Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean ± SD EPO was 11.5 ± 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function. © 2019 American Society for Bone and Mineral Research.

中文翻译：

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高血浆促红细胞生成素可预测肾功能正常的老年男子的骨折事件：MrOS Sweden队列。

关于促红细胞生成素（EPO）在骨代谢中作用的临床前研究是矛盾的。再生模型表明对骨骼愈合有合成代谢作用，而生理性骨重建模型表明对骨量具有分解代谢作用。没有关于EPO和骨折风险的人类研究。已知成纤维细胞生长因子23（FGF23）影响骨骼矿化，并且估计肾小球滤过率（eGFR）降低的男性中FGF23的血清浓度更高。最近，已经显示了EPO和FGF23之间的直接关联。我们已经探索了人类中EPO与骨矿物质密度（BMD），骨折风险和FGF23之间的潜在关联。分析了999名男性（69至81岁）的血浆EPO水平，参加了MrOS Sweden的基于人群的男性骨质疏松性骨折（MrOS）研究的哥德堡部分。平均±SD EPO为11.5±9.0 IU / L。通过eGFR 60 mL / min对结果进行分层。对于eGFR≥60 mL / min（n = 728）的男性，EPO与年龄（r = 0.13，p <0.001），总髋部BMD（r = 0.14，p <0.001），完整（i）FGF23（r = 0.11，p = 0.004）和骨钙素（r = -0.09，p = 0.022）。全髋关节BMD与EPO之间的关联与年龄，体重指数（BMI），iFGF23和血红蛋白无关（β= 0.019，p <0.001）。在为期10年的随访中，有164例经过X射线验证的骨折，包括117例主要骨质疏松性骨折（MOF），39例髋部骨折和64例椎体骨折。高EPO与发生骨折的风险较高相关（危险比[HR] = 1.43 /每三分之EPO，95％置信区间[CI] 1.35-1.63），MOF（HR = 1.40 /三分之EPO，95％CI 1.08-1.82）和椎体骨折（HR = 1.42 /三分之EPO，95％CI 1.00-2.01）调整后的Cox回归模型。在eGFR <60 mL / min的男性中，未发现EPO与BMD或骨折风险之间存在关联。我们在这里证明，高水平的EPO与肾功能正常的老年男性骨折风险增加和BMD升高有关。©2019美国骨骼和矿物质研究学会。我们在这里证明，高水平的EPO与肾功能正常的老年男性骨折风险增加和BMD升高有关。©2019美国骨骼和矿物质研究学会。我们在这里证明，高水平的EPO与肾功能正常的老年男性骨折风险增加和BMD升高有关。©2019美国骨骼和矿物质研究学会。