# Efficacy and safety of probiotic/synbiotic supplementation for osteoporosis: a meta-analysis of randomized controlled trials

**Authors:** Xinyu Wang, Lei Zhou, Xingming Yu, Qiang Hou, Chenglong Wang, Wei Cui, Yuheng Hu, Xiumei Wang, Zhuangchen Zhu

PMC · DOI: 10.3389/fmed.2026.1731528 · 2026-02-03

## TL;DR

This study finds that probiotic or synbiotic supplements may safely improve bone density in people with osteoporosis.

## Contribution

A meta-analysis of RCTs shows probiotic/synbiotic supplementation improves lumbar spine BMD and parathyroid hormone levels in osteoporosis patients.

## Key findings

- Probiotic/synbiotic supplementation significantly improved lumbar spine bone mineral density (BMD).
- No increase in adverse events was observed with probiotic/synbiotic use.
- No significant effects were found on total hip BMD or other bone markers like osteocalcin or C-terminal telopeptide.

## Abstract

To evaluate the efficacy and safety of probiotic/synbiotic supplementation for osteoporosis.

PubMed, Embase, Web of Science, and Cochrane databases were used to screen studies up to October 2025. Data pooling used standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). Sensitivity analysis assessed result stability. Review Manager 5.4 and STATA 15.1 were used to analyze. Publication bias was assessed by Egger’s test and funnel plots. Evidence for each outcome was evaluated and graded according to GRADE.

Ten randomized controlled trials (RCTs) with 732 patients were included. Significant improvements in lumbar spine bone mineral density (BMD) (SMD: 0.85; 95% CI: 0.01, 1.69; P = 0.049) and parathyroid hormone (SMD: −1.21; 95% CI: −2.19, −0.23; P = 0.02) existed in the probiotic/synbiotic group. No increase in adverse event risk was observed (RR: 1.03; 95% CI: 0.86, 1.23; P = 0.78). No significant effects were found on total hip BMD, osteocalcin, C-terminal telopeptide, alkaline phosphatase, or osteoprotegerin. No publication bias was detected.

Probiotic/synbiotic supplementation may be safe and effective as an adjunctive treatment for osteoporosis, improving bone density without increasing adverse reactions. Larger, multicenter RCTs are needed to confirm these findings.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024540614, identifier CRD42024540614.

## Linked entities

- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, CYP27A1 (cytochrome P450 family 27 subfamily A member 1) [NCBI Gene 1593] {aka CP27, CTX, CYP27}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}
- **Diseases:** Bone Losses (MESH:D001847), Age-Related Osteoporoses (MESH:D010024), Age (MESH:D019588), venous thromboembolic (MESH:D054556), femoral fractures (MESH:D005264), abdominal distension (MESH:D000007), constipation (MESH:D003248), hepatic coma (MESH:D006501), osteonecrosis of the mandible (MESH:D010020), osteoporotic fracture (MESH:D058866), inflammatory (MESH:D007249), liver disease (MESH:D008107), fracture (MESH:D050723), bone fragility (MESH:C536063), obesity (MESH:D009765)
- **Chemicals:** C-terminal telopeptide (-), denosumab (MESH:D000069448), teriparatide (MESH:D019379), serotonin (MESH:D012701), magnesium (MESH:D008274), bisphosphonates (MESH:D004164), SCFAs (MESH:D005232), calcium (MESH:D002118), vitamin D (MESH:D014807), phosphorus (MESH:D010758), zinc (MESH:D015032), inulin (MESH:D007444)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Lactobacillus gasseri (species) [taxon 1596], Lacticaseibacillus casei (species) [taxon 1582], gut metagenome (species) [taxon 749906], Limosilactobacillus reuteri (species) [taxon 1598], Lactiplantibacillus plantarum (species) [taxon 1590], Bifidobacterium animalis (species) [taxon 28025], Mus musculus (house mouse, species) [taxon 10090], Lacticaseibacillus rhamnosus (species) [taxon 47715], Lacticaseibacillus paracasei (species) [taxon 1597], Lactobacillus acidophilus (species) [taxon 1579]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909203/full.md

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Source: https://tomesphere.com/paper/PMC12909203