The causal link between osteoarthritis and falls: the mediating role of paracetamol.

backgroundSome observational studies have indicated that osteoarthritis (OA) is a fall risk factor. However, the causal relationship between OA and falls remains unclear.

methodsWe conducted a two-step Mendelian randomization (MR) to investigate the causal relationships between OA, paracetamol use, and the risk of falls and to estimate the mediating effect of paracetamol use. Publicly accessible data for hip OA, knee OA, paracetamol use, and falling risk were sourced from Genome-Wide Association Studies (GWAS).

resultIn the forward MR analysis, the Inverse Variance Weighted (IVW) method indicated that a genetic predisposition to hip OA was significantly associated with an increased risk of falls (OR: 1.053, 95% CI: 1.014 to 1.094, P = 0.007). Consistent directions of effect were observed across other MR analysis methods. The mediated proportion of paracetamol use on the relationship between hip OA and falling risk was 21.70% (β = 0.0113, 95% CI: 5.73-37.8%, P = 0.0078). No causal relationship was observed between knee OA and falling risk, nor between knee OA and the use of paracetamol. In the reversed MR analysis, the IVW method showed that a genetic predisposition to falls may not increase the risk of developing hip and knee OA.

conclusionThese results provide genetic evidence for a causal effect of hip OA on fall risk, partially mediated by paracetamol, and underscore the importance of fall prevention education and cautious paracetamol use for patients with hip OA.