Epigenetic and hormonal effects of supervised combined aerobic and weight-bearing on bone health in postmenopausal women

BACKGROUND: Exercise training is increasingly recognized as a complementary therapy to support skeletal health in postmenopausal women. However, its epigenetic influence on circulating bone-related microRNAs and its hormonal impact on bone turnover remain insufficiently characterized. This study examined whether a 12-week supervised exercise program could modulate bone-related miRNAs, regulate key endocrine markers of bone remodeling, and enhance functional capacity. METHODS: Eighty-six participants aged 55-65 years without osteoporosis were assigned to either an exercise or control group. The intervention involved supervised sessions three times weekly for 12 weeks. Circulating levels of bone-related microRNAs (miR-21, miR-29b, miR-133a, miR-148a), biochemical markers of bone metabolism (osteocalcin, CTX, P1NP, bone-specific ALP), and functional performance (6-min walk and 30-s chair-stand tests) were assessed. RESULTS: The exercise group demonstrated pronounced epigenetic changes, with substantial upregulation of miR-21 and miR-29b (p < 0.001) and a modest increase in miR-133a (p = 0.02), while miR-148a remained unchanged. Hormonal markers indicated a shift toward bone anabolism, including higher osteocalcin (+29.4%), increased P1NP (+14.8%), and reduced CTX (-12.0%) (all p < 0.01), whereas bone-specific ALP showed no significant change. Functional performance improved significantly (+32.07 m in 6MWT; +27.8% in chair-stand). ANCOVA confirmed significant group differences for all outcomes except miR-148a and bone-specific ALP. No meaningful changes were observed in controls. CONCLUSIONS: Supervised combined aerobic and weight-bearing exercise produced coordinated epigenetic and endocrine adaptations that favor bone formation and improve physical function. These findings support its role as an effective complementary, non-pharmacological strategy to mitigate skeletal decline in postmenopausal women.