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 mo 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 to 8 y 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 (BMD) assessed by high-resolution peripheral quantitative computed tomography. Secondary outcomes included additional high-resolution peripheral quantitative computed tomography parameters, areal BMD by dual-energy X-ray absorptiometry, 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 randomly assigned, and all available data were included in the analyses. Baseline characteristics were broadly comparable. Over 12 mo, both groups experienced modest declines in bone density. The primary analysis showed a modest but statistically significant greater decline in distal tibia total volumetric BMD in the probiotic group compared with placebo (-3.7 mg HA/cm3; 95% confidence interval: -6.9, -0.4 mg HA/cm3; 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-mo supplementation with a lactobacilli-based probiotic does 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. This trial was registered at the Australian and New Zealand Clinical Trials Registry as ACTRN12621000810819.