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Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs ( NSAIDs ) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
Author(s) -
Zheng Zhangan,
Johansson Helena,
Harvey Nicholas C.,
Lorentzon Mattias,
Vandenput Liesbeth,
Liu Enwu,
Kanis John A.,
McCloskey Eugene V.
Publication year - 2022
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4548
Subject(s) - medicine , post hoc analysis , placebo , hazard ratio , bisphosphonate , randomized controlled trial , confidence interval , lower risk , adverse effect , osteoporosis , relative risk , bone mineral , femoral neck , alternative medicine , pathology
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. We 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%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN‐BMD, 0.66 versus 0.64 g/cm 2 , p < 0.001). 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). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81–1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65–1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58–0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip −2.75% versus −1.27%, p = 0.078; femoral neck −3.06% versus −1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. 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. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).