Association of Serum Phosphate, Calcium and Alkaline Phosphatase With Risk of Incident Fractures in Healthy Older Adults

Context: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling. Objective: We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals. Methods: A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and ALP measurement. Fracture data were collected post randomization. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. Phosphate, Ca, and ALP were analyzed in deciles (D1-D10), with deciles 4 to 7 (31%-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations. Results: Of the 9915 participants, 907 (9.2%) individuals had incident fractures recorded over 3.9 (SD 1.4) years. In the fully adjusted model, men in the top decile (D10) of phosphate had a 78% higher risk of incident fracture (HR 1.78; 95% CI, 1.25-2.54). No such association was observed for women (HR 1.09; 95% CI, 0.83-1.44). The population attributable fraction in men within the D10 phosphate category is 6.9%. Conclusion: This result confirms that high-normal serum phosphate levels are associated with increased fracture risk in older men.