Strategies for Osteoporosis Management in a Primary Care Setting
- Pharmacologic Therapies for Prevention and Treatment
- Fall Prevention
- Estrogen Replacement and Selective Receptor Modulators
Pharmacologic Therapies for Prevention and Treatment
Primary health care should routinely address bone health. Young adults should be encouraged to achieve normal peak bone mass through:
- adequate dietary calcium (1000 mg daily)
- weight-bearing exercise
- maintenance of normal body weight and reproductive function
- hormone replacement (often in the form of estrogen containing oral contraceptives) in young women who experience prolonged amenorrhea
For newly menopausal women, estrogen replacement is the standard of practice to prevent bone loss. There is evidence to suggest that initiating estrogen therapy in older women may be of benefit to bone mass, although the maximum benefits are achieved through early menopausal hormone replacement and maintenance of estrogen replete state long-term. For example, The Study of Osteoporotic Fractures provided epidemiological data that bone loss continues in older women and that estrogen may decrease this loss.(ref 20) The average rate of bone loss from the total hip in this study was sufficient to increase the risk of hip fracture by 21% per 5 years in women aged 80 years or older. However, compared with nonusers, current estrogen users had a 33% lower age-adjusted mean rate of loss at the total hip. There are no completed long-term clinical trials of estrogen in older women; however the Womens Health Initiative is an ongoing study to determine the risk-benefit ratio of estrogen use in older postmenopausal women.
Testosterone replacement for hypogonadal men preserves bone mass. Testosterone replacement for age-related declines in testosterone levels in healthy older men is currently being studied to determine the risk/benefit profile. Studies are underway to determine if there is a role for bisphosphonate therapy in prevention of bone loss due to hypogonadal state from the anti-hormonal therapies for the treatment of prostate cancer.
Osteoporosis Management(ref 4, 19) is evolving. There is consensus that calcium and vitamin D intake is needed to increase bone mass. There are three FDA approved, non-sex steroid treatments for for postmenopausal osteoporosis; alendronate, risedronate and etidronate. Likely, other oral bisphosphonates will receive FDA approval. Data were recently published that support the combination of estrogen and bisphosphonate as additive to increase bone mass.(ref 27) Calcitonin and sodium monofluorophasophate plus calcium have also been shown to reduce vertebral fractures. The table below lists the dosing and side effects of these nonhormonal treatment options.
Calcium Intake |
1500 mg daily (through diet and supplements) |
Vitamin D |
800 units daily is needed to increase bone mass |
Alendronate* |
Dosage: 10 mg daily to treat osteoporsis and 5 mg daily to prevent bone loss in women who are unable to take estrogen replacement. There are data to show that alternative alendronate dosing of 35 mg twice weekly, or 70 mg once weekly results in similar increases in bone density at one year to daily alendronate therapy, but with less gastrointestinal adverse reactions.(ref 21) (:also see EULAR meeting highlights) |
Risedronate |
Dosage: The recommended regimen is 5 mg orally daily for the treatment and prevention of postmenopausal osteoporosis"glucocorticoid-induced osteoporosis. |
Etidronate (FDA approved for treatment in Pagets Disease) |
Efficacy: Ealier studies showed efficacy in preventing vertebral fractures with cycled etidronate; however later data suggested that long-term etidronate may lead to impairment in new bone formation. |
Calcitonin |
Dosage:200 units, or one metered puff daily alternating nostrils |
Sodium Monofluorophosphate Plus calcium |
Dosage: Not available for patient use except under research protocols. Efficacy:: Although shown to reduce vertebral fractures, the effects on bone mineral density of the total hip were not significant.(ref 23) |
*Recent data support the use of alendronate 10 mg daily in the treatment of steroid-induced osteoporosis in both women and men.(ref 25) The dose of 5 mg daily has been shown to prevent accelerated bone loss in newly postmenopausal women, and may be useful for women who are unable to take estrogen due to history of estrogen-sensitive cancers or clotting disorders.(ref 26)
In addition to oral therapy, bisphosphonate treatment is also possible via intravenous infusion. Although not FDA approved for treatment of osteoporosis, pamidronate 30 or 60 mg infused intravenously over 2 hours every three months for two years has been shown to increase bone mineral density of the spine and hip by roughly 11% and 5.5% respectively.(ref 28) Ibandronate has been given by intravenous push rather than lengthy infusion, but is not yet available in the U.S. for clinical use.(ref 29)
Weight-bearing exercise has been shown to increase bone mass, strengthen muscle, and reduce the risk of falls. There is a role for exercise prescriptions in osteoporosis management. The National Osteoporosis Foundation offers an exercise program via video cassette that includes safe and effective exercises that can be performed in the home setting.
Is it reasonable to implement an osteoporosis treatment program in the setting of a recent fracture? Our experience to date is yes. At the Rehabilitation Center of the Johns Hopkins Geriatrics Center, the post-fracture admission orders include calcium and vitamin D supplementation. Bisphosphonate therapy in this setting has been difficult due to the high prevalence of gastroesophageal reflux and constipation. We currently defer bisphosponate or calcitonin therapy until the acute and subacute rehabilitation is complete, which is usually one to two months post-fracture.
Fall Prevention
For those at risk for falls, a fall prevention strategy is warranted to reduce the number of fall-related fractures. A multi-disciplinary approach includes both medical and physical assessments.(ref 30) Medications are reviewed to determine if any are impairing judgment, balance, or postural hemodynamic stability. Orthostatic and postprandial hypotension are considered. Vision and hearing assessment may target appropriate intervention. Gait assessment is performed during physical therapy evaluation. Training with assistive devices and the use of rubber soled shoes often improve fall risk. Physical therapy should include an exercise program for muscle strengthening and physical reconditioning. A home safety evaluation is used to identify dangers from throw rugs, inadequate lighting, and cluttered walkways, and to provide in-home safety equipment such as bathroom grab bars and raised toilet seats.
Estrogen Replacement and Selective Receptor Modulators
Patient compliance is limited by side effects of breast tenderness, weight gain, and vaginal bleeding associated with progestin co-therapy, as well as the increasing evidence that long-term estrogen use is associated with increased risk of breast cancer. However for the majority of women, the benefits of long-term estrogen outweigh the side effects and risks. All forms of estrogen replacement offer benefit if given in proper dose; patient preference, cost, and compliance are considered in the choice of therapy. For a woman who has undergone hysterectomy, estrogen therapy alone is needed. For a woman with an intact uterus, progestin cotherapy prevents endometrial hyperplasia. This can be achieved with daily progestin such as medroxyprogesterone acetate 2.5 mg daily, or 5 mg daily if vaginal bleeding occurs with the lower dose. Alternatively, progestin can be cycled either monthly or quarterly in doses of medroxyprogesterone acetate 5 to 10 mg daily for two weeks. Cycled progestin therapy results in scheduled vaginal bleeding that typically lasts for several days to one week. Over time, the amount of bleeding and the duration decrease, and many women can switch from cycled progestin to daily low dose in one to two years. Recent FDA approved forms of hormonal therapy include oral plant derived estrogens, oral natural progesterone, and a combination estradiol"progestin skin patch.
The largest impact on health from estrogen may relate to cardiovascular disease protection. The Heart and Estrogen"Progestin Replacement Study (HERS) recently published the results of randomized estrogen"progestin replacement for a mean of 4.1 years in 2763 women with established coronary disease.(ref 31) While there were no significant differences between the hormone and placebo groups in the primary outcomes of myocardial infarction and coronary heart disease death, there was a time trend that was significant, with more coronary heart events in the hormone group at year one, and fewer in years 4 and 5. The hormone group experienced 11% net lower LDL cholesterol and 10% higher HDL cholesterol than the placebo group. As a result of these data the research team has elected to continue collecting data on this cohort of women, expecting that the benefits of estrogen as secondary prevention of coronary heart disease requires long-term treatment. In addition to benefits to lipids and direct effects of estrogens on coronary artery atherosclerosis and vasodilatation, long-term estrogen use has been shown to prevent central obesity that may be associated with glucose intolerance.(ref 32)
A recent area of active research in the benefits of estrogen replacement is cognition, and prevention of dementia. In basic science studies, estrogens have been shown to promote neuronal survival and dendritic sprouting, increase acetylcholine activity, and prevent cerebral ischemia. Epidemiological data support a role for estrogen to improve cognition, prevent dementia,(ref 33) although studies on the efficacy of estrogen to treat dementia have contradictory results with the most recent placebo controlled study showing no significant treatment effect.(ref 34) It is possible that the role of estrogen in cognitive function is similar to that in bone metabolism, preventive effects rather than treatment once clinically significant disease is present.
Educating women that the risk of death from hip fracture is equal to the risk of death from breast cancer enhances compliance with long-term estrogen. Indeed, the risk of breast cancer is a large detriment to long-term compliance with estrogen use. A recent metaanalysis of studies involving over 54,000 women found that the risk for breast cancer increases by 2 extra cases by age 70 in 1000 women who have used hormone replacement for five or greater years.(ref 35) Cases of breast cancer per 1000 women for 10 and 15 years of estrogen exposure were 6 and 12, respectively. Thus, the epidemiological data suggest increased risk of breast cancer with five or greater years. For women with positive family history of breast cancer, the Iowa Women's Health Study did not find an increase in breast cancer with hormone replacement.(ref 36) However, it is difficult to persuade a woman with a family history of breast cancer to initiate estrogen. The Women's Health Initiative, a randomized trial of hormone replacement, is expected to provide data on the overall benefits such as primary prevention from coronary heart disease and risks of estrogen such as breast cancer in the Year 2007.
Selective estrogen receptor modulators such as raloxifene 60 mg daily offer choice to women who are unable to take estrogen. The effects of raloxifene on bone and lipids are comparable to estrogen replacement.(ref 37) There appear to be no growth promoting effects on breast or endometrium, thus reducing the risk profile of hormone replacement. The down side to raloxifene is that hot flushes are not improved over Placebo, and the risk of clotting is at least comparable to estrogen. Cost is also an issue, with estrogen/progestin therapy roughly $25 per month, whereas raloxifene is over $60. As there are no long-term data on the benefits and risks of these newer pharmacologic agents, it is reasonable to recommend more traditional estrogen and progestin treatments as initial hormone replacement, and limit selective estrogen receptor modulator therapy to those who do not tolerate estrogen therapy or who are unwilling to use estrogen due to increased risk of breast cancer. For example, many women who have first degree relatives with breast cancer will not consider estrogen, although there are no data to support increased risk of breast cancer due to estrogen beyond that of their family history.
A study of tamoxifen use in older nursing home residents found that 10 mg daily was associated with a lower rate of hip fracture than in women not receiving such therapy, but that a dose of 20 mg was similar to no therapy.(ref 38)