Relationships between serum uric acid concentrations, uric acid lowering medications, and vertebral fracture in community-dwelling elderly Japanese men: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study

Abstract

Purpose: The association between serum concentrations of uric acid (UA), a potent endogenous antioxidant, and fracture risk has not yet been examined for morphometric vertebral fracture (VF). This study aimed to determine whether serum UA concentrations are associated with risks of clinical osteoporotic fracture (OPF) and morphometric VF after adjusting for confounding factors including UA-lowering medications (ULMs).

Materials and methods: A total of 2012 Japanese men aged ≥65 years completed the baseline study, which included serum UA measurement and X-ray absorptiometry-based VF assessment. We conducted a follow-up study five years later to identify incident OPFs and VFs. OPF was identified through interviews. Incident VF was defined as a vertebra which showed reduction in any of its anterior, central, or posterior heights by ≥20% during follow-up, and satisfied grade one or higher fracture criteria in Genant's method on follow-up images. Bone mineral density (BMD) of the hip and spine was measured by dual-energy X-ray absorptiometry at baseline and follow-up.

Results: We identified 45 clinical OPFs from 2000 men and 39 VFs from 1530 men during a mean follow-up period of 4.3 years. Hip BMD was significantly higher in higher UA concentration groups after adjusting for age and body mass index. A significantly decreased multivariate-adjusted odds ratio (OR) of incident VF was observed for the highest quartile groups of serum UA concentrations compared with the lowest quartile group (OR: 0.17, 95% confidence interval: 0.05-0.62). This OR remained significant after further adjusting for ULM use. ULM users in the lowest quartile group of serum UA concentrations had a significantly higher incidence rate of VF compared to the other quartile groups.

Conclusions: Higher serum UA concentrations were associated with a lower risk of morphometric VF independently of ULM in Japanese elderly men. Excessive reduction of serum UA concentrations by ULM might increase VF risk.

Keywords: Gout; Morphometric vertebral fracture; Osteoporotic fracture; Population-based prospective cohort study; Serum uric acid concentration; Uric acid lowering medication.