major culprits.
Treatment: Target Older and Middle-Aged Women
There are two major scenarios for treatment of primary osteoporosis. One is stabilizing and preventing bone loss in middle-aged women at risk for osteoporosis. The other is treating, usually older women, who are developing fractures. Treatment modalities are increasing. Alendronate (Fosamax) and the intranasal form of calcitonin (Miacalcin) have recently become available. Other medications are in the pipeline or nearing approval, like the new class of compounds, "SERMs," Specific Estrogen Receptor Modifier drugs, like raloxifene, as well as the slow-release fluoride.
Calcium and Vitamin D
These two building blocks underlie every form of treatment. The American population consumes a notoriously low calcium diet, estimated at no more than 400-600mg/day for most adults. The recommended daily intake for mature, menstruating women is 1000mg/day and for postmenopausal or oophorectomized women, 1500mg/day, the equivalent of 3-5 servings of dairy product per day. This intake may not be feasible for most women, and calcium supplementation is advised. Calcium carbonate supplements contain the highest amount of available calcium, but may not be tolerated by women who are prone to constipation. Alternatives are calcium citrate and phosphate. It is important to calculate the amount of elemental calcium available from these supplements, since that is the form of calcium recommended.
Vitamin D intake is generally not a problem in a diet adequate in dairy products. For those not ingesting dairy products, 400-800 IU, the amount in one or two standard multivitamins, is the correct amount. Inadequate exposure to sunlight, which converts the provitamin to the active compound, may be a problem for some elderly women who are shut-ins.
Estrogens and Hormone Replacement Therapy (HRT)
The critical 0.625mg/day level of conjugated estrogens (or estradiol equivalent) has been shown to stabilize and substantially reduce the rate of postmenopausal bone loss. For a woman who is perimenopausal, a bone density measurement may help to make the decision about taking hormone replacement therapy. If bone mass density is low, HRT will address the issue of preserving bone as well as other perimenopausal medical problems. Women who have an intact uterus should take cyclical or combination therapy with progesterone. A history of thrombophlebitis or previous breast cancer are considered contraindications to HRT by most physicians. Tamoxifen, the anti-estrogen used in the treatment of breast cancer, has been found to have a beneficial effect on bone, like estrogen. Many postmenopausal omen with breast cancer are on this compound.
Despite the benefits of estrogen, many women are reluctant to take it for fear they may develop breast cancer. Whether this concern is entirely justified cannot be answered at this time by existing studies, which have yielded iffering results. Another problem with HRT is uterine bleeding, which can be quite heavy with cyclical therapy and unpredictable with combination therapy. A high proportion, in some studies 40%, of women who started HRT discontinue it, often without follow-up or continuing therapy with another regimen.
The problems with estrogenic compounds that are active on breast and uterine tissue may be addressed by SERMS, an estrogen analogue that reduces bone resorption, but has no effect on breast and endometrial tissue. These compounds may be the ideal answer to prevention in postmenopausal women, particularly if they also have effects beneficial to the cardiovascular system.
Calcitonin
Preparations of this hormone, with a primary effect of halting bone resorption, have been available for a number of years in a subcutaneous or intramuscular injected form. Now an intranasal preparation of calcitonin (Miacalcin) has been released. One spray into a single nostril daily, alternating sides, provides a 200mcg dose, which when absorbed is as effective as the 100mcg subcutaneous dose. One remarkable thing about calcitonin is that it has an analgesic effect on fractured bone, especially on painful vertebral fractures. Because of calcitonin's strong antiresorptive effect that results in increased bone formation, adequate vitamin D (400-800IU) and calcium (1000mg) must be taken daily with this drug. The main side effect, not surprisingly, is nasal irritation and dryness. There is some concern about adequacy of absorption in the presence of an upper respiratory infection.
Biophosphonates
Alendronate (Fosamax) is the newly released bisphosphonate. At a 10mg daily dose, it also works by decreasing bone resorption, and can be used as an alternative in women unable to take estrogen. Alendronate's absorption characteristics make it somewhat awkward to take, but once these are mastered, this compound has been shown to be very effective. Alendronate is very poorly absorbed; it must be taken on an empty stomach that will remain empty for at least 1/2 hour, usually first thing in the morning. Maintaining an upright posture at this time is also recommended because of the development of lower esophageal erosions in some cases. Adequate calcium (1000-1500mg) and vitamin D (400-800IU) must also be taken daily to support the net bone build-up.
Sodium Fluoride
A new slow-release form of sodium fluoride is under consideration and may be available soon. This form of fluoride sidesteps the problems of previously used fluoride compounds by delivering lower amounts of fluoride to the blood stream and the bone, and does not result in the fragile bone that occurred with plain sodium fluoride. In contrast to the anti-resorptive drugs just described, fluoride works by stimulating bone formation, so supplementation of 800mg of calcium per day (in addition to dietary calcium) and the 400-800IU of Vitamin D are mandatory. Otherwise bone resorption may occur to meet the demand for bone formation.
Summary
We urge you to build prevention of primary osteoporosis in younger patients into your practice; to work to evaluate for risk and detect the condition in your middle-aged patients; and to treat the condition aggressively and effectively in all your patients with the new knowledge and medications we now have available.