Association Between Bone Mineral Density and the Use of Nonsteroidal Anti-Inflammatory Drugs and Aspirin: Impact of Cyclooxygenase Selectivity

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Abstract
BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the Health ABC cohort (n = 2853). Significantly higher BMD was found in users of relative COX‐2 selective NSAIDs with aspirin (COX‐2/ASA) compared with nonusers. This suggests a role for COX‐2/ASA in osteoporosis. Introduction: The purpose of this study was to determine the relationship of nonsteroidal anti‐inflammatory drug (NSAID) use, by cyclo‐oxygenase selectivity (COX), and aspirin use on bone mineral density (BMD) in participants from the Health, Aging, and Body Composition (Health ABC) population‐based cohort. It is known that NSAIDs inhibit the COX enzyme and decrease production of prostaglandins, which are involved in regulation of bone turnover. COX has two isoforms, COX‐1 and COX‐2. Production of prostaglandins associated with bone loss is primarily mediated through the COX‐2 pathway. In addition, aspirin may have effects on bone independent of the prostaglandin pathway. Materials and Methods: NSAID (by COX selectivity) and aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men; 43.1% black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the purposes of this analysis, relative COX‐1 selective NSAIDs were defined as having a ratio of COX‐1 IC50 to COX‐2 IC50 of >1 in whole blood, and relative COX‐2 selective NSAIDs were defined as having a ratio of COX‐1 IC50 to COX‐2 IC50 of <1 in whole blood. Analysis of covariance was used to compare BMD across each NSAID use and aspirin use category adjusting for age, race, gender, weight, height, study site, calcium and vitamin D supplementation, Womac score, history of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking status. Results: After adjustment for possible confounders, current use of relative COX‐2 selective NSAIDs with aspirin was associated with higher BMD at the whole body (4.2%, 1.2–7.3 CI) and total hip (4.6%, 0.5–8.8 CI) by DXA and at both trabecular (34.1%, 15.4–52.7 CI) and cortical spine (12.8%, 2.3–23.3 CI) by quantitative computed tomography. Conclusions: Our data suggest that the combination of relative COX‐2 selective NSAIDs and aspirin is associated with higher BMD at multiple skeletal sites in men and women.