NSAID use may reduce effectiveness of osteoporosis therapies


Data from a cohort of 5000 patients indicates that NSAID use may negatively affect clodronate therapy in older women.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of osteoporotic fracture risk and limit the effectiveness of osteoporitic therapies, according to research results published in the Journal of Bone and Mineral Research.1

A posthoc analysis of data from a single-center, randomized trial assessing use of the bisphosphonate, clodronate, in older women, results of the study suggest use of nonsteroidal anti-inflammatory drugs (NSAIDs) blunted the majority of the observed benefit of clodronate on reducing the risk of fracture in these patients.

“We need to exercise some caution in extrapolating these data to more widely used bisphosphonates in osteoporosis, but given that concomitant usage of NSAIDs and bisphosphonates is relatively common, this could have major clinical consequences and result in a failure to reduce fracture risk as much as we had hoped,” said senior author Eugene McCloskey, MD, of Northern General Hospital, in the UK, in a statement.2

Contemporary data have drawn conflicting confusion over the effects of NSAIDs on risk of fracture. With previous research providing evidence of both a beneficial and detrimental effect, McCloskey and a team of fellow investigators sought to assess how use of concomitant NSAID might influence the efficacy of clodronate in a cohort of elderly, community-dwelling women.

The pilot study used as the basis for the analysis was a single-center, prospective, randomized, placebo-controlled study of clodronate 800 mg in community-dwelling women age at 75 years of age or greater aimed at assessing the efficacy of the intervention to reduce risk of fracture. At the conclusion of the 3-year trial, treatment with clodronate was associated with a 23% reduction in osteoporotic fracture risk.

Overall, the study provided investigators with data related to 5212 women for inclusion in their analyses, including 10082 who reported use of NSAIDs at baseline. Compared to their counterparts without NSAID use, those who reported use of NSAIDS were significantly younger (79 vs 80 years, P=.004), heavier (mean 66.7 vs 64.7 kg; P <.001), and had with higher femoral neck bone mineral density (FN-BMD, 0.66 vs. 0.64 g/cm2; P <.001).

In adjusted models, NSAID use was associated with a significant increase in osteoporotic fracture risk during the 3-year study period (HR, 1.27; [95% CI, 1.01-1.62]; P=.039) among the overall study population, but this increase in risk was not statistically significant among those randomized to placebo therapy (HR, 1.11 [95% CI, 0.81-1.51]). When assessing impact of NSAID use among those using clodronate, the apparent benefit of clodronate was not observed among those using NSAIDs (HR, 0.95 [955 CI, 0.65-1.41]; P=.081). Compared to those randomized to clodronate with no NSAID use, who still experienced a significant reduction in risk of osteoporotic fracture (HR, 0.71 [95% CI, 0.58-0.89]; P=.002).

In analyses assessing change in hip BMD at 3 years vs baseline, results indicated BMD loss during clodronate therapy was greater among women receiving NSAIDs (total hip: 2.75% vs. 1.27%, P=.078; femoral neck: 3.06% vs 1.12%, P=.028) and investigators pointed out this effect was not significantly different from that observed among women receiving placebo therapy.

“Although we found little evidence for NSAID use as a risk factor for incident osteoporotic fractures among elderly community-dwelling women, the observation that NSAID use significantly reduced the ability of clodronate to prevent bone loss and fractures is unique and of high clinical importance. The marked reduction in efficacy does not appear to be mediated by imbalances in baseline characteristics or lower compliance,” investigators wrote.

This article originally appeared on Endocrinology Network.


  1. Zheng Z, Johansson H, Harvey NC, et al. Potential adverse effect of nonsteroidal anti-inflamamtory drugs (NSAIDs) on bisphosphonate efficacy: An exploratory post hoc analysis from a randomized controlled trial of clodronate. J Bone Miner Res. Published online April 20, 2022. doi:10.1002/jbmr.4548
  2. Do pain relievers impede bone drug's efficacy? News release. Wiley. April 20, 2022. Accessed May 2, 2022. https://www.eurekalert.org/news-releases/949990
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