Stones and Fractures: Making a Connection

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Nephrology Update

People with urolithiasis — especially male teens and young women — are at a higher risk for bone fractures than the general population, according to a study from nephrologists at The Children’s Hospital of Philadelphia that was published in the Clinical Journal of the American Society of Nephrology.

“We wanted to look across the lifespan to see how stones affected bone health, and we found compelling evidence of an association with increased risk of fractures,” says Michelle Denburg, MD, MSCE, lead author. For the population-based retrospective cohort study, Denburg and her colleagues used The Health Improvement Network (THIN) database and analyzed electronic health record data on 51,785 people in the United Kingdom who were diagnosed with urolithiasis and 517,267 matched individuals without urolithiasis.

According to Denburg, the THIN database has the advantage of drawing from 10 million people followed by primary care physicians in the UK National Health Service.

Having a kidney stone was significantly linked with fractures. In males, there was an overall 10 percent greater risk in those with urolithiasis, and the risk was greatest in adolescence (55 percent higher). In females, there was a 17-25 percent higher risk of fracture in women 30-79 years old, with the highest risk in those 30-39 years old. Even when adjusting for potential confounding conditions and medications, the association between urolithiasis and fracture remained significant.

Individuals with limited mobility or who only had codes for renal colic, bladder/lower urinary tract calculi (presumed infectious), infectious calculi, hypercalciuria, or nephrocalcinosis were excluded from the entire cohort.

For those with urolithiasis, the median time between the first diagnosis of stones and the first fracture was 10 years. The most common fracture site for men was the hands, and for women was the forearm/wrist. There was no difference for either men or women in the distribution of fracture sites between the groups with and without stones.

Given the well-documented growth in the incidence of urolithiasis, this study points out profound implications for patient outcomes and healthcare costs in the future. It also opens up new questions.

“Given that the median time from diagnosis of urolithiasis to fracture was a decade, we might be able to intervene during this interval to reduce the burden of future fracture,” Denburg says. “The THIN database does not have full metabolic profiles of urine, but it is worth trying to ascertain if there is an underlying metabolic abnormality that we could treat to prevent negative long-term outcomes. Are fractures the result of a cumulative burden of hypercalciuria over a person’s lifetime?”

Denburg and senior author Lawrence Copelovitch, MD, are currently studying whether specific treatments for urolithiasis correlate with outcomes such as hypertension and chronic kidney disease.