{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:57Z","timestamp":1786512477347,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To systematically evaluate the anti-osteoporotic efficacy of curcumin in preclinical models and utilize an exploratory small-sample machine learning (ML) framework to examine potential contributors to heterogeneity and generate preliminary dose\u2013duration hypotheses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Following PRISMA guidelines, we searched eight databases for controlled\n                      <jats:italic>in vivo<\/jats:italic>\n                      animal studies in validated osteoporosis models that compared curcumin monotherapy with saline or vehicle controls and reported extractable bone-related outcomes, including bone mineral density (BMD) and trabecular microarchitecture. Methodological quality was assessed using the SYRCLE tool. In addition to random-effects meta-analysis, an exploratory ML framework incorporating SHapley Additive exPlanations (SHAP) and Gaussian Process Regression (GPR) was employed to examine associations between nine study-level features and effect estimates and to explore potential non-linear dose\u2013response patterns after normalization to the Human Equivalent Dose (HED).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-three studies were included. Meta-analysis revealed that curcumin significantly elevated femoral BMD [standardized mean difference (SMD) = 2.73, P &amp;lt; 0.001], preserved trabecular microarchitecture, and enhanced biomechanical strength. Curcumin was also associated with changes in bone-remodeling and oxidative stress-related markers. Based on only 23 study-level observations, exploratory ML suggested that body weight had the largest model-dependent contribution (mean |SHAP| = 0.201). GPR modeling suggested a bell-shaped dose-response relationship, with the fitted response reaching a local maximum at an HED of approximately 32 mg\/(kg\u00b7d) and an intervention duration of 8\u201312 weeks. These model-derived findings should not be interpreted as validated optimal dose or duration estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Curcumin exerts potent, multi-target osteoprotective effects that are associated with improved bone remodeling and oxidative stress-related indices. The exploratory integration of ML with meta-analysis suggested that biological characteristics and dosage may contribute to variability in treatment effects. However, because the ML component was constrained by the limited number of study-level observations, these model-derived findings should be regarded as hypothesis-generating signals and should not be interpreted as independently validated predictors or clinical dosing recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420251269951.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1893878","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:40:08Z","timestamp":1786509608000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated meta-analysis and exploratory small-sample machine learning to evaluate curcumin against osteoporosis: a preclinical evidence-based study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuzhuo","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Nursing, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]},{"name":"The Clinical Medical College, Chengdu University of Chinese Traditional Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongru","family":"Wei","sequence":"additional","affiliation":[{"name":"Gongxian Traditional Chinese Medicine Hospital","place":["Yibin, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nursing, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]},{"name":"Department of Critical Care Medicine, Honghui Hospital, Xi\u2019an Jiaotong University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2021.05.016","article-title":"Update on osteoporosis screening and management","volume":"105","author":"Anam","year":"2021","journal-title":"Med Clinics North America"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115772","article-title":"Molecular and cellular mechanisms of osteoporosis","volume":"24","author":"Zhivodernikov","year":"2023","journal-title":"Int J Mol 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