
Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. The present study explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well‐documented, randomized, placebo‐controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3‐year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01–1.62; p = 0.039). The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates.
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