Gout and Risk of Fracture in Women: A Prospective Cohort Study

Abstract

Objective Uric acid may be linked to bone health through its anti-oxidant or pro-oxidant effects, thereby affecting bone resorption and formation, or through inhibition of vitamin D activation and higher parathyroid hormone level. Prior studies on the relation between uric acid and bone mineral density have demonstrated conflicting results. To date, there are no prospective studies examining the relation between gout, a disease characterized by hyperuricemia and inflammation, and hip or wrist fracture risk in women. Methods We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses’ Health Study (n=103,799 at baseline with 14 years of follow-up for the wrist fracture analysis and 22 years of follow-up for the hip fracture analysis). Gout history and wrist and hip fracture were assessed by biennial questionnaires. Cox proportional-hazards models were used to simultaneously adjust for potential confounders. Results There were 3,769 incident wrist fractures (1990–2004) and 2,147 incident hip fractures (1990–2012), with 107 wrist and 117 hip fractures among participants with gout. The multivariable-adjusted relative risk of wrist fracture in women with a history of gout compared with women without gout was 1.12 (95% CI 0.92 to 1.36). The multivariable-adjusted relative risk of hip fracture in women with a history of gout compared with women without gout was 1.38 (95% CI 1.14 to 1.68). Conclusion A history of gout is associated with a modestly increased risk of hip fracture but not significantly associated with risk of wrist fracture in women.

Gout is not associated with the risk of fracture: a meta-analysis

“…Tzeng et al [23] reported that gout history increased the fracture risk, which was consistent with the results of a Chinese adult-based research conducted by Wang et al [24]. However, the relationship became variable when focus on different fracture sites in the study performed by Paik et al [17], in which the risk of fractures raised in the hip but not in the wrist. Kim et al [25] conducted a large-scale epidemiological study and demonstrated the neutral association between gout and bone health, and Sultan et al [1] reported the similar results in a nationally representative cohort research.…”

“…After 326 studies excluded by duplicates, 2291 excluded by reading titles and abstracts, and 32 studies were downloaded and carefully checked by reading full texts. After careful reading, five articles [1, 17, 23–25] involving eight datasets were considered to be qualified for the quantitative analysis of the association of gout with the risk of fractures, and four articles [1, 23, 26, 28] were considered to be qualified for the quantitative analysis of the association of urate-lowering with the risk of fractures. The inclusion processes and reasons for exclusion were depicted in Fig.…”

“…With regard to the data source, all seven studies [1, 17, 23–26, 28] involved in the participants from the different data source. As for study type, five described retrospective cohort studies [1, 23–26] and two prospective cohort study [17, 28]. Kim et al and Paik et al [17, 25] presented data about the association between gout and fracture risk in two different cohorts based on the fracture localizations.…”

“…However, the increased serum level of uric acid (UA) in gout [15], which is the degradation production of purine compounds [16], made the relationship inconsistent. UA may affect bone health, including resorption and formation, through its two-way control of oxidative stress due to its antioxidant or pro-oxidant properties [17], and several prior studies on the association between hyperuricemia and bone mineral density (BMD) also demonstrated conflicting results [18–22]. Meanwhile, the urate-lowering therapy faced a dilemma when considering the relationship with fracture.…”

Risk of fragility fracture among patients with gout and the effect of urate-lowering therapy

“…6-8 A US-based study 21 reported positive associations between gout and incidence of hip and wrist fracture in women, with an adjusted excess risk of 12% and 38%, respectively. Although this study refutes our findings, it used self-reported information on both gout and fracture, which may have introduced bias.…”