Osteo Drug Safe, Effective Over Long Haul

Study finds Fosamax works for 10 years and beyond

WEDNESDAY, March 16, 2004 (HealthDayNews) -- One of the longest controlled trials ever performed on the subject has found the osteoporosis drug alendronate worked well for a decade with no untoward side effects.

Once the drug was stopped, the benefits started dissipating, but only gradually.

"This is encouraging about the ability to use this on a long-term basis and that there didn't seem to be any harm to continue," says Dr. Henry G. Bone, lead author of the study appearing in the March 18 issue of the New England Journal of Medicine. "It also suggests that if somebody had to interrupt therapy, this isn't a crisis. The effect dissipates very slowly. It makes it no longer a supposition. We have some data."

"It will give people confidence that alendronate is a drug you can use and expect good results for up to 10 years, and that is three years more than the previous data had shown," adds Dr. Stephen Honig, director of the Osteoporosis Center at the Hospital for Joint Diseases in New York City. "That's important because it allays some of the fears that people had about alendronate perhaps producing brittleness of bone."

Because osteoporosis is a chronic condition that requires long-term treatment, it is helpful to have long-term data, Bone explains.

According to an accompanying perspective article, osteoporosis is fast becoming an epidemic with the aging of the world's population and the Westernization of much of the globe. A 50-year-old woman in the United States now has a 40 percent lifetime risk of suffering an osteoporotic fracture.

Osteoporosis is essentially the result of an imbalance in the pace of bone breakdown and bone replacement.

"Bone is constantly being remodeled where you're constantly replacing your bones, little pockets at a time," says Bone, who is director of the Michigan Bone and Mineral Clinic and head of endocrinology at St. John Hospital and Medical Center, both in Detroit. "There's supposed to be a balance between the amount that's removed and the amount replaced. If you get an imbalance over time, you have osteoporosis. You're removing more than you put back."

Alendronate, sold by Merck & Co. Inc. under the brand name Fosamax, works by preventing bone resorption, which is essentially when bone is being removed without being replaced.

"We are slowing down the breaking-down process from too much to the normal premenopausal rate," Bone says. "That lets formation catch up with resorption and helps stabilize the bone."

The current study, which was supported by Merck Research Laboratories, was extended so as to get results on 10 years of use in addition to five years of follow-up after discontinuation of the drug. The current article reports results on 247 women who participated in all phases of the study, from the beginning. Early phases of the trial also reported increases in bone density and decreases in the risk of fracture.

Women who were treated with 10 milligrams of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lower spine, 10.3 percent in the trochanter (the protrusion on the upper thigh), 5.4 percent at the neck of the hip, and 6.7 percent for the total hip measurement. Women who took 5 milligrams daily had smaller gains.

Women who stopped taking the drug experienced a gradual loss of effect as measured by bone density.

"In the course of doing this, some of the drug gets buried in the bone and doesn't get dug up again until that particular place is remodeled, which is years later," Bone says. "It's not surprising that if you stop taking the drug and there's still some of it, so to speak, buried in the bone, gradually some of that will be reabsorbed and released, and there will be some effect, but less than if you continue to take the drug. We saw the measurements of bone remodeling activity increased after the drug was stopped, but not back up to the starting point. There was a residual benefit."

"This gives us 10-year safety data and 10-year efficacy data and [a] little bit of information about what happens when someone stops it, and all of that is new," says Dr. Paula Rackoff, assistant chief of rheumatology and director of the Osteoporosis Center at Beth Israel Medical Center in New York City.

While the study was a long-term one, it perhaps gives better guidance on how to treat women who are 65 or older than women who are in their early 50s with borderline indications of osteoporosis and no evident fracture risk. "If someone's 52, you will have to treat her for 25 years, so 10 years is a good start," Honig says.

More information

For more on osteoporosis medications, visit the National Osteoporosis Foundation. Meanwhile, the National Institutes of Health has a primer on the disease.

SOURCES: Henry G. Bone, M.D., director, Michigan Bone and Mineral Clinic, and head, endocrinology division, St. John Hospital and Medical Center, Detroit; Stephen Honig, M.D., director, Osteoporosis Center, Hospital for Joint Diseases, New York City; Paula Rackoff, M.D., assistant chief, rheumatology, and director, Osteoporosis Center, Beth Israel Medical Center, New York City; March 18, 2004, New England Journal of Medicine
Consumer News