Efficacy of Epimedii Folium and related preparations in experimental osteoporosis: a systematic review and meta-analysis

Abstract

Epimedii Folium and related extracts have shown osteogenic, antiresorptive, antioxidant, and anti-inflammatory activities in experimental studies. This systematic review and meta-analysis evaluated their efficacy in rodent models of osteoporosis. PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data were searched from their inception to 13 June 2026. Controlled in vivo studies using rat or mouse models of osteoporosis or experimentally induced bone loss were eligible. Random-effects models generated Hedges’ standardized mean differences (SMDs) with 95% confidence intervals (CIs). The risk of bias was assessed using the SYRCLE tool. The protocol was registered in PROSPERO (CRD420261428223). Sensitivity analyses examined heterogeneity, the influence of the Qi 2019 estimate, and the effects of multi-arm dependence, preparation type, disease model, duration, and dose. Certainty was appraised using an adaptation of GRADE for preclinical animal evidence. Twenty-nine independent rodent studies were included. Femoral BMD increased (20 comparisons from 9 studies; SMD = 1.66, 95% CI: 1.07–2.25; 95% prediction interval [PI]: −0.61 to 3.93; I 2 = 73.77%). Excluding Qi 2019 reduced the SMD to 1.44 (95% CI: 0.96–1.92), while a three-level study-cluster robust model yielded an SMD of 2.25 (95% CI: 0.40–4.10). The average effects favored several regional BMD, microarchitectural, and biomechanical outcomes, but the majority of PIs crossed the null. PINP was not significant. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) assessment found that the majority of judgments were unclear, with nine domain-level judgments rated as high risk; certainty was very low. Random-effects pooled estimates favored the examined oral Epimedii Folium-derived preparations for several regional BMD, trabecular microarchitecture, and ex vivo biomechanical outcomes in rodent models. However, wide prediction intervals, chemical and model heterogeneity, small study sizes, incomplete reporting, and correlated multi-arm comparisons limit confidence in the pooled effect magnitudes. Chemically standardized preparations and exposure-informed dosing are needed before clinical translation. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261428223 , identifier CRD420261428223.