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a special report on the prevention and treatment of osteoporosis and a look at what's in store for the future
From screening to counseling, pharmacists can play a major role in the prevention and treatment of this disease
Remember all the times your mother told you to drink your milk? Hopefully, you were paying attention because a common misconception about osteoporosis is that it is always the result of bone loss, which occurs normally as we age; however, an individual who does not reach optimal (i.e., peak) bone mass during childhood and adolescence may develop osteoporosis without the occurrence of accelerated bone loss.
It is, therefore, important to first recognize osteoporosis as being largely preventable. Pharmacists can play a significant role in providing the necessary education to their patients about both the prevention and treatment of osteoporosis. Identifying patients who are at risk, providing bone mineral density (BMD) screening, educating patients receiving drug therapy on appropriate use and the consequences of noncompliance are all crucial steps pharmacists should take to increase the awareness of a disease that affects 10 million Americans.
The National Osteoporosis Foundation (NOF) estimates an additional 18 million Americans have low bone mass, placing them at high risk of developing osteoporosis. The disease causes more than 1.5 million fractures annually and costs this country nearly $14 billion each year.
Bone fractures and the complications that follow are serious consequences of osteoporosis. Mortality and morbidity following hip fractures are significant. One of every five persons who have a hip fracture will not survive a year.
Beverly Schaefer, R.Ph., owner of Katterman's Sand Point Pharmacy in Seattle lures her patients into her pharmacy for BMD testing with the line "How strong are your bones?" Since low BMD and existing fractures are the two greatest risk factors for additional fractures, it would only make sense for patients at risk to have a BMD screening (see box below).
Bone density data are most often reported as T-scores, which represent the number of standard deviations (SDs) from the normal young adult mean bone density values. The World Health Organization has defined osteoporosis as being present when the T-score is at least 2.5 SDs below the mean.
The results obtained by Schaefer are discussed with the patient and faxed to his or her physician. "The most important role for the pharmacist is patient education and referral," she noted. Her practice receives many referrals from outside her community and she sees it as a "golden opportunity for a pharmacist to have a one-on-one interaction with a patient."
"Up until five or six years ago, we were all taught that once patients had osteoporosis, it was too late to intervene, declared Michael McClung, M.D., FACE, director of the Oregon Osteoporosis Center. The results of all the clinical studies since 1994 make it very clear that even patients with severe osteoporosis receive a substantial benefit from being treated with any one of the several new treatments available, he explained.
The best candidates for therapy are high-risk patients. The patients at highest risk are postmenopausal women with osteoporosis defined by a T-score of 2.5 or lower and the presence of one or more fractures.
While osteoporosis is often thought of as a woman's disease, men also experience an age-related decline in BMD beginning in mid-life. Men and perimenopausal women with osteoporosis are more likely to have secondary causes for the bone loss than do postmenopausal women. The most common secondary causes for men are hypogonadism, use of glucocorticoids, and alcoholism. For women, the most common secondary causes include hypoestrogenemia, use of glucocorticoids, excess thyroid hormone, and anticonvulsant therapy.
McClung did suggest that lifestyle improvements, such as exercise, better diets, and calcium supplements, should increase BMD and/or slow the loss of BMD, leading to a reduction in fractures.
According to NOF, many adults consume only half the recommended daily intake of 1,000 to 1,200 mg of calcium. Pharmacists can play a vital role in counseling patients not only on the importance of calcium supplementation but also on prescription medications, which have been shown to interfere with calcium absorption. These medications include diuretics, corticosteroids, anticonvulsants, immunosuppressive medications, and nonsteroidal anti-inflammatory drugs. Other calcium stealers include sodium, smoking, alcohol, and excessive consumption of caffeine and soda.
Hormone replacement therapy (HRT) has shown significant efficacy in studies with BMD as the primary outcome. However, there is a scarcity of trials with fractures as the end point. McClung noted that many of the estrogen replacement therapies have lost their indication for treatment but remain an established approach for osteoporosis prevention.
Two bisphosphonates are currently available, alendronate (Fosamax, Merck) and risedronate (Actonel, Aventis). Both have been shown to increase BMD at the spine and hip in a dose-dependent manner, reduce the risk of vertebral fractures by 30% to 50%, and cut the risk of subsequent nonvertebral fractures in women with osteoporosis and adults with glucocorticoid-induced osteoporosis. In the new guidelines from the American College of Rheumatology, bisphosphonates are recommended as first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis.
Selective estrogen receptor modulators (SERMs), such as raloxifene (Evista, Lilly), have been shown to reduce the risks of vertebral fracture by 36%. The American Medical Association guidelines on managing osteoporosis state that bisphosphonates, and especially raloxifene, may be preferable in women who are at high risk for breast cancer, while estrogen and raloxifene are "attractive options" for those at risk for heart disease. However, it's important to note that the American Heart Association recently withdrew its recommendation that patients take estrogen for cardioprotection alone.
Calcitonin (Miacalcin, Novartis) is approved for the treatment of postmenopausal osteoporosis only and has had positive effects on BMD at the lumbar spine. According to McClung, calcitonin is used only when none of the other therapies can be tolerated because the other medications have been documented to reduce fractures more significantly.
Pharmaceutical manufacturers are working on new ways to treat and prevent osteoporosis. Therapies under investigation include new SERMs, new bisphosphonates, low-dose HRTs, a once-weekly formulation of risedronate, growth hormone, and vitamin D metabolites. But by far the most exciting development for the management of osteoporosis is Lilly's investigational bone formation drug Forteo (teriparatide injection, rDNA origin), which is a recombinant human parathyroid hormone (1-34).
All of the current medicines approved for osteoporosis are classified as antiresorptive drugs because they slow bone resorption or breakdown, the first step in the bone-remodeling process. While they are useful in reducing fracture risk, half of the patients who would have fractures still have them, declared McClung. "Forteo is the first bone-building drug that appears to actually cause repair in the architectural deterioration that has occurred with bone loss," he continued.
A better understanding of the process by which bone formation occurs has led to this new class of drugs that provide a burst of parathyroid hormone. Teriparatide works primarily to stimulate new bone formation by increasing the number and/or activity of bone-forming cells called osteoblasts. Key findings from a phase III clinical trial demonstrated that teriparatide significantly lowered fracture risk and significantly increased BMD compared with placebo in postmenopausal women with osteoporosis during an average of 18 months of treatment.
"The importance of the findings is particularly great for those women with osteoporosis who have already suffered an osteoporotic-related fracture. Those women are at an especially high risk of further osteoporotic fractures, and with each successive fracture, their risk of another fracture rises exponentially," noted Hunter Heath, M.D., U.S. medical director of endocrinology at Eli Lilly.
A Food & Drug Administration advisory committee has recommended approval of teriparatide for the treatment of osteoporosis in postmenopausal women. Lilly, in collaboration with Emisphere Technologies, has begun preclinical testing of an oral formulation of parathyroid hormone.
NOF, encouraged by the evidence of fracture reduction seen with teriparatide, noted that therapy appears to be effective when given for one to two years, although it may be necessary to follow up with an antiresorptive drug to maintain the benefits.
NOF also has several brochures available through its Web site at www.nof.org. These brochures can be useful to pharmacists to supplement oral counseling. They should also be made available to appropriate patients as they are discharged from the hospital following fracture-related injuries.
All women over 65 years of age
Postmenopausal women younger than age 65 with one or more risk factors (not including postmenopausal)
Those on long-term glucocorticoid therapy or other drugs associated with bone loss
Those receiving treatment of osteoporosis to establish skeletal stability and monitor treatment response
Those with a personal history of fracture
Those with a family history of osteoporosis (with a first-degree relative)
Source: National Osteoporosis Foundation, American Association of Clinical Endocrinologists
Tammy Chernin. BONING UP ON OSTEOPOROSIS. Drug Topics 2001;18:24.