{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:00:15Z","timestamp":1793073615221,"version":"4.5.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Daily supplementation with the probiotic\n Limosilactobacillus reuteri<\/jats:italic>\n ATCC PTA 6475 (\n L reuteri<\/jats:italic>\n ) vs placebo has previously been demonstrated to reduce bone loss in an estrogen deficiency mice model and older women, although the magnitude of the effect was small. We hypothesized that long-term treatment with\n L reuteri<\/jats:italic>\n could result in clinically relevant skeletal benefits in postmenopausal osteoporosis.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate whether daily supplementation with\n L reuteri<\/jats:italic>\n vs placebo could reduce early postmenopausal bone loss and whether the effects remained or increased over time during 2 years of treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n A double-blind, randomized, placebo-controlled clinical trial was conducted between December 4, 2019, and October 6, 2022, at a single center in Gothenburg, southwestern Sweden. Participants were recruited by online advertisements, and letters were sent to 10\u202f062 women aged 50 to 60 years. Responding women (n\u2009=\u2009752) underwent telephone screening, resulting in 292 women being invited to a screening visit. Of those who were screened, 239 women met all inclusion criteria and had no exclusion criteria.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n \n Capsules with\n L reuteri<\/jats:italic>\n in 2 doses, 5\u2009\u00d7\u200910\n 8<\/jats:sup>\n (low dose) or 5\u2009\u00d7\u200910\n 9<\/jats:sup>\n (high dose) colony-forming units, taken twice daily or placebo were administered. All capsules also included cholecalciferol, 200 IU.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the relative change in tibia total volumetric bone mineral density (vBMD) over 2 years. Secondary outcomes included relative change in areal BMD of the lumbar spine and total hip, bone turnover markers C-terminal telopeptide cross-links of collagen type I and type I procollagen intact N-terminal propeptide, as well as tibia trabecular bone volume fraction and cortical vBMD. Both intention-to-treat and per-protocol analyses were conducted.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 239 postmenopausal women (median age, 55 [IQR, 53-56] years) were included. Tibia vBMD (primary outcome), hip and spine vBMD, and tibia cortical area and BMD decreased significantly in all groups, with no group-to-group differences (percent change tibia vBMD high dose vs placebo least-squares means, \u22120.08 [95 CI, \u22120.85 to 0.69] and low dose vs placebo least-squares means, \u22120.22 [95% CI, \u22120.99 to 0.55]). There were no significant treatment effects on any other predefined outcomes. A prespecified sensitivity analysis found a significant interaction between body mass index (BMI) and treatment effect at 2 years. No significant adverse effects were observed.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this randomized clinical trial of 239 early postmenopausal women, supplementation with\n L reuteri<\/jats:italic>\n had no effect on bone loss or bone turnover over 2 years. The observed interaction between BMI and treatment effect warrants further investigation.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04169789<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.15455","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T11:01:07Z","timestamp":1718190067000},"page":"e2415455","source":"Crossref","is-referenced-by-count":39,"title":["Limosilactobacillus reuteri<\/i>\n 6475 and Prevention of Early Postmenopausal Bone Loss"],"prefix":"10.1001","volume":"7","author":[{"given":"Giulia","family":"Gregori","sequence":"first","affiliation":[{"name":"Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Hjertonsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Br\u00e4ttemark","sequence":"additional","affiliation":[{"name":"Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Lorentzon","sequence":"additional","affiliation":[{"name":"Sahlgrenska Osteoporosis Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden"},{"name":"Geriatric Medicine, Sahlgrenska University Hospital, the V\u00e4stra 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