Effects of 12-Month Probiotic Supplementation on Bone Mineral Density and Bone Turnover Markers in Early Postmenopausal Females: A Double-Blind Randomized Controlled Trial

Background Early postmenopausal females experience rapid bone loss, and modulation of the gut–bone axis has been proposed as a preventive strategy. However, the role of probiotics relative to established lifestyle factors such as nutrition and physical activity remains unclear. Objectives To evaluate whether 12 months of supplementation with a lactobacilli-based probiotic attenuates bone loss in early postmenopausal females. Methods In this double-blind, randomized, placebo-controlled trial, 114 females 1–8 years postmenopause were allocated to a daily probiotic ( Lactiplantibacillus plantarum DSM15312, DSM15313, and Lacticaseibacillus paracasei DSM13434) or placebo. The primary outcome was change in distal tibia total volumetric bone mineral density (vBMD) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondary outcomes included additional HR-pQCT parameters, areal BMD (aBMD) by DXA, and circulating biomarkers. Intention-to-treat analyses were conducted using linear mixed-effects models, adjusted for baseline covariates; secondary outcomes were corrected for multiple comparisons. Results A total of 114 participants were randomized, and all available data were included in the analyses. Baseline characteristics were broadly comparable. Over 12 months, both groups experienced modest declines in bone density. The primary analysis showed a modest but statistically significant greater decline in distal tibia total vBMD in the probiotic group compared with placebo (−3.7 mg HA/cm 3 ; 95% CI: −6.9, −0.4; p = 0.027). Similar trends were observed at other peripheral sites, but most secondary outcomes were not significant after multiple testing correction. No treatment effects were observed for bone turnover, calciotropic, or inflammatory markers. Conclusions In early postmenopausal females, 12-month supplementation with a lactobacilli-based probiotic did not attenuate bone loss and was associated with a small but statistically significant greater reduction at the primary site. These findings do not support this probiotic formulation as a standalone intervention for skeletal preservation. Clinical trial registration number ACTRN12621000810819 URL of registration https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381292&isReview=true