In the September 2000 issue of your journal, a study by Tonino et al.(1) described the skeletal effects of 7 yr of treatment with alendronate. The study concluded that 7 yr of continuous treatment resulted in better skeletal effects than shorter therapy. I am concerned about the vertebral fracture rates that were presented in this paper. These fractures were confirmed by radiographs, but routine radiographs to check for vertebral fractures were not done. During the last 2 yr 3.3%/yr of women taking alendronate (10 mg/day) had a clinical vertebral fracture. This is higher than reported during the first 3 yr of this study, when the rate of morphometric vertebral fractures (defined by measurements from radiographs) was 2.1%/yr in the placebo group and 1.1%/yr in the alendronate groups (2). Direct statistical comparisons can't be made because there was no control group at yr 6 and 7.The method of ascertaining fractures was different in the two papers. Other studies suggest that clinical vertebral represent only about a third of total vertebral fractures. For example, in the Fracture Intervention Trial (FIT), among women with a baseline vertebral fracture, the rate of new clinical vertebral fractures was 1.7%/yr in women taking placebo and 0.8%/yr in women taking alendronate. The rate of morphometric fractures was 5%/yr in the placebo group and 2.7%/yr in the alendronate group (3). In the other arm of the FIT study, where women did not have a fracture at baseline, the morphometric vertebral fracture rate was 0.9%/yr in the placebo group and 0.5%/yr in the alendronate group. The clinical vertebral fracture rate was only 0.2%/yr in placebo group and 0.1%/yr in the alendronate group (4).In the women taking long-term alendronate, the rate of vertebral fractures was at least three times higher during yr 6 and 7 than during yr 1-3, despite the fact that the bone density of the spine was increasing. The rates were also higher than predicted from the data in the FIT study. The discrepancy cannot be explained by selection of more severe cases for the long-term study, because the baseline characteristics were similar. It also cannot be explained by aging of the population, because the FIT participants were older.There is no doubt that alendronate increases bone strength and decreases fracture rate during the first 4 yr of use, but after that the profound suppression of the bone formation rate may begin to have a negative effect. I hope these findings will lead to further studies of the long-term effect of alendronate on bone strength.
References1. Tonino RP, Meunier PJ, Emkey R, et al. 2000 Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. J Clin Endocrinol Metab. 85:3109 -3115. 2. Liberman UA, Weiss SR, Broll J, et al. 1995 Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med. 333:1437-1443. 3. Black DM, Cummings SR, Karpf DB, et al. 1996 Randomised trial of effect of alendronate on risk of fracture in women with ex...
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