Strain-specific and dose-dependent clinical efficacy of probiotics on bone mineral density improvement in postmenopausal women: a meta-analysis based on RCT studies.

BACKGROUND

Probiotics may provide a safe and feasible alternative or adjuvant strategy for osteoporosis. However, there is no consensus on its strain specificity, dose threshold, and site differences. This meta-analysis quantitatively evaluates the strain-specific and dose-dependent clinical efficacy of probiotics on bone mineral density (BMD) in postmenopausal women.

METHODS

Systematically search PubMed, Embase, Web of Science Core Collection, Scopus, Cochrane, and ClinicalTrials.gov up to December 24, 2025. Randomized controlled trials (RCTs) of probiotic/synbiotic interventions in postmenopausal women were included. A fixed-effects model was used to pool the standardized mean differences (SMD). Subgroup analyses were conducted based on probiotic genus (with Lactobacillus vs. without Lactobacillus), strain number (single vs. multi-strain), dose (≥ 1 × 10¹⁰ vs. <1 × 10¹⁰ CFU/d), and intervention duration.

RESULTS

A total of 11 RCTs (12 reports, n = 1388) were entered into the analysis. Overall change in BMD was not significant (SMD = 0.01, 95% CI = -0.06, 0.08, I² = 0%). Lumber spine BMD was significantly higher in Lactobacillus subgroup (SMD = 0.19, 95% CI = 0.01, 0.37). Lactobacillus showed negative trends in hip (SMD = -0.07) and femur (SMD = -0.08) BMD. Exploratory analyses suggested a potential dose-response plateau at 1 × 10⁹-7.5 × 10⁹ CFU/d. Prolonged interventions (> 6 months) or higher dose did not increase lumbar gains and conversely turned the hip/femur effect negative. Safety profile did not differ from placebo. Based on the GRADE framework, evidence was moderate for lumbar spine BMD and adverse events but low for hip and femur BMD. This means research is needed to refine these estimates.

CONCLUSIONS

Effect of probiotics on BMD in postmenopausal women is site-genus-dose dependent. A single Lactobacillus strain at 1 × 10⁹-7.5 × 10⁹ CFU/d for 3-6 months is recommended for lumbar spine protection.

CLINICAL TRIAL NUMBER: Not applicable.