Kidney stone formers at high risk of fracture

Kidney stone formers may be at elevated risk for fracture, according to a new study.

Using The Health Improvement Network database, Michelle R. Denburg, MD, of the Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues studied a retrospective cohort of 51,785 individuals with urolithiasis and 517,267randomly selected age-, sex-, and practice-matched matched subjects.

Over a median observation period for ascertainment of incident fracture of 4.7 years in both groups, 3,524 incident fractures (118 per 10,000 person-years) occurred in participants with urolithiasis compared with 29,590 in those without urolithiasis (101 per 10,000 person-years), the researchers reported online ahead of print in the Clinical Journal of the American Society of Nephrology.

Among subjects with urolithiasis, the median time from diagnosis to fracture was 10 years.

Among male participants, urolithiasis was associated with a significant 13% overall increased risk of fracture. The risk of fracture associated with urolithiasis was significantly elevated among those aged 10–19 years (55% higher), 40–49 years (17% higher), 50–59 years (20% higher), and 80–89 years (25% higher). Among female participants, the fracture risk associated with urolithiasis was significantly elevated among those aged 30–39 years (55% higher), 40–49 years  (45% higher), 50–59 years (32% higher), 60–69 years (25% higher), and 70–79 years (21% higher).

“Given that the time from initial diagnosis of urolithiasis to first fracture was a decade and that the excess risk affected all skeletal sites, there is reason to believe that we might possibly be able to intervene during this critical interval and decrease the risk of future fracture,” Dr. Denburg's group concluded.

The researchers stated that their study cannot establish a causal mechanism, but it confirms the association between urolithiasis and risk of subsequent fracture. A previous retrospective study of 624 patients with symptomatic urolithiasis published in Kidney International (1998;53:459–464) of 624 demonstrated a 4-fold increased risk of a first vertebral fracture than expected in the general population.

A subsequent cross-sectional study of 793 participants in the Third National Health and Nutrition Examination Survey showed that men, but not women, who reported a history of renal calculi were more likely to report a history of spine and wrist fractures, according to findings published in the Journal of Bone and Mineral Research (2001;16:1893–1898).

Dr. Denburg and her collaborators noted that current evidence points to an association between idiopathic hypercalciuria (IH) and diminished bone mineral density (BMD).

Previous studies have shown that IH in childhood is associated with low BMD, “suggesting that life-long hypercalciuria may compromise bone health and increase fracture risk.” Studies of post-menopausal women with primary osteoporosis have documented a 10%–19% prevalence of hypercalciuria, the researchers pointed out.