Protective effects and mechanisms of puerarin in ovariectomized animal models of osteoporosis: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Osteoporosis is a prevalent systemic metabolic disease, and osteoporotic fractures severely compromise patients' health and quality of life. Postmenopausal osteoporosis is a major form of primary osteoporosis in women and is primarily attributable to estrogen deficiency. Ovariectomized animal models are widely used to reproduce estrogen deficiency-induced bone loss and microarchitectural deterioration. Puerarin, a natural isoflavone extracted from the traditional Chinese herb Pueraria lobata (kudzu), exhibits antioxidant, anti-inflammatory, and bone-metabolism-modulating pharmacological properties. Although some studies have conducted meta-analyses of puerarin in rat models of osteoporosis, there is a lack of analysis on bone microarchitecture and mechanism-related indicators. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effects of puerarin in female ovariectomized animal models of osteoporosis and to synthesize the potential mechanisms underlying its bone-protective effects. METHODS: Seven databases (PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP) were systematically searched. The methodological quality of included studies was assessed using the SYRCLE risk-of-bias tool. Statistical analyses were performed with STATA 14.0. Primary outcomes included bone mineral density (BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), bone volume fraction (BV/TV), and connectivity density (Conn.D). Secondary outcomes encompassed bone metabolism markers, inflammatory cytokines, and oxidative stress indices. Sensitivity analyses and subgroup analyses were conducted to explore sources of heterogeneity. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: A total of 22 studies comprising 447 animals were included in this review, and all osteoporotic models were constructed via bilateral ovariectomy. Puerarin significantly improved BMD, Tb.N, Tb.Th, BV/TV, and Conn.D, and reduced Tb.Sp. For secondary outcomes, puerarin significantly decreased serum levels of bone turnover markers (BGP, PINP, CTX-I, TRACP-5b, and RANKL) and increased OPG levels. Additionally, puerarin significantly reduced pro-inflammatory cytokines (IL-6, TNF-α) and malondialdehyde (MDA), while elevating antioxidant enzyme activities (SOD, GSH-Px). CONCLUSION: Puerarin showed protective effects in female ovariectomized animal models of osteoporosis, potentially through suppression of bone resorption, normalization of high bone turnover, and anti-inflammatory and antioxidant actions. Because the evidence was heterogeneous and limited to ovariectomy models, further rigorous preclinical studies are required before clinical translation. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251236043.