Preventing Bone Loss with Medications in Postmenopausal Women

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The summary below is from the full report titled "Alendronate and estrogen–progestin in the Long-Term Prevention of Bone Loss: Four-Year Results from the Early Postmenopausal Intervention Cohort Study. A Randomized, Controlled Trial." It is in the 12 December 1999 issue of Annals of Internal Medicine (volume 131, pages 935-942). The authors are P. Ravn, M. Bidstrup, R.D. Wasnich, J.W. Davis, M.R. McClung, A. Balske, C. Coupland, O. Sahota, A. Kaur, M. Daley, and G. Cizza, for the Early Postmenopausal Intervention Cohort Study Group.

What is the problem and what is known about it so far?

Bone loss (osteoporosis) is common among women after menopause and can lead to fractures. Alendronate is a medicine that slows further bone loss in women who already have osteoporosis. Less bone loss also occurs in women without osteoporosis who take alendronate daily for up to 3 years, but the effect of taking it for more than 3 years is not known. Taking estrogen and progesterone after menopause (hormone replacement) also prevents bone loss.

Why did the researchers do this particular study?

To find out 1) whether alendronate continues to prevent bone loss after 3 years of use in postmenopausal women without osteoporosis and 2) what happens to women's bones after they stop taking alendronate.

Who was studied?

The researchers studied 1609 healthy (non-osteoporotic) postmenopausal women 45 to 59 years old.

How was the study done?

The researchers assigned women randomly to get either alendronate, estrogen–progestin, or placebo (a pill containing no active ingredient). After 2 years, they then randomly assigned the women who had taken alendronate either to continue the same dose or to switch to placebo. They measured the density of all women's bones at the start of the study and yearly for the next 4 years.

What did the researchers find?

Women who took placebo for the entire 4 years lost the most bone, and women who took alendronate the entire time actually gained bone. Women who stopped alendronate after 2 years began to lose bone but still were better off than those who took placebo the whole time. Bone density increased in women on hormone replacement at least as much as in those on alendronate. Side effects were the same with alendronate and placebo. As expected, side effects such as vaginal bleeding and breast tenderness occurred in women who took hormone replacement.

What were the limitations of the study?

Women on alendronate or placebo did not know which treatment they were taking, but those on hormone replacement did. This may have contributed to the side effects experienced by women taking hormones, since people who know they are on a medicine watch more closely for side effects. The study therefore had limited ability to compare the side effects of hormone replacement and alendronate. The study could not determine which treatment was most effective in preventing fractures because fractures occur so seldom in non-osteoporotic, younger, healthy postmenopausal women. A much larger study sample would be required to demonstrate a potential protective effect against fractures.

What are the implications of the study?

Alendronate continues to prevent bone loss in women without osteoporosis who take it continuously for 4 years; hormone replacement is at least equally effective. If women stop alendronate after 2 years, they begin again to lose bone but are still better off than if they had never taken the drug. Alendronate is an option for preventing osteoporosis in women who cannot or choose not to take hormone replacement.