Abstract
BACKGROUND: Osteoporosis is highly prevalent among postmenopausal women and is characterized by a progressive 1-2% annual decline in bone mineral density (BMD). This deterioration contributes to more than 8.9 million fractures globally each year. The condition arises from an imbalance between bone formation and resorption. Emerging evidence suggests that probiotics may positively modulate bone metabolism through gut microbiota regulation, yet high-quality clinical data directly linking probiotic use to bone turnover markers remains limited. This meta-analysis investigates the effects of probiotic supplementation on bone formation and resorption markers in osteoporotic individuals. METHODS: A systematic review and meta-analysis were conducted on 15 randomized controlled trials (RCTs) involving 1,432 participants. The studies assessed various probiotic strains, dosages, and intervention periods ranging from 8 weeks to 12 months. Pooled effect sizes were calculated for key bone formation markers-procollagen type 1 N-terminal propeptide (P1NP) and osteocalcin-and resorption markers, including C-terminal telopeptide of type I collagen (CTX-I), N-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b (TRAP-5b). Subgroup and dose-response analyses were also performed. RESULTS: Probiotic supplementation significantly improved bone metabolism. Bone formation markers showed notable increases, including a significant rise in P1NP (MD = +8.4 μg/L; 95% CI: 3.1-13.7) and osteocalcin. Bone resorption markers, especially CTX-I, demonstrated significant reductions (SMD = -0.35; 95% CI: -0.52 to -0.18). Multi-strain probiotic formulations produced greater improvements in both bone formation and resorption compared with single-strain interventions. A clear dose-response trend was observed, with higher probiotic doses correlating with stronger increases in P1NP. Subgroup analyses showed that postmenopausal women experienced more pronounced benefits than mixed-gender groups. DISCUSSION: Probiotic supplementation is associated with enhanced bone formation and reduced bone resorption in individuals with osteoporosis. Multi-strain formulations and higher dosages yielded the greatest improvements, particularly among postmenopausal women. These findings support probiotics as a promising adjunctive strategy for improving bone health and potentially reducing fracture risk. However, longer-term trials and strain-specific mechanistic studies are needed to confirm clinical utility.