The results of a decade-long drug trial, published Mar. 17 in the New England Journal of Medicine, indicate that women worried about brittle bones have an alternative to controversial hormone-replacement therapy for long-term protection against hip and leg fractures. In the longest clinical trial ever conducted for the prevention of this bone disease in post-menopausal women, Merck's (MRK) Fosamax was able to increase bone density for up to 10 years.
In fact, it even maintained some protective effects five years after women went off it. "I was very, very excited by this paper," says Dr. Harold Rosen, director of the Osteoporosis Prevention & Treatment Center at Beth Israel Deaconess Medical Center in Boston.
Osteoporosis is a chronic thinning of bones that causes them to become brittle and break. Some 44 million people in the U.S. have some form of the disease, about 80% of them women. As a result, a 50-year-old woman has a 40% lifetime risk of a hip or leg fracture, and one woman in three over 80 will suffer a hip fracture. Osteoporosis usually starts in women after menopause, when their bodies stop manufacturing the estrogen needed to maintain healthy bones.
"THERAPEUTIC OPTION." Estrogen-replacement therapy was long considered the gold standard for preventing bone loss in this group, but recent evidence has shown that the strategy carries an increased risk of breast cancer, heart disease, and stroke. "A number of women who have been taking estrogen for the prevention of osteoporosis will now be thinking about shortening their exposure," says Dr. Henry Bone, chief of endrocrinology at St. John Hospital & Medical Center in Detroit, and lead author of the Fosamax report. "This study shows that [Fosamax] is certainly one therapeutic option."
Fosamax was the first of a group of drugs called bisphosphonates approved for the prevention of osteoporosis in 1995. These drugs bind to bone crystals and inhibit the breakdown of bone.
The New England Journal report is based on a clinical trial started in 1991 that was initially meant to last only three years but was extended three times to provide long-term data on the treatment's usefulness. A total of 247 women went through the trial's full 10 years. Two groups received either 5 mg or 10 mg of the drug daily for the full 10 years, while a third group, which had received 20 mg for the first three years, was switched to 5 mg in years 3 through 5 and to a placebo for years 6 through 10.
HOW LONG IS SAFE? After 10 years, the women receiving 10 mg increased their bone mass density significantly: by 13.7% in the spine, by 10.3% in the hips, and by 5.4% in the legs. Smaller increases were recorded for the women receiving 5 mg daily. The placebo group experienced a small decrease at all sites five years after they went off the drug, but they were still better off than if they had not received any treatment. No meaningful side effects were found in those taking the drug, Bone says.
The study still hasn't settled just how long patients should take the drug, however. Beth Israel's Rosen says the trial does support the safety and efficacy of Fosamax treatment for 10 years. "On the other hand," he notes, "if you stop the drug after five years, the bone density is still pretty well maintained," indicating that it has long-term residual effects. "That means there's still a substantial worry about whether there might be some eventual downside if you keep taking this drug over a long term." By Catherine Arnst in New York