Gut–Bone Axis Mediates Exercise Modality‐Dependent Suppression of Inflammatory Osteoclastogenesis in Ovariectomy‐Induced Bone Loss

Exercise is crucial for postmenopausal osteoporosis (PMOP) management, yet the comparative efficacy of different exercise modalities and the underlying mechanisms remain unclear. This study investigated the differential effects of distance-matched high-intensity interval training (HIIT) and moderate-intensity continuous exercise (MICE) on ovariectomy (OVX)-induced osteoporosis (OP) in mice. After 12 weeks of training, micro-CT analysis revealed that MICE, but not HIIT, significantly attenuated OVX-induced bone loss and microstructural deterioration. Crucially, only MICE suppressed osteoclastogenesis and reduced proinflammatory factors (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) expression in the femur, serum, and colon. Mechanistically, MICE uniquely restored gut microbiota (GM) diversity, mitigated dysbiosis, and enhanced intestinal barrier integrity by upregulating the expression of tight junction proteins (TJPs; ZO-1, occludin, and claudin-1), thereby…