Dietary Supplements

Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis.

TL;DR

Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis, with multi-strain formulations and higher dosages yielding the greatest improvements, particularly among postmenopausal women.

Key Findings

Probiotic supplementation significantly increased the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in osteoporotic individuals.

  • Pooled mean difference for P1NP was MD = +8.4 μg/L (95% CI: 3.1–13.7).
  • The analysis was based on 15 RCTs involving 1,432 participants.
  • Intervention periods ranged from 8 weeks to 12 months.
  • A clear dose-response trend was observed, with higher probiotic doses correlating with stronger increases in P1NP.

Probiotic supplementation significantly reduced the bone resorption marker C-terminal telopeptide of type I collagen (CTX-I).

  • Pooled standardized mean difference for CTX-I was SMD = -0.35 (95% CI: -0.52 to -0.18).
  • Other resorption markers assessed included N-terminal telopeptide (NTX) and tartrate-resistant acid phosphatase 5b (TRAP-5b).
  • The meta-analysis covered 15 RCTs with 1,432 total participants.
  • Various probiotic strains and dosages were assessed across included studies.

Probiotic supplementation significantly increased the bone formation marker osteocalcin in osteoporotic individuals.

  • Osteocalcin was assessed as a key bone formation marker alongside P1NP.
  • The finding was based on pooled effect sizes calculated across 15 RCTs.
  • Studies included various probiotic strains, dosages, and intervention periods ranging from 8 weeks to 12 months.
  • Specific pooled effect size values for osteocalcin were not separately reported in the abstract.

Multi-strain probiotic formulations produced greater improvements in both bone formation and resorption markers compared with single-strain interventions.

  • Subgroup analyses comparing multi-strain versus single-strain formulations were performed.
  • Greater improvements were observed for both formation markers (P1NP and osteocalcin) and resorption markers (including CTX-I).
  • This finding emerged from subgroup analysis within the 15-RCT, 1,432-participant dataset.
  • The result supports multi-strain formulations as potentially superior for bone health outcomes.

Postmenopausal women experienced more pronounced benefits from probiotic supplementation than mixed-gender groups.

  • Subgroup analyses stratified results by population type, including postmenopausal women versus mixed-gender groups.
  • The greater effect in postmenopausal women was observed across bone turnover markers.
  • Osteoporosis is described as highly prevalent among postmenopausal women and characterized by a progressive 1–2% annual decline in bone mineral density (BMD).
  • This finding suggests that postmenopausal women may represent the population most likely to benefit from probiotic supplementation.

A dose-response relationship was identified between probiotic dosage and improvements in bone formation markers.

  • Higher probiotic doses correlated with stronger increases in P1NP.
  • Dose-response analyses were conducted as part of the subgroup and supplementary analyses.
  • Various dosages were compared across the 15 included RCTs.
  • The dose-response trend was described as 'clear' in the abstract.

The meta-analysis included 15 randomized controlled trials involving 1,432 participants assessing multiple probiotic strains, dosages, and intervention durations.

  • Intervention periods ranged from 8 weeks to 12 months.
  • Bone formation markers assessed were P1NP and osteocalcin; resorption markers were CTX-I, NTX, and TRAP-5b.
  • Pooled effect sizes were calculated using mean difference (MD) and standardized mean difference (SMD) depending on the outcome.
  • Subgroup and dose-response analyses were also performed.

Have a question about this study?

Citation

Yuan Y, Li J, Wang K, Li J, Wei H. (2026). Meta-analysis of the effects of probiotic supplementation on bone turnover markers in middle-aged and elderly patients with osteoporosis.. Frontiers in cellular and infection microbiology. https://doi.org/10.3389/fcimb.2025.1738378