J Health Popul Nutr. 2026 Feb 4. doi: 10.1186/s41043-025-01219-0. Online ahead of print.
ABSTRACT
BACKGROUND: This study aimed to clarify 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 through 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, serum calcium concentration showed an inverse linear association with all-cause and CVD mortality. Although smoothed curve fitting visually suggested U-shaped and L-shaped patterns for all-cause and CVD mortality, respectively, formal tests for nonlinearity did not reach statistical significance (P for log-likelihood ratio > 0.05). Specifically, the risk was elevated at lower calcium levels and stabilized or showed a non-significant increase at higher levels. In the piecewise linear model, serum calcium below 9.50 mg/dL was inversely associated with all-cause mortality, where each 1 mg/dL increase was associated with a 48% lower risk (HR 0.52, 95% CI: 0.30-0.91). Above 9.50 mg/dL, the association was non-significant (HR 1.09, 95% CI: 0.51-2.35). A similar L-shaped pattern was observed for CVD mortality below the inflection point (HR 0.26, 95% CI: 0.09-0.74). However, formal likelihood ratio tests comparing the threshold model with a linear model did not reach statistical significance (P > 0.05), indicating that the data do not provide strong evidence against a linear association.
CONCLUSION: Our primary analysis supports an inverse linear association between serum calcium and mortality in OA patients. Although exploratory analyses revealed potential non-linear patterns visually, these were not statistically confirmed. Therefore, the overall relationship is best characterized as linear within the observed range, with lower serum calcium associated with higher mortality risk. Therefore, these findings highlight a potential optimal range for serum calcium but require verification in future studies designed to confirm nonlinearity and assess the clinical utility of calcium management.
PMID:41639742 | DOI:10.1186/s41043-025-01219-0
