Xiong A, Yao Q, He J, Fu W, Yu J, Zhang Z
Geriatric Department of Ningbo First Hospital, 59 Liu-Ting St, Ningbo, 315010, China.
Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Rd, Shanghai, 200233, China.
Osteoporos Int. 2016 Mar;27(3):1031-1039. doi: 10.1007/s00198-015-3341-5. Epub 2015 Nov 20.
We conducted a Mendelian randomization analysis to assess the effect of serum uric acid on bone-related outcomes using a weighted urate transporter genetic risk score as the instrumental variable. The results showed no significance. Our study identified no evidence of a causal role between uric acid and bone-related outcomes.
Observational studies have associated elevated levels of serum uric acid (SUA) with increasing bone mineral density (BMD) and a lowered prevalence of osteoporotic fractures (OFs) in postmenopausal women and elderly men. However, due to unmeasured confounding variables, these observational studies have not provided insight into the causal relationship between SUA and bone-related outcomes. Our aim was to evaluate the effect of SUA on bone-related outcomes using Mendelian randomization.
We recruited 1322 Chinese Han individuals (214 elderly men and 1108 postmenopausal women) from the Shanghai area in China. Mendelian randomization using a two-stage least-squares regression method was conducted with SUA as the exposure variable, a weighted urate transporter genetic risk score as the instrumental variable, and all-site BMD, bone turnover markers, and levels of 25-hydroxyvitamin D3 [25(OH)D], serum calcium (Ca), serum phosphorus (P), and parathyroid hormone (PTH) as outcome variables.
Strong associations between SUA and bone-related outcomes were observed in an ordinary observational analysis (lumbar spine: beta = 0.122, p < 0.0001; hip: beta = 0.104, p < 0.0001; femoral neck: beta = 0.108, p < 0.0001). However, the Mendelian randomization analysis showed no evidence for a causal association of SUA with BMD (lumbar spine: beta = 0.385, p = 0.257; hip: beta = 0.191, p = 0.499; femoral neck: beta = 0.194, p = 0.533). Similar results were found between SUA and other bone-related phenotypes.
Our study identified no evidence of a causal role between SUA and bone-related outcomes, although strong associations in an observational analysis were observed in a population of postmenopausal women and elderly men.
我们进行了一项孟德尔随机化分析，以使用加权尿酸转运体遗传风险评分作为工具变量来评估血清尿酸对骨骼相关结局的影响。结果显示无显著性。我们的研究未发现尿酸与骨骼相关结局之间存在因果关系的证据。
观察性研究表明，绝经后女性和老年男性血清尿酸（SUA）水平升高与骨矿物质密度（BMD）增加以及骨质疏松性骨折（OF）患病率降低有关。然而，由于存在未测量的混杂变量，这些观察性研究并未深入了解SUA与骨骼相关结局之间的因果关系。我们的目的是使用孟德尔随机化来评估SUA对骨骼相关结局的影响。
我们从中国上海地区招募了1322名中国汉族个体（214名老年男性和1108名绝经后女性）。采用两阶段最小二乘回归方法进行孟德尔随机化分析，以SUA作为暴露变量，加权尿酸转运体遗传风险评分作为工具变量，以全身BMD、骨转换标志物以及25-羟基维生素D3 [25(OH)D]、血清钙（Ca）、血清磷（P）和甲状旁腺激素（PTH）水平作为结局变量。
在普通观察性分析中观察到SUA与骨骼相关结局之间存在强关联（腰椎：β = 0.122，p < 0.0001；髋部：β = 0.104，p < 0.0001；股骨颈：β = 0.108，p < 0.0001）。然而，孟德尔随机化分析未发现SUA与BMD之间存在因果关联的证据（腰椎：β = 0.385，p = 0.257；髋部：β = 0.191，p = 0.499；股骨颈：β = 0.194，p = 0.533）。在SUA与其他骨骼相关表型之间也发现了类似结果。
我们的研究未发现SUA与骨骼相关结局之间存在因果关系的证据，尽管在绝经后女性和老年男性人群的观察性分析中观察到了强关联。
