". . .Among those whose femoral neck T scores were more than −2.0, more fractures occurred in the treatment group (n = 22, 3.3%) than in the placebo group. . . ."
-- JAMA (1998)
We'll see -- but I suspect Dr. Thomas A. Musliner's notes and files, related to this article he co-authored -- are at the heart of the current Graves Fosamax® ONJ Bellwether dispute. Note that -- as early as 1998, this JAMA published study concluded (among other matters) that:
. . . .Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. . . .
The effect of treatment on the risk of clinical fractures depended on initial femoral neck BMD [bone mineral density] (P = .01 for the interaction) (Table 3 and Figure 4). Alendronate significantly reduced the risk of clinical fractures by 36% (RH, 0.64; 95% CI, 0.50-0.82; placebo-treatment difference, 6.5%; NNT, 15) in women whose initial femoral neck T score was −2.5 or less. However, 4 years of alendronate did not significantly affect risk of clinical fracture in those with higher BMD. We observed a 22% lower risk of clinical fracture in those whose T scores were more than 2.0 SDs below the normal mean (RH, 0.78; 95% CI, 0.65-0.94; placebo-treatment difference, 3.3%; NNT, 30) (Figure 4). Alendronate did not decrease the risk of fracture among subjects whose initial T scores were greater than −2.5 (RH, 1.08; 95% CI, 0.87-1.35). . . .
In post hoc analyses, alendronate reduced the risk of hip fractures by 56% among women with a femoral neck T score of −2.5 or less: 18 (2.2%) in the placebo group vs 8 (1.0%) in the alendronate group (RH, 0.44; 95% CI, 0.18-0.97; placebo-treatment difference, 1.2%; NNT, 81). There was no reduction in risk among those whose femoral neck T scores were more than −2.5: 6 (0.4%) in the placebo group vs 11 (0.8%) in the alendronate group (RH, 1.84; 95% CI, 0.70-5.36).
The effect of alendronate on the risk of wrist fractures also varied by baseline femoral neck BMD. There was no significant reduction among women with a T score of −2.5 or less: 38 (4.7%) in the placebo and 34 (4.2%) in the alendronate group (RH, 0.88; 95% CI, 0.55-1.40). Similarly, we observed no reduction in risk among women with T scores of −2.0 to −2.5: 20 (2.8%) in the placebo group vs 27 (3.7%) in the alendronate group (RH, 1.33; 95% CI, 0.75-2.4). Among those whose femoral neck T scores were more than −2.0, more fractures occurred in the treatment group (n = 22, 3.3%) than in the placebo group (n = 12, 1.7%; RH, 1.9; 95% CI, 1.0-4.0; placebo-treatment difference, 1.6%).
Stratification of the results by BMD of the total hip, spine, or other sites indicated that alendronate consistently decreased the risk of nonspine fractures among women with BMD T scores of −2.5 or less but not among women with BMD T scores of more than −2.0. The apparent threshold for a significant effect of treatment on risk of clinical fractures varied by BMD measurement site from a T score of −2.5 or less at the femoral neck and spine to less than −2.0 at the total hip. . . .
In women with low BMDbut without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD. . . .
Note here that (as a Merck employee!) Dr. Musliner would have -- as of 1998 -- signed on to the idea that there is no reduction in fracture risk, for women who do not have full-on osteoporosis -- i.e., women with "osteopenia". If the fracture risk reduction benefit doesn't exist in women with osteopenia -- and that fact was known to a Merck employed medical expert by 1998 -- this could be a game changer.
It is, I recall, undisputed that Mrs. Graves -- when first put on Fosamax -- had only osteopenia. I think this is the sort of evidence the plaintiffs are driving toward. We'll know by January 3, 2011:
Stay tuned.
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