Data Sheet 1_Preclinical effects of naringin on bone outcomes in animal models of osteoporosis: a systematic review and meta-analysis.docx

Certainty of evidence was assessed using an adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for preclinical animal studies.</p>Results<p>Naringin was associated with higher bone mineral density (BMD; (SMD = 2.30, 95% CI 1.88–2.72), bone volume fraction (BV/TV; SMD = 3.36, 95% CI 2.17-4.55), trabecular thickness (Tb.Th; SMD = 2.35, 95% CI 1.49-3.21), trabecular number (Tb.N; SMD = 3.30, 95% CI 1.98-4.61), and lower trabecular separation (Tb.Sp; SMD = -2.92, 95% CI -4.01 to -1.83).

Favourable pooled effects were also observed for several bone turnover markers. Prediction intervals excluded the null for BMD and C-terminal telopeptide of type I collagen (CTX-1) but crossed the null for most other outcomes. Sensitivity analyses generally preserved the direction of the pooled effects, although potential small-study effects were detected for several structural outcomes.

Dose-response associations varied across analytical specifications and did not establish a stable optimal dose. Certainty of evidence was low for CTX-1 and very low for all other outcomes.</p>Conclusion<p>Naringin showed a broad favourable preclinical signal for improving bone density, trabecular microarchitecture, and selected bone turnover markers in animal models of osteoporosis. The evidence was comparatively more robust for BMD and CTX-1, whereas heterogeneity, methodological limitations, and low certainty of evidence reduced confidence in the magnitude and reproducibility of effects across experimental settings.

These findings support further investigation of naringin as a potential skeletal protective agent, with well-designed preclinical studies needed to clarify reproducibility, dose‐response relationships, and translational relevance.</p>Systematic Review Registration<p>identifier CRD420261419299.</p>