COX2-independent and COX2-dependent effects of naproxen on bone quality, osteocytes, and fatigue fracture healing in male and female mice.

ABSTRACT: Regular non-steroidal anti-inflammatory drug (NSAID) use increases stress fracture risk, but the mechanisms remain unclear. Here, we used Ptgs2-Y385F mice, which lack cyclooxygenase 2 (COX2) enzyme activity, to test the hypothesis that naproxen decreases strain adaptive bone remodeling in a COX2-dependent manner and decreases bone toughness and fracture resistance through COX2-independent effects. MicroCT and mechanical testing showed minimal baseline differences between Ptgs2-Y385F and wild-type (WT) mice. Following non-damaging forelimb compression, naproxen decreased load-induced bone formation in WT, but not Ptgs2-Y385F mice, consistent with a COX2-dependent effect. In contrast, naproxen reduced bone toughness and post-yield deformation across genotypes and doses, supporting a COX2-ind

SUBMITTER: Ciuciu A 

PROVIDER: S-EPMC12407679 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature