{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:09:07Z","timestamp":1789711747689,"version":"4.0.1"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["ZB2025002"],"award-info":[{"award-number":["ZB2025002"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Naringin, a flavanone glycoside derived from citrus plants and other botanical sources, has shown potential skeletal protective effects in preclinical studies. However, quantitative evidence regarding its effects across different osteoporosis models and skeletal outcomes remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic review and meta-analysis of controlled preclinical animal studies evaluating naringin in osteoporosis-related bone-loss models was conducted. Five databases were searched from January 2010 to May 2026. Standardised mean differences (SMDs) expressed as Hedges\u2019\n                      <jats:italic>g<\/jats:italic>\n                      , were pooled using random-effects models. Twenty-six reports representing 24 independent experimental cohorts were included. Certainty of evidence was assessed using an adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for preclinical animal studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Naringin was associated with higher bone mineral density (BMD; (SMD = 2.30, 95% CI 1.88\u20132.72), 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats: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\u2010response relationships, and translational relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>identifier CRD420261419299.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1945663","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:38:46Z","timestamp":1789709926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical effects of naringin on bone outcomes in animal models of osteoporosis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Chang","family":"Tan","sequence":"first","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Zhi","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3390\/jcm10010152","article-title":"Denosumab discontinuation and the rebound phenomenon: a narrative review","volume":"10","author":"Anastasilakis","year":"2021","journal-title":"J. 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