Introduction: At present, clinical studies have confirmed that osteoporosis (OP) has an inverse relationship with osteoarthritis (OA), but it has not been proven from the point of view of genetics, so our study hopes to clarify the potential effect of OP on OA at the level of gene prediction through two-sample Mendelian randomization (MR) analysis.

Methods: A two-sample MR was adopted to research the causal relationship of OP with OA (including total OA, knee OA and hip OA). All data come from a public shared database. Such traditional methods as simple and weighted models, inverse variance weighted, weighted median, and Mendelian Randomization (MR-Egger) regression were employed to assess the causal effect of OP on OA. We used the Pleiotrophy RESidual Sum and Outlier (MR-PRESSO) method and MR-Egger method to study sensitivity. The leave-one-out test is used to determine the influence of outliers. The heterogeneity was calculated by using Cochran Q statistics and MR-Egger regression in the inverse variance-weighted (IVW) method. P > 0.05 indicates that there is a large heterogeneity. MR-Robust Adjustment Profile Score (RAPS) is stable to both systematic and specific multiplicity, so we used MR-RAPS as a supplementary method to verify the results of IVW.

Results: According to the results of IVW, we found that there was a causal relationship between OP and total OA, and OP reduced the incidence of total OA (beta=-0.285, OR=0.751, P value< 0.016). The MR estimation of the causal effect of OP on knee OA suggested that the genetic prediction of OP was negatively correlated with knee osteoarthritis (KOA) (IVW: beta=-6.11, OR=0.002, P value< 0.016). The IVW results suggested that OP was causally related to hip OA, and OP had a protective effect on hip OA (beta=-5.48, OR=4.15e-3, P value= 3.99e-3). Except for heterogeneity in the analysis of OP and knee OA, there was no horizontal pleiotropy or heterogeneity in the other analyses.

Conclusion: We explored the causal relationship between OP and OA through a two-sample MR analysis and found that OP can reduce the incidence of OA (including knee OA and hip OA).