High Phosphate Levels Linked to 78% Higher Fracture Risk in Older Men

Older men with elevated phosphate levels face a 78% increased risk of fractures, according to a new study analyzing nearly 10,000 healthy seniors. This study, a post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, explored the associations between serum phosphate, calcium, and alkaline phosphatase (ALP) levels and fracture risk in older adults. The analysis included 9915 community-dwelling adults aged 70 years and older from Australia, initially free of life-threatening illnesses, with baseline serum measurements and subsequent fracture data collected over a mean follow-up of 3.9 years, during which 907 (9.2%) sustained fractures.

Key findings revealed that men with serum phosphate levels in the highest decile (D10, >1.33 mmol/L) had a significantly increased fracture risk (hazard ratio [HR] = 1.78; 95% confidence interval [CI], 1.25 to 2.54) compared with those in the middle range (D4-D7, 31%-70%). This association persisted after adjusting for multiple confounders, including age, body mass index, smoking, alcohol intake, physical activity, hypertension, diabetes, and estimated glomerular filtration rate (eGFR). However, no such relationship was observed in women (HR = 1.09; 95% CI, 0.83 to 1.44). Notably, serum calcium and ALP levels were not associated with fracture risk in either sex. The results indicate that even within normal phosphate ranges, higher phosphate levels could independently contribute to increased fracture susceptibility in men.

Limitations include the observational nature of the study, the potential variability of non-fasting phosphate measurements, and the inability to isolate specific fracture types, such as hip or vertebral fractures.

“These results provide confirmatory evidence that higher phosphate levels were independently associated with an increased risk of fractures in men,” the study authors concluded. “Further understanding of the mechanism underpinning this relationship could lead to interventions aimed at reducing the population burden of fractures.”

Reference
Hussain SM, Seeman E, Schneider HG, et al. Association of serum phosphate, calcium and alkaline phosphatase with risk of incident fractures in healthy older adults. J Clin Endocrinol Metab. 2024;109(12):e2188-e2195. doi:10.1210/clinem/dgae099