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-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/cm2, 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)

Does chronic low-dose aspirin use benefit bone health? A cross-sectional study on patients with type 2 diabetes mellitus

Abstract Introduction Numerous studies have reported the striking result that aspirin use is associated with higher bone mineral density (BMD), suggesting its potential as a population-wide osteoporosis prevention measure. Therefore, this study aimed to examine the impact of chronic low-dose aspirin use on bone remodeling biomarkers and BMD in an aging population. Materials and methods Between September and November of 2019, clinical data regarding the medication use, serum bone remodeling biomarkers, and BMD of 567 consecutively hospitalized patients, a minimum of 50 years old with type 2 diabetes mellitus (T2DM), were collected. The cross-sectional associations between chronic low-dose aspirin use and serum concentrations of bone remodeling biomarkers and BMD were estimated separately using linear regression. Potential confounding variables were controlled for, including age, sex, and comorbidities. Results Low-dose aspirin users had significantly lower serum bone alkaline phosphatase (BAP) concentrations than non-users (82.44 ± 28.03 U/L vs 90.71 ± 32.79 U/L, p = 0.025). On the other hand, low-dose aspirin users had insignificantly higher vertebral BMD (0.95 ± 0.19 vs 0.91 ± 0.21, p = 0.185), femoral neck BMD (0.80 ± 0.15 vs 0.78 ± 0.17, p = 0.309) and Ward’s triangle BMD (0.46 ± 0.14 vs 0.44 ± 0.13, p = 0.209), regardless of adjustment. Conclusions This cross-sectional study demonstrated that chronic use of low-dose aspirin was associated with significantly lower serum concentrations of BAP in hospitalized patients with T2DM. The mechanism causing the insignificantly higher BMD observed in chronic aspirin users in this study and the significant increments in BMD reported in previous studies requires further clarification in other clinical trials