Bavachin Mitigates Bone Loss via RANKL Inhibition and Runx2 Activation in a Rat Model of Post-menopausal Osteoporosis

Background: Globally, post-menopausal osteoporosis poses a major health challenge, primarily affecting elderly women because of its connection to lowered bone mineral density and increased susceptibility to fractures. This skeletal disorder not only compromises the quality of life but also contributes to a substantial socio-economic and healthcare burden. Objectives: We examined the efficacy of bavachin, a plant-derived flavonoid estrogen mimic, in mitigating osteoporosis in ovariectomized Wistar rats. Materials and Methods: Osteoporotic conditions were established through bilateral ovariectomy (OVX), followed by treatment with bavachin. An additional OVX group received alendronate, a standard anti-osteoporotic drug, to serve as a reference for comparative efficacy. Critical molecular markers reflecting bone metabolism, such as osteocalcin, C-terminal telopeptide of type I collagen, alkaline phosphatase, and acid phosphatase, were quantified. Bone microarchitecture was examined using micro-computed tomography, while biomechanical strength was evaluated through a three-point bending test. Serum calcium and phosphorus levels were measured to examine bavachin’s influence on mineral homeostasis. Oxidative stress and inflammatory responses were analyzed by determining antioxidant enzyme activity and pro-inflammatory cytokine concentrations. Furthermore, the expression of bone remodeling regulators, such as osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), osterix (Osx), and runt-related transcription factor 2 (Runx2), was examined in treated and untreated OVX rats. Results: Bavachin treatment attenuated oxidative stress and inflammation, while improving bone turnover markers and mechanical properties. A decrease in RANKL expression and an upregulation of OPG, Osx, and Runx2 suggest that bavachin effectively modulates bone remodeling pathways and inhibits osteoclast-mediated bone resorption. Conclusion: Our findings demonstrate that bavachin exhibits significant anti-osteoporotic activity and may serve as a promising and safer alternative to conventional osteoporosis therapies.