When, How, and Which One? Navigating the Maze of Osteoporosis Drugs
by Kristen Suthers, Ph.D
Osteoporosis ('porous bone') is a disease that causes bones to become fragile and increases their risk of breaking. It is a real condition with serious effects on women's health and quality of life; at the same time, it's a condition that has become over-advertised and over-treated. What is osteoporosis? When should it be treated and which treatment is best? In recent years, the number of drugs available to address osteoporosis has grown exponentially, creating a dilemma for many women about the appropriate use of these medications. Specifically, women want to know when it is appropriate to take a drug for osteoporosis, and which treatments are safest and most effective.
While all women begin to lose bone mass at the onset of menopause, all women don't develop osteoporosis. A woman is diagnosed with osteoporosis if her bone mineral density score is more than 2.5 standard deviations below the average for young adult, Caucasian women. Bone density is measured either by X-ray equipment called a DEXA machine or by an ultrasound machine. The U.S. Preventive Services Task Force recommends that women over 65 be screened for osteoporosis; for women under 65, the decision to test depends on her risk for osteoporosis, her health, and her family history. It is important to know that the American College of Sports Medicine has stated that it is unclear whether these criteria are appropriate for women of color. Until standardized criteria for osteoporosis are available for non-Caucasian populations, health care practitioners will likely continue to rely on the current diagnostic criteria.
Osteopenia identifies women with low bone mineral density who may be at-risk for osteoporosis; osteopenia is diagnosed when a woman's bone mineral density score is 1.0-2.5 standard deviations below the average. Although all women with osteoporosis once had osteopenia, not all women with osteopenia will develop osteoporosis. For this reason, and because it is unclear how much drugs benefit women at this stage, the World Health Organization recommends treating osteopenia only when other risk factors for fractures are apparent.
The Food and Drug Administration (FDA) has approved estrogen and progestin treatment only to prevent, not to treat, osteoporosis. Both estrogen alone and combinations of estrogen and progestin reduce the risk of osteoporosis and bone fracture in women. As yet, no evidence indicates that doses lower than 0.625 mg are effective in preventing fractures. Taking these hormones, however, increase a woman's risk of breast cancer, heart attack, stroke, and pulmonary embolism. Therefore, estrogen and progestin should be the last choice for osteoporosis prevention and should be used only when other types of prevention are contraindicated. Further, there is insufficient scientific evidence to support using other types of non-traditional estrogens (i.e., 17Beta-estradiol and 'bioidentical hormones') to prevent or treat osteoporosis.
Two other classes of medications have been approved only to treat women who already have osteoporosis: teriparatide and calcitonin. Teriparatide is a derivative of human parathyroid hormone (PTH), the primary regulator of calcium and phosphate metabolism in bones; 20 mg are injected daily to stimulate new bone formation and prevent vertebral and non-vertebral fractures in women with osteoporosis. Teriparatide (brand name: Forteo) is generally used only for women with severe osteoporosis, since side effects can include nausea, leg cramps, and dangerously high levels of calcium.
Calcitonin (not to be confused with calcium supplements) is a hormone that participates in calcium and phosphorus metabolism. While calcitonin prevents spinal fractures, it has not been shown to prevent hip, wrist, or other non-vertebral fractures. The hormone has been approved to treat women with osteoporosis, but the poor quality of the study evaluating calcitonin has made doctors reluctant to recommend it, and a review article in The New England Journal of Medicine stated that the use of calcitonin is generally not recommended. Women who do decide to take calcitonin must watch their intake of foods containing high calcium levels (e.g., milk, cheese), as excessive calcium in a woman's body may be dangerous. Calcitonin (brand names: Fortical or Miacalcin) can be administered as a nasal spray or as a skin injection; side effects may include nasal congestion and nausea.
Bisphosphonates are non-hormonal drugs that reduce the risk of fracture without the problems associated with hormone therapy. The drugs include Alendronate (brand name: Fosamax), Risendronate (brand name: Actonel), and Ibandronate (brand name: Boniva). Bisphosphonates have been approved by the FDA to prevent bone loss and fractures in the entire skeleton. Side effects vary by type of bisphosphonate, but generally can include damage to the esophagus (esophagitis) and muscle pain. The initial 150 mg dose may also cause a one-time response of muscle pain, joint aches, and low-grade fever.
While bisphosphonates seem to have fewer risks than hormones, they have not been around very long and clinical trials have not explored the effects on women of taking bisphosphenates for more than 10 years. A woman who starts taking bisphosphonates at menopause is likely to have to continue on the drugs for several decades to benefit, since the risk of debilitating fractures becomes most significant after age 70. The effects of bisphosphonates in pre-menopausal women have also not yet been extensively studied. Long-term bisphosphonate use may also begin to suppress, rather than stimulate, new bone formation, which can lead to brittle bones. A woman who decides to take bisphosphenates should carefully weigh the risks and benefits in consultation with her health care provider.
The use of most bisphosphonates requires a woman to take a pill every day and then sit upright for 30-60 minutes to prevent esophageal damage. Since its approval, Boniva has been heavily marketed because it can be taken once a month, a great advantage over daily pills. Women need to understand, however, that Boniva is only approved to prevent vertebral fractures; not other types of breaks such as hip or wrist fractures. In January, 2006, the FDA approved intravenous Boniva, which would be administered by a health care provider every three months. Despite Bonivaï¿½s advantages, it has been available to the general population for a short time, which means there is only limited information on its effectiveness in preventing bone loss and fractures in the general public.
Selective Estrogen Receptor Modulators
Sometimes referred to as "designer estrogens", the FDA has approved Selective Estrogen Receptor Modulators (SERM) for the treatment and prevention of osteoporosis. SERMS have different effects on estrogen receptors in different parts of the body, producing estrogenic effects in some sites, and acting like anti-estrogens in others. Raloxifene (brand name: Evista) seems to prevent osteoporosis without increasing the risk of cancers associated with other hormone treatments. But, raloxifene carries risks not found in non-hormonal drugs, including increased risk of blood clots, hot flashes, nausea, and leg cramps.
Large-scale, randomized, placebo-controlled trials over several years have indicated that raloxifene can prevent vertebral, but not non-vertebral fractures in post-menopausal women with osteoporosis. This is useful, as women who have multiple spinal fractures experience severe and debilitating pain, and difficulty with their daily activities. But the drug has not been shown to prevent non-vertebral fractures (such as hip or wrist fractures), and its efficacy has not been demonstrated in women without osteoporosis. It should be noted that raloxifene studies have not reported outcomes by race or ethnicity, since the studies lacked enough women of color to draw conclusive distinctions. Therefore, it is difficult to know how effective raloxifene is in preventing osteoporosis for women of color. While osteoporosis is more common among Caucasian and Asian women, the NWHN believes that these questions are important to all women regardless of ethnicity, and that any women's health study should include women of color.
In 2005, raloxifene's manufacturer, Eli Lilly, plead guilty to violating the Food, Drug, & Cosmetic Act and paid $36 million in fines for illegally promoting the drug to prevent and treat breast cancer and cardiovascular disease. The FDA has not approved raloxifene for these indications. This violation calls Eli Lilly's integrity into question. A woman who decides to take a drug to prevent vertebral fractures should try bisphosphonates first; she should only consider raloxifene if she has osteoporosis and cannot tolerate bisphosphonates. There's no reason to try raloxifene first, because no other benefit has been definitively shown.
The Bottom Line
There are clear indications that the pharmaceutical industry is looking to expand its market for osteoporosis drugs; the latest efforts are targeting "non-traditional" populations for osteopenia and osteoporosis screening, such as younger women and men. The NWHN believes many women under age 65 without critical risk factors are being inappropriately screened for osteopenia and osteoporosis; screening at this early age has not been shown to help prevent serious fractures unless there are significant risk factors present. We encourage women under age 65 to avoid bone density screening unless they are at an increased risk for osteoporosis based on multiple risk factors.
RISK FACTORS: (Source: National Institutes of Health Osteoporosis and Related Bone Diseases Resource Center).
Risk factors you cannot change:
- Gender. Your chances of developing osteoporosis are greater if you are a woman. Women have less bone tissue and lose bone faster than men because of the changes that happen with menopause.
- Age. The older you are, the greater your risk of osteoporosis. Your bones become thinner and weaker as you age.
- Body size. Small, thin-boned women are at greater risk.
- Ethnicity. Caucasian and Asian women are at highest risk. African American and Hispanic women have a lower but significant risk.
Family history. Fracture risk may be due, in part, to heredity. People whose parents have a history of fractures also seem to have reduced bone mass and may be at risk for fractures.
Risk factors you can change:
- Sex hormones. Abnormal absence of menstrual periods (amenorrhea), low estrogen level (menopause), and low testosterone level in men can bring on osteoporosis.
- Anorexia nervosa. This eating disorder increases your risk for osteoporosis.
- Calcium and vitamin D intake. A lifetime diet low in calcium and vitamin D makes you more prone to bone loss.
- Medication use. Long-term use of glucocorticoids and some anticonvulsants can lead to loss of bone density and fractures.
- Lifestyle. An inactive lifestyle or extended bed rest tends to weaken bones.
- Cigarette smoking. Cigarettes are bad for bones as well as the heart and lungs.
Alcohol intake. Excessive consumption increases the risk of bone loss and fractures.
There are a few other factors women need to consider when deciding whether to take osteoporosis drugs. The sequence of medications is important: some drugs cannot precede or follow others. In addition, the duration of treatment is critical in determining the effectiveness of prevention and treatment of osteoporosis: when a woman stops taking the drug, the preventive effects are lost. A woman shouldn't hesitate to ask her health care practitioner about the safety and efficacy of any osteoporosis medication, and inquire whether non-drug alternatives might be just as effective for her, based on her personal history and current health status. For more information go to the National Institutes of Health Osteoporosis and Related Bone Diseases Resource Center's website: http://www.osteo.org.
Kristen Suthers is a former NWHN Aging and Menopause Program Specialist