NSAIDs reduce efficacy of clodronate in preventing bone loss, fractures
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In a cohort of women, NSAID use significantly decreased the efficacy of the bisphosphonate clodronate for preventing bone loss and fractures, according to findings from a post hoc analysis.
According to study background, NSAIDs have been shown to possess a weak but beneficial effect on bone health, including fracture risk.
“But many epidemiological studies are likely confounded,” Eugene V. McCloskey, MD, FRCPI, professor of adult bone disease in the department of oncology and metabolism at the University of Sheffield, United Kingdom, and colleagues wrote.
The researchers performed a post hoc analysis of a randomized, placebo-controlled study that showed treatment with clodronate decreased osteoporotic fracture risk by 23%; their aim was to examine the relationship between NSAID use and fracture risk.
The researchers used baseline concurrent medication prescriptions to identify patients who used oral NSAIDs and included only verified, incident fractures.
Overall, of the 5,212 women enrolled, 20.8% reported use of NSAIDs at baseline. Compared with nonusers, women who used NSAIDs were younger (mean age, 79 years vs. 80 years; P = .004) and heavier (mean, 66.7 vs. 64.7 kg; P < .001) and had a higher femoral neck bone mineral density (0.66 vs. 0.64 g/cm2; P < .001).
In adjusted model results, NSAID use elevated osteoporotic fracture risk during the 3-year study period (HR = 1.27; 95% CI, 1.01-1.62; P = .039), although the increased risk did not reach statistical significance in the placebo group (HR = 1.11; 95% CI, 0.81-1.52).
For women treated with clodronate, the bisphosphonate failed to reduce osteoporotic fracture risk in those who used NSAIDs (HR = 0.95; 95% CI, 0.65-1.41; P = .81), but did reduce the risk in those who did not receive NSAIDs (HR = 0.71; 95% CI, 0.58-0.89; P = .002).
Among women with hip BMD repeated at 3 years, BMD loss while on clodronate therapy was increased in those receiving NSAIDs compared with nonusers (eg, total hip –2.75% vs. –1.27%; P = .078; femoral neck, –3.06% vs. –1.12%; P = .028), with no significant difference observed for women who received placebo.
“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 researchers concluded. “The marked reduction in efficacy does not appear to be mediated by imbalances in baseline characteristics or lower compliance. Although possible mechanisms need further exploration, there is an urgent need to examine this interaction in studies of other bisphosphonates in osteoporosis and other bone diseases.”
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