Effects of kaempferol on bone loss in animal models of osteoporosis: a systematic review and meta-analysis

Purpose: Osteoporosis remains a major global health challenge, necessitating the search for safe and effective therapeutic leads. Kaempferol, a natural flavonoid, has shown potential in bone health management. This systematic review and meta-analysis aimed to quantitatively evaluate the preclinical efficacy of kaempferol in mitigating bone loss in animal models of osteoporosis. Methods: Following PRISMA guidelines and PROSPERO registration (CRD420251273304), a comprehensive search was conducted across eight electronic databases up to January 2026. Twelve randomized controlled trials investigating kaempferol monotherapy in osteoporotic animal models (primarily OVX rats) were included. Methodological quality was assessed using SYRCLE's risk of bias tool, and meta-analysis was performed using Stata 18.0. Results: Kaempferol significantly increased femoral bone mineral density (BMD) (SMD = 2.86; 95% CI: 1.96-3.79; p < 0.001). It also significantly improved microarchitectural parameters (BV/TV, Tb.N, Tb.Th) and biomechanical properties (elastic modulus). Mechanistically, kaempferol elevated bone formation markers (P1NP), suppressed bone resorption markers (TRACP, CTX), and modulated the RANKL/OPG signaling axis. Subgroup analyses confirmed consistent osteoprotective effects across various dosages and intervention durations. Conclusion: Preclinical evidence robustly demonstrates that kaempferol effectively preserves bone mass and microarchitectural integrity while enhancing mechanical strength. These findings establish kaempferol as a promising natural bioactive candidate for osteoporosis management and provide a rigorous evidence-based foundation for its clinical translation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251273304.