Fracture Risk Linked to Elevated Phosphate Levels Among Older Men – Renal and Urology News

High-normal serum phosphate levels are a risk factor for fracture risk among older men, according to study findings published in the Journal of Clinical Endocrinology & Metabolism.

Aging is associated with unbalanced bone remodeling, which causes resorption of calcium and phosphate from bone. Although circulating levels of calcium and phosphate may be markers for fracture risk, previous study findings have not established significant relationships between circulating minerals and bone fragility.

To evaluate the associations between phosphate and fractures among older individuals, researchers from Monash University in Australia sourced data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which included adults aged 70 years and older living in Australia (n=16,703) and adults aged 65 years and older living in the United States (n=2411) between 2010 and 2014. Participants without cardiovascular disease, dementia, physical disability, or chronic illness were randomized to receive aspirin 100 mg daily or placebo.

In this post-hoc analysis of ASPREE, the researchers compared risk for incident fracture with serum calcium, phosphate, and alkaline phosphatase (ALP) levels among a subset of participants with sufficient data (n=9915).

The participants had a mean age of 74.9 years (SD, 4.0) and a mean body mass index (BMI) of 28.0 kg/m² (SD, 4.4). Among the participants, 49.8% were women, 64.9% engaged in moderate to high physical activity, 73.8% had hypertension, and 65.7% had dyslipidemia.

Men and women had average calcium levels of 2.35 (SD, 0.10) and 2.37 (SD, 0.11) mmol/L, phosphate levels of 1.06 (SD, 0.15) and 1.19 (SD, 0.15) mmol/L, and ALP levels of 77.1 (SD, 23.0) and 80.9 (SD, 22.0) U/L, respectively.

During a mean follow-up of 3.9 years, the incident fracture rate was 9.2%.

The researchers observed significant gender interactions between fracture risk and serum phosphate levels (P =.04) but not serum calcium (P =.079) or ALP (P =.98) levels.

Stratified by serum phosphate, the risk for incident fracture increased with serum phosphate levels among men. The risk increased from 110 per 10,000 person-years (py) to 243 per 10,000 py among men with serum phosphate levels in the first vs tenth deciles. Compared with individuals in the fourth to seventh decile of serum phosphate levels, men in the tenth serum phosphate decile had an increased fracture risk (adjusted hazard ratio [aHR], 1.78; 95% CI, 1.25-2.54).

Among women, the researchers identified no trend between fracture risk and phosphate levels.

The trend of significant fracture risk among men in the tenth decile of serum phosphate levels remained significant when excluding:

• Individuals with incident cancer (aHR, 3.51; 95% CI, 1.90-6.50);
• Individuals with incident major adverse cardiac events (aHR, 2.72; 95% CI, 1.52-4.85);
• Individuals with chronic kidney disease (aHR, 1.97; 95% CI, 1.36-2.84); and,
• Individuals who reported heavy alcohol drinking (aHR, 1.70; 95% CI, 1.17-2.44).

Study limitations include the exclusion of any hip- or vertebral-specific fracture analyses and the exclusion of participants with abnormal liver function test results.

The researchers concluded, “These results provide confirmatory evidence that higher phosphate levels were independently associated with an increased risk of fractures in men as previously reported from the Rotterdam and the [Osteoporotic Fractures in Men] study.”

This article originally appeared on Endocrinology Advisor