UPDATED: 03.24.10 @ 8:40 pm EDT -- The New York Times is just out with a story on the below, and it's a good one. Do go read it, for more background.
Because the study was conducted, in part, by employees of Merck (and funded in part by it, as well), the maker of Fosamax® (and funded by other makers of these osteoporosis drugs), we should look very carefully at the power claimed, for the conclusions offered. However, I think the independent editor writing for the New England Journal of Medicine may safely be trusted when she intones, thus:
. . . .This new report has important strengths. The investigators evaluated studies that were randomized and placebo-controlled, involving 14,195 women and 55,000 person-years of observation. The degree of exposure to bisphosphonates is known, providing a denominator that was lacking in previous reports. The alendronate extension data that compared 5 years and 10 years of alendronate use provide some reassurance regarding reported associations between subtrochanteric or diaphyseal fracture and long-term bisphosphonate treatment.
However, several important limitations in the study by Black, et al., diminish our ability to draw definitive conclusions. In most cases, radiographs were not available to evaluate features of atypia. Only a minority of women received more than 3 to 4 years of bisphosphonate treatment, and some received a lower dose of alendronate (5 mg) than is commonly prescribed. Most important, as the authors acknowledge, because of the rarity of atypical femoral fractures, the study's statistical power was extremely low, which underscores the difficulty in detecting rare complications, even in very large clinical trials. The experience with bisphosphonates highlights the importance of postmarketing surveillance studies to detect the emergence of rare side effects of drugs that are widely used for very common chronic diseases. . . .
Although detailed recommendations are beyond the scope of this editorial, it is reasonable to consider drug holidays with careful observation for most patients with osteoporosis who are receiving long-term therapy, particularly those whose bone-turnover markers indicate substantially reduced levels. However, we must also balance evidence of persistent antifracture efficacy after discontinuation with data showing that the use of alendronate for 10 years, as compared with 5 years, was associated with significantly fewer new vertebral fractures and nonvertebral fractures in patients with a bone mineral density T score of –2.5 or below.
Because subtrochanteric fractures are so rare, many questions remain unanswered. Research is needed to address the true incidence of such fractures, the pathogenetic importance of bisphosphonate use and other risk factors, the detection of incipient fractures, and appropriate medical and surgical management. . . .
As ever, more to come -- the FDA is likewise undertaking a review, the results of which may be available by late June 2010.
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