Resistance Exercise at Different Periods Before and After Ovariectomy Attenuates Bone Loss in Ovariectomized Mice.

Abstract

Postmenopausal osteoporosis is a prevalent metabolic bone disease characterized by reduced bone density, decreased bone strength, and increased fracture risk. While resistance exercise has been shown to attenuate osteoporosis, the optimal timing for exercise intervention remains unclear. This study aimed to investigate whether the timing of resistance exercise-initiated before, after, or throughout the period of estrogen deficiency-differentially affects bone health in ovariectomized mice, and to provide a theoretical basis for postmenopausal osteoporosis prevention and treatment with exercise. Five-week-old female C57BL/6 mice were assigned to one of five groups: sham operation group (SHAM), ovariectomized sedentary group (OVX), pre-OVX +exercise group (Pre-OVX+E), OVX +exercise group (OVX+E), and post-OVX + exercise group (Post-OVX+E). Mice performed a ladder-climbing resistance exercise protocol at the designated time points. Bone microstructure was assessed by Micro-CT, bone biomechanical properties by three-point bending test, osteogenic and osteoclast-related factors by RT-qPCR, western blot assays and Enzyme-linked immunosorbent assay (ELISA) analysis, and potential regulatory molecular mechanisms through RNA-Seq analysis. All three exercise groups could enhance the bone biomechanical properties and improve the bone microstructure of ovariectomized mice. The Post-OVX+E group performed better than the other exercise groups on microstructure in both cortical bone and cancellous bone. The Post-OVX+E group and the OVX+E group showed better effects on the expression of osteogenic and osteoclast-related factors. RNA-Seq analysis revealed that the ECM-receptor interaction pathway represented the common signaling pathway shared among groups. Resistance exercise at different periods before and after ovariectomy can attenuate bone loss in ovariectomized mice, with exercise after ovariectomy demonstrating superior protective benefits on bone. The mechanism underlying these beneficial effects may involve the ECM-receptor interaction pathway.