Effects of exercise on bone health parameters in ovariectomized rats: A systematic review and meta-analysis

Background: Osteoporosis is a major health concern in postmenopausal women, characterized by reduced bone mineral density (BMD) and deteriorated bone microarchitecture due to estrogen deficiency. While pharmacological therapies are widely used, exercise represents a promising non-pharmacological approach to enhancing bone health. Purpose: This systematic review and meta-analysis evaluated the effects of exercise interventions on BMD and bone-related biomarkers in ovariectomized (OVX) rats as a model of postmenopausal osteoporosis. Methods: A comprehensive search was conducted across Scopus, PubMed, and ScienceDirect databases for studies investigating exercise interventions in OVX rats. Random-effects meta-analyses were performed using Review Manager 5.4 to pool mean differences in BMD and bone-related biomarkers. Subgroup analyses were conducted according to skeletal site and exercise modality. Risk of bias was evaluated using the SYRCLE tool. Results: Twenty-nine studies were included, involving treadmill running (55%), swimming (14%), resistance training (7%), jumping exercises (17%), and downhill running (7%). Across 14 studies, OVX rats demonstrated significant reductions in BMD at the vertebrae, femur, and tibia (MD: 0.03 g cm-2, P < 0.0001). Exercise partially reversed these deficits, yielding small but significant BMD at skeletal sites (MD: -0.01 g cm-2, P < 0.0001). Moderate-intensity treadmill and jumping/plyometric exercise showed significant effects on BMD. Exercise decreases bone resorption biomarkers (TRACP/TRACP5b/TRAP, CTX-1/β-CTX/NTX) and balances bone formation biomarkers (OCN, ALP, P1NP), while regulating PPARγ, Wnt/β-catenin, sirtuins, RANKL, and oxidative stress. Conclusion: Exercise interventions significantly mitigate OVX-induced bone loss, improve BMD, and positively influence biomarkers of bone remodeling, supporting its role as a potential non-pharmacological strategy for managing postmenopausal osteoporosis.