{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:42:51Z","timestamp":1784698971887,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004383, 82004386"],"award-info":[{"award-number":["82004383, 82004386"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National key research and development program","doi-asserted-by":"publisher","award":["2021YFC1712804"],"award-info":[{"award-number":["2021YFC1712804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as<jats:italic>Reynoutria japonica Houtt.<\/jats:italic>,<jats:italic>Veratrum nigrum L.<\/jats:italic>, and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (&amp;lt;10, 10\u201325, 40\u201350, \u2265 60\u2009mg\/kg\/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats (<jats:italic>p<\/jats:italic>&amp;lt;\u20090.05). Resveratrol (&amp;lt;10\u2009mg\/kg\/day) significantly increased the BMD of the total body (MD\u2009=\u20090.01, 95% CI: 0.01 to 0.01,<jats:italic>p<\/jats:italic>&amp;lt;\u20090.001). In terms of improving the parameters related to micro-CT, resveratrol (40\u201350\u2009mg\/kg\/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing (<jats:italic>p<\/jats:italic>&amp;lt;\u20090.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin (<jats:italic>p<\/jats:italic>&amp;gt;\u20090.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats (<jats:italic>p<\/jats:italic>=\u20090.002) but did not improve the whole-body BMD of 3-month-old rats (<jats:italic>p<\/jats:italic>=\u20090.17).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2023.1234756","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T21:40:35Z","timestamp":1690494035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence"],"prefix":"10.3389","volume":"10","author":[{"given":"Jinlong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianke","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangxin","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.3928\/01477447-20220719-03","article-title":"Osteoporosis: an update on screening, diagnosis, evaluation, and treatment","volume":"46","author":"Sabri","year":"2023","journal-title":"Orthopedics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s40273-020-00965-9","article-title":"An updated systematic review of cost-effectiveness analyses of drugs for osteoporosis","volume":"39","author":"Li","year":"2020","journal-title":"PharmacoEconomics"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/s00198-022-06626-1","article-title":"A systematic review of cost-effectiveness analyses of sequential treatment for osteoporosis","volume":"34","author":"Yu","year":"2023","journal-title":"Osteoporos Int"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"9465","DOI":"10.3390\/ijms23169465","article-title":"Current status of the diagnosis and management of osteoporosis","volume":"23","author":"Aibar-Almaz\u00e1n","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ecl.2021.03.009","article-title":"Postmenopausal osteoporosis","volume":"50","author":"Arceo-Mendoza","year":"2021","journal-title":"Endocrinol Metab Clin N Am"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s13346-022-01222-6","article-title":"Bone regeneration in osteoporosis: opportunities and challenges","volume":"13","author":"Patel","year":"2023","journal-title":"Drug Deliv Transl Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e12956","DOI":"10.1111\/cpr.12956","article-title":"Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis","volume":"54","author":"Jiang","year":"2021","journal-title":"Cell Prolif"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1007\/s00198-022-06454-3","article-title":"Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis","volume":"33","author":"Xiao","year":"2022","journal-title":"Osteoporos Int"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The global prevalence of osteoporosis in the world: a comprehensive systematic review and meta-analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J Orthop Surg Res"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/14656566.2018.1428559","article-title":"New and developing pharmacotherapy for osteoporosis in men","volume":"19","author":"Gennari","year":"2018","journal-title":"Expert Opin Pharmacother"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1080\/14656566.2019.1594772","article-title":"Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss","volume":"20","author":"Fontalis","year":"2019","journal-title":"Expert Opin Pharmacother"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1080\/09553002.2020.1748911","article-title":"Amelioration of adjuvant-induced arthritis by exposure to low dose gamma radiation and resveratrol administration in rats","volume":"96","author":"El-Ghazaly","year":"2020","journal-title":"Int J Radiat Biol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"5166","DOI":"10.3390\/molecules25215166","article-title":"Recent advances in synthesis, bioactivity, and pharmacokinetics of pterostilbene, an important analog of resveratrol","volume":"25","author":"Liu","year":"2020","journal-title":"Molecules"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"117422","DOI":"10.1016\/j.lfs.2020.117422","article-title":"Resveratrol promotes osteogenesis via activating SIRT1\/FoxO1 pathway in osteoporosis mice","volume":"246","author":"Jiang","year":"2020","journal-title":"Life Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1006\/bbrc.1998.9870","article-title":"Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells","volume":"253","author":"Mizutani","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1002\/jbmr.4115","article-title":"Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized, placebo-controlled trial","volume":"35","author":"Wong","year":"2020","journal-title":"J Bone Miner Res"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41387-018-0059-4","article-title":"Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial","volume":"8","author":"Bo","year":"2018","journal-title":"Nutr Diabetes"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e1003583","DOI":"10.1371\/journal.pmed.1003583","article-title":"The prisma 2020 statement: an updated guideline for reporting systematic reviews","volume":"18","author":"Page","year":"2021","journal-title":"PLoS Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE's risk of bias tool for animal studies","volume":"14","author":"Hooijmans","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e0142021","DOI":"10.1371\/journal.pone.0142021","article-title":"Determinants of the efficacy of cardiac ischemic preconditioning: a systematic review and meta-analysis of animal studies","volume":"10","author":"Wever","year":"2015","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"108856","DOI":"10.1016\/j.abb.2021.108856","article-title":"Effect of resveratrol and mesenchymal stem cell monotherapy and combined treatment in management of osteoporosis in ovariectomized rats: role of SIRT1\/FOXO3a and Wnt\/\u03b2-catenin pathways","volume":"703","author":"Elseweidy","year":"2021","journal-title":"Arch Biochem Biophys"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1093\/abbs\/gmu103","article-title":"Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-\u03baB signaling pathway","volume":"46","author":"Feng","year":"2014","journal-title":"Acta Biochim Biophys Sin Shanghai"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3892\/ijmm.2017.3208","article-title":"Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity","volume":"41","author":"Feng","year":"2018","journal-title":"Int J Mol Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.3892\/mmr.2015.3581","article-title":"Resveratrol prevents osteoporosis in ovariectomized rats by regulating microRNA-338-3p","volume":"12","author":"Guo","year":"2015","journal-title":"Mol Med Rep"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1080\/08952841.2018.1522126","article-title":"Resveratrol restores the level of key inflammatory cytokines and RANKL\/OPG ratio in the femur of rat osteoporosis model","volume":"31","author":"Khera","year":"2019","journal-title":"J Women Aging"},{"key":"ref26","volume-title":"The research of resveratrol to prevent osteoporosis in ovariectomized rats by adjusting the activity of antioxidant enzymes","author":"Li","year":"2016"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"76","DOI":"10.59566\/IJBS.2005.1076","article-title":"Effects of resveratrol on bone mineral density in ovarectomized rats","volume":"1","author":"Lin","year":"2005","journal-title":"Int J Biomed Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1089\/jmf.2005.8.14","article-title":"Effects of trans-resveratrol from polygonum cuspidatum on bone loss using the ovariectomized rat model","volume":"8","author":"Liu","year":"2005","journal-title":"J Med Food"},{"key":"ref29","volume-title":"Effects of resveratrol on osteoprotegerin and osteoprotegerin ligand expression of femurs in ovariectomized rats","author":"Wang","year":"2006"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3969\/j.issn.1006-7108.2021.05.001","article-title":"Effect of resveratrol on the development of osteoporosis in ovariectomized rats","volume":"27","author":"You","year":"2021","journal-title":"Chin J Osteoporos"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3969\/j.issn.0529-1356.2012.05.018","article-title":"Protective effects and mechanisms of resveratrol on the rats suffering with osteoporosis","volume":"43","author":"Zhang","year":"2012","journal-title":"Acta Anat Sin"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1120272288","DOI":"10.1177\/2058738420941762","article-title":"Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4\/nuclear factor kappa B pathway by increasing miR-92b-3p expression","volume":"34","author":"Zhang","year":"2020","journal-title":"Int J Immunopathol Pharmacol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.3969\/j.issn.1671-4695.2022.18.002","article-title":"Effects of estradiol combined with resveratrol on bone mineral density and biomechanics in ovariectomized osteoporosis rats","volume":"21","author":"Zhang","year":"2022","journal-title":"J Clin Exp Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1017\/S0007114513003115","article-title":"Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus","volume":"111","author":"Zhao","year":"2014","journal-title":"Br J Nutr"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"86","DOI":"10.7619\/jcmp.202019025","article-title":"Role of resveratrol in promoting cell proliferation of rats with ovariectomized osteoporosis","volume":"24","author":"Zhou","year":"2020","journal-title":"J Clin Med Pract"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/nyas.12145","article-title":"Osteogenic effects of resveratrolin vitro: potential for the prevention and treatment of osteoporosis","volume":"1290","author":"Mobasheri","year":"2013","journal-title":"Ann N Y Acad Sci"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"11492","DOI":"10.1074\/jbc.M110.198713","article-title":"Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-\u03baB ligand (RANKL) activation of NF-\u03baB signaling and inhibit osteoclastogenesis in bone-derived cells","volume":"286","author":"Shakibaei","year":"2011","journal-title":"J Biol Chem"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"16876","DOI":"10.1073\/pnas.0604234103","article-title":"Depression induces bone loss through stimulation of the sympathetic nervous system","volume":"103","author":"Yirmiya","year":"2006","journal-title":"PNAS"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.2106\/JBJS.20.00989","article-title":"Oxidative stress and osteoporosis","volume":"103","author":"Kimball","year":"2021","journal-title":"J Bone Joint Surg"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3390\/antiox12040915","article-title":"Oxidative-stress-related genes in osteoporosis: a systematic review","volume":"12","author":"Le\u00f3n-Reyes","year":"2023","journal-title":"Antioxidants (Basel)"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1234756\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T05:35:15Z","timestamp":1729834515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2023.1234756\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":40,"alternative-id":["10.3389\/fnut.2023.1234756"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2023.1234756","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"article-number":"1234756"}}