U-Shaped Association of Serum Calcium Concentration with All-Cause Mortality and L- Shaped Association with Cardiovascular Mortality in Patients with Osteoarthritis: A Retrospective Cohort Study

Abstract Background: To clarify the nonlinear relationship between serum calcium and mortality in osteoarthritis (OA) patients using NHANES data (2003–2018). Method: A total of 1,249 adults with OA were included. Mortality outcomes were ascertained via linkage to the National Death Index (NDI). Cox proportional hazards models were used to assess the independent association of serum calcium concentration with the risk of death. We used a two-stage Cox proportional hazards model to elucidate the nonlinear relationship between serum calcium concentration and the risk of death in patients with OA. Stratified analyses were performed to identify patients at higher risk. Results: During follow-up (median: 9.7 years), 220 all-cause deaths occurred (56 CVD-related, 64 cancer-related). After adjusting for relevant variables, it was found that there was a clear nonlinear relationship between higher serum calcium concentration and higher risk of all-cause and CVD mortality in OA participants. In addition, we found a U-shaped association between serum calcium level and all-cause mortality (crossing point: 9.50 mg/dL, HR = 0.52, 95%CI: 0.30–0.91 in the low calcium group; HR = 1.09, 95%CI: 0.51–2.35), and showed an L-shaped association with CVD mortality (inflamation point: 9.50 mg/dL, HR = 0.26, 95%CI: 0.09–0.74). Conclusion: Serum calcium exhibits nonlinear associations with all-cause and CVD mortality in OA patients, suggesting optimal levels near 9.50 mg/dL. It is determined that appropriate reduction of serum calcium level is beneficial to the physical health of OA patients, but further clinical effects need to be verified by large clinical trials.