LAS VEGAS – A serum uric acid level of 7 mg/dL or more was independently associated with a 62% increased risk of hip fracture among older men participating in the Cardiovascular Health Study.
This finding confirms the clinical relevance of prior translational work pointing to a link between uric acid and bone health, Dr. Tapan Mehta observed at a meeting sponsored by the National Kidney Foundation.
Doug Brunk/Frontline Medicial News
Dr. Tapan Mehta
He and his coinvestigators had suspected the existence of such a link, based upon their prior observations that uric acid inhibits expression of 1-alpha hydroxylase protein in vivo and that elevated uric acid levels are associated with higher parathyroid hormone levels in humans.
A key question now under study in clinical trials is whether lowering uric acid levels in the absence of symptomatic gout provides ancillary benefits to the kidneys.
The Cardiovascular Health Study was a National Heart, Lung, and Blood Institute–funded, population-based, observational study conducted to identify cardiovascular risk factors in men and women aged 65 years and older. In this analysis, Dr. Mehta reported on 1,963 male and 2,729 female participants with baseline serum uric acid levels available.
During a median 11 years of follow-up, 156 first-incident hip fractures occurred. The association between hyperuricemia and increased fracture risk was confined to men, 430 of whom had a baseline serum uric acid of 7 mg/dL or more.
Participants with an elevated uric acid were disproportionately black, obese, in less than good health, and had significantly higher levels of insulin, C-reactive protein, and cystatin C. In a multivariate regression analysis adjusted for demographics, body mass index, alcohol, smoking, physical activity, diabetes, C-reactive protein, hypertension, and known cardiovascular disease, men with a serum uric acid of 7 mg/dL or higher remained at 62% greater risk of hip fracture, compared with those with a uric acid below 7 mg/dL, according to Dr. Mehta of the University of Colorado, Denver.
High uric acid is known to increase the risk of gout, kidney stones, and more rapid progression of chronic kidney disease. It has also been linked to hypertension.
Possible mechanisms that might explain the link between increased serum uric acid and hip fractures include the fact that uric acid suppresses vitamin D activation. Also, uric acid inhibits expression of 1-alpha hydroxylase protein, and higher uric acid levels are associated with higher levels of parathyroid hormone. In addition, uric acid may cause inflammation in bone, which would be expected to increase fragility. But all of these thoughts on mechanism remain speculative for now, according to the nephrologist.
The absence of a relationship between hyperuricemia and hip fractures in older women in the Cardiovascular Health Study suggests other factors are more important than uric acid levels in women.
Dr. Mehta reported having no financial conflicts regarding this study.