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abstract & commentary
Synopsis: Alendronate reduces fracture risk comparably in women with osteoporosis manifested as a vertebral crush fracture, and in women with osteoporosis defined radiographically.
Source: Black DM, et al. J Clin Endocrinol Metab 2000;85:4118-4124.
The purpose of the present investigation was to compare the effect of alendronate treatment on fracture risk reduction in women with existing vertebral fracture with that in women without existing vertebral fracture but with a bone mineral density T score less than -2.5. A total of 6459 women were enrolled from 11 clinical centers in the United States. Of these, 3658 met criteria for osteoporosis, either on the basis of bone mineral density as assessed by dual energy x-ray absorptiometry (DEXA), or on the basis of having had a previous vertebral crush fracture. Women were randomly assigned to receive either placebo or alendronate and followed for three-four years. In the first year, women in the alendronate arm received 5 mg daily, and in later years 10 mg daily. The data were analyzed by a true intention-to-treat analysis. Regardless of the definition of osteoporosis (bone mineral density vs previous vertebral fracture), the risk reduction was comparable and impressive. The relative risk for vertebral fracture in the alendronate treated group was 0.52 (0.42-0.66) and for hip fracture 0.47 (0.26-0.79). Black and colleagues also determined how long it took for the risk reduction to manifest. The risk reduction was first significant for clinical vertebral fracture by month 12, and for hip fracture by month 18.
COMMENT by Sarah L. Berga, MD
The results of this study are not surprising, but they are reassuring. The study demonstrates that alendronate is as effective in preventing fracture in women with radiological evidence for osteoporosis as in women with clinical evidence. Furthermore, this is the first study to show that alendronate reduces hip fracture risk. Black et al also point out in the discussion that alendronate is likely to confer a "continuous gradient of benefit" in women with low bone mass. Thus, a woman does not have to have a bone mineral density T score less than -2.5 to benefit from alendronate use. Furthermore, given the relatively prompt risk reduction, the benefit is not thought to be strictly attributable to an increase in bone density. Slowing of the bone-remodeling rate may also play a critical role.
This study still begs to answer the issue of exactly who should be given alendronate and for how long. It is easier to decide who might benefit than it is to say for how long therapy should continue. There are no long-term (> 10 years) studies of alendronate or any other bisphosphonate. With regard to selecting those most likely to benefit, my approach is to recommend estrogen therapy as the first line of defense because of its multiple other benefits in addition to bone preservation. I reserve bisphosphonate use for women whose bone mineral density remains low despite adequate estrogen repletion, for those who meet criteria for osteoporosis (as defined clinically or radiologically) before initiating estrogen therapy (because the use of both agents gives additional benefit), or for those who cannot or will not take estrogen.