Lowering serum urate with urate-lowering therapy to target and incident fracture among people with gout.

Abstract

Gout is associated with a higher risk of fracture; however, the associations of hyperuricemia and urate-lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 μmol/L) reduces risk of fracture among people with gout. We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a United Kingdom primary care database. Individuals with gout who were 40 years or older and initiated ULT were included in the study. Among 28,554 people with gout, the 5-year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for "not achieving the target SU level" arm, respectively. The risk difference and hazard ratio for "achieving the target SU level" arm was -0.3% (95% confidence interval [CI]: -0.5% to -0.1%) and 0.66 (95% CI: 0.46 to 0.93), respectively, compared with "not achieving the target SU level". Similar results were observed when the associations of lowering SU level with ULT to the target levels with the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and non-vertebral fracture were assessed. In this population-based study, lowering the SU level with ULT to the guideline-based target level is associated with a lower risk of incident fracture in people with gout.