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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

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‐documen...

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Autores principales: Zheng, Zhangan, Johansson, Helena, Harvey, Nicholas C., Lorentzon, Mattias, Vandenput, Liesbeth, Liu, Enwu, Kanis, John A., McCloskey, Eugene V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487988/
https://www.ncbi.nlm.nih.gov/pubmed/35441396
http://dx.doi.org/10.1002/jbmr.4548
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author Zheng, Zhangan
Johansson, Helena
Harvey, Nicholas C.
Lorentzon, Mattias
Vandenput, Liesbeth
Liu, Enwu
Kanis, John A.
McCloskey, Eugene V.
author_facet Zheng, Zhangan
Johansson, Helena
Harvey, Nicholas C.
Lorentzon, Mattias
Vandenput, Liesbeth
Liu, Enwu
Kanis, John A.
McCloskey, Eugene V.
author_sort Zheng, Zhangan
collection PubMed
description 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).
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spelling pubmed-94879882022-09-30 Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate Zheng, Zhangan Johansson, Helena Harvey, Nicholas C. Lorentzon, Mattias Vandenput, Liesbeth Liu, Enwu Kanis, John A. McCloskey, Eugene V. J Bone Miner Res Original Articles 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). John Wiley & Sons, Inc. 2022-04-20 2022-06 /pmc/articles/PMC9487988/ /pubmed/35441396 http://dx.doi.org/10.1002/jbmr.4548 Text en © 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). https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zheng, Zhangan
Johansson, Helena
Harvey, Nicholas C.
Lorentzon, Mattias
Vandenput, Liesbeth
Liu, Enwu
Kanis, John A.
McCloskey, Eugene V.
Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title_full Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title_fullStr Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title_full_unstemmed Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title_short Potential Adverse Effect of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
title_sort potential adverse effect of nonsteroidal anti‐inflammatory drugs (nsaids) on bisphosphonate efficacy: an exploratory post hoc analysis from a randomized controlled trial of clodronate
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487988/
https://www.ncbi.nlm.nih.gov/pubmed/35441396
http://dx.doi.org/10.1002/jbmr.4548
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