Does osteosarcopenia synergistically increase risk for incident falls and fractures? A systematic review and meta-analysis

It is unclear whether comorbid low bone mineral density (BMD) and sarcopenia, known as 'osteosarcopenia', synergistically increase fall and fracture risk. This review aims to determine whether osteosarcopenia confers a greater risk for incident falls and fractures than low BMD or sarcopenia alone. Relevant databases were searched from inception to 2025 for prospective studies in populations aged ≥ 50 years comparing fall and fracture risk in osteosarcopenia to low BMD (T-Score < -1.0) or sarcopenia alone. Meta-analyses calculated risk ratios (RR) and measures of interaction on additive (relative excess risk due to interaction; RERI) and multiplicative (multiplicative interaction ratio; MR) scales. Seven records (n = 813) were included. Osteosarcopenia was associated with similar fracture risk as low BMD (RR 1.22; 95% CI 0.96, 1.56; k = 6, I² = 0%), but higher risk than sarcopenia (RR 2.12; 95% CI 1.42, 3.15; k = 5; I² = 0%). Falls risk did not differ for osteosarcopenia compared to low BMD (RR 1.15; 95% CI 0.44, 2.97; k = 3; I² = 72.9%) or sarcopenia (RR 1.06; 95% CI 0.70, 1.59; k = 3; I² = 1.1%). Synergy analyses showed pooled RERI of 0.35 (95% CI - 0.22, 0.91; k = 5) for fractures and - 0.16 (95% CI - 0.60, 0.28; k = 3) for falls, with MR estimates of 1.21 (95% CI 0.90 to 1.62) and 0.83 (95% CI, 0.64 to 1.09), respectively. Risk of incident fracture in osteosarcopenia is similar to that of low BMD, but higher than sarcopenia, and falls risk does not differ between conditions. The absence of significant additive or multiplicative interactions suggests there is insufficient evidence to support the promotion of osteosarcopenia as a distinct diagnostic entity.