{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:43:03Z","timestamp":1793900583424,"version":"4.8.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoporosis is highly prevalent among postmenopausal women and is characterized by a progressive 1\u20132% annual decline in bone mineral density (BMD). This deterioration contributes to more than 8.9 million fractures globally each year. The condition arises from an imbalance between bone formation and resorption. Emerging evidence suggests that probiotics may positively modulate bone metabolism through gut microbiota regulation, yet high-quality clinical data directly linking probiotic use to bone turnover markers remains limited. This meta-analysis investigates the effects of probiotic supplementation on bone formation and resorption markers in osteoporotic individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta-analysis were conducted on 15 randomized controlled trials (RCTs) involving 1,432 participants. The studies assessed various probiotic strains, dosages, and intervention periods ranging from 8 weeks to 12 months. Pooled effect sizes were calculated for key bone formation markers\u2014procollagen type 1 N-terminal propeptide (P1NP) and osteocalcin\u2014and resorption markers, including C-terminal telopeptide of type I collagen (CTX-I), N-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b (TRAP-5b). Subgroup and dose\u2013response analyses were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Probiotic supplementation significantly improved bone metabolism. Bone formation markers showed notable increases, including a significant rise in P1NP (MD = +8.4 \u03bcg\/L; 95% CI: 3.1\u201313.7) and osteocalcin. Bone resorption markers, especially CTX-I, demonstrated significant reductions (SMD = \u22120.35; 95% CI: \u22120.52 to \u22120.18). Multi-strain probiotic formulations produced greater improvements in both bone formation and resorption compared with single-strain interventions. A clear dose\u2013response trend was observed, with higher probiotic doses correlating with stronger increases in P1NP. Subgroup analyses showed that postmenopausal women experienced more pronounced benefits than mixed-gender groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis. Multi-strain formulations and higher dosages yielded the greatest improvements, particularly among postmenopausal women. These findings support probiotics as a promising adjunctive strategy for improving bone health and potentially reducing fracture risk. However, longer-term trials and strain-specific mechanistic studies are needed to confirm clinical utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1738378","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:53:08Z","timestamp":1767768788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis"],"prefix":"10.3389","volume":"15","author":[{"given":"Yingjia","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jundao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hewei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.21608\/ejhm.2023.280204","article-title":"Levels of serum procollagen type-1 amino terminal propeptide and C-terminal cross-linked telopeptide of type-1 collagen in children","volume":"90","author":"Afify","year":"2023","journal-title":"Egyptian J. Hosp. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s12602-023-10185-0","article-title":"Understanding osteoporosis: Human bone density, genetic mechanisms, gut microbiota, and prospects","volume":"16","author":"Ahire","year":"2024","journal-title":"Probiotics Antimicrobial Proteins"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00284-023-03526-3","article-title":"Quality management of probiotics: ensuring safety and maximizing health benefits","volume":"81","author":"Ahire","year":"2024","journal-title":"Curr. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.3390\/biomedicines12051075","article-title":"Intersecting paths: unraveling the complex journey of cancer to bone metastasis","volume":"12","author":"Arakil","year":"2024","journal-title":"Biomedicines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1017\/S0007114523002362","article-title":"Effect of probiotics on postmenopausal bone health: a preclinical meta-analysis","volume":"131","author":"Bose","year":"2024","journal-title":"Br. J. Nutr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"743","DOI":"10.3390\/cells11040743","article-title":"Role of dietary supplements and probiotics in modulating microbiota and bone health: the gut-bone axis","volume":"11","author":"de Sire","year":"2022","journal-title":"Cells"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.3390\/biomedicines12081635","article-title":"Mechanistic insights and therapeutic strategies in osteoporosis: a comprehensive review","volume":"12","author":"Elahmer","year":"2024","journal-title":"Biomedicines"},{"key":"B8","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12891-025-08276-w","article-title":"Association between fibrinogen-to-albumin ratio and bone metabolism markers (\u03b2-CTX and P1NP) in Chinese individuals with osteoporotic fracture: a cross-sectional investigation","volume":"26","author":"Feng","year":"2025","journal-title":"BMC Musculoskeletal Disord."},{"key":"B9","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1007\/s11657-022-01061-5","article-title":"UK clinical guideline for the prevention and treatment of osteoporosis","volume":"17","author":"Gregson","year":"2022","journal-title":"Arch. osteoporosis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"101593","DOI":"10.1016\/j.bonr.2022.101593","article-title":"Circadian rhythm of markers of bone turnover in patients with chronic kidney disease","volume":"16","author":"Hansen","year":"2022","journal-title":"Bone Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"117487","DOI":"10.1016\/j.bone.2025.117487","article-title":"Reference values for cross-linked C-telopeptide of type 1 collagen and pro-collagen type 1 N-terminal propeptide in children and adolescents: Results from the Canadian Health Measures Survey","volume":"196","author":"Kim","year":"2025","journal-title":"Bone"},{"key":"B12","doi-asserted-by":"publisher","first-page":"816","DOI":"10.3390\/nu16060816","article-title":"Use of complementary and alternative medicine in patients with rare bone diseases and osteoporosis","volume":"16","author":"Kocijan","year":"2024","journal-title":"Nutrients"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2410478","DOI":"10.1080\/19490976.2024.2410478","article-title":"Microbiome\u2019s role in musculoskeletal health through the gut-bone axis insights","volume":"16","author":"Li","year":"2024","journal-title":"Gut Microbes"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1012087","article-title":"The effects and significance of gut microbiota and its metabolites on the regulation of osteoarthritis: Close coordination of gut-bone axis","volume":"9","author":"Liu","year":"2022","journal-title":"Front. Nutr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41413-023-00264-x","article-title":"Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis","volume":"11","author":"Lyu","year":"2023","journal-title":"Bone Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.3390\/antiox12020373","article-title":"Oxidative stress and natural antioxidants in osteoporosis: novel preventive and therapeutic approaches","volume":"12","author":"Marcucci","year":"2023","journal-title":"Antioxidants"},{"key":"B17","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1007\/s43393-023-00208-w","article-title":"Advances in probiotics research: mechanisms of action, health benefits, and limitations in applications","volume":"4","author":"Prajapati","year":"2024","journal-title":"Syst. Microbiol. Biomanufacturing"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.3390\/jcm11092382","article-title":"Secondary osteoporosis and metabolic bone diseases","volume":"11","author":"Sobh","year":"2022","journal-title":"J. Clin. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3390\/nu16030461","article-title":"Effects of multispecies probiotic supplementation on serum bone turnover markers in postmenopausal women with osteopenia: A randomized, double-blind, placebo-controlled trial","volume":"16","author":"Vanitchanont","year":"2024","journal-title":"Nutrients"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1487998","article-title":"Effects of probiotic supplementation on bone health in postmenopausal women: A systematic review and meta-analysis","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Endocrinol."},{"key":"B21","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 WHO diagnostic criteria: a systematic review and meta-analysis","volume":"33","author":"Xiao","year":"2022","journal-title":"Osteoporosis Int."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1617459","article-title":"The gut microbiota in osteoporosis: dual roles and therapeutic prospects","volume":"16","author":"Xie","year":"2025","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1738378\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:53:09Z","timestamp":1767768789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1738378\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":22,"alternative-id":["10.3389\/fcimb.2025.1738378"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1738378","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"article-number":"1738378"}}