骨转换生物标志物可识别出具有更高骨折风险的慢性肾脏病患者亚组。
Biomarkers of Bone Turnover Identify Subsets of Chronic Kidney Disease Patients at Higher Risk for Fracture.
机构信息
Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, California.
Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
出版信息
J Clin Endocrinol Metab. 2020 Aug 1;105(8):e2903-11. doi: 10.1210/clinem/dgaa317.
BACKGROUND
We sought to identify biomarkers that indicate low turnover on bone histomorphometry in chronic kidney disease (CKD) patients, and subsequently determined whether this panel identified differential risk for fractures in community-dwelling older adults.
METHODS
Among CKD patients who underwent iliac crest bone biopsies and histomorphometry, we evaluated candidate biomarkers to differentiate low turnover from other bone disease. We applied this biomarker panel to 641 participants in the Health Aging and Body Composition Study (Health ABC) study with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 who were followed for fracture. Cox proportional hazards models evaluated the association of bone mineral density (BMD) with fracture risk and determined whether biomarker-defined low bone turnover modified fracture risk at any level of BMD.
RESULTS
In 39 CKD patients age 64 ± 13 years, 85% female, with mean eGFR 37 ± 14 mL/min/1.73 m2 who underwent bone biopsy, lower fibroblast growth factor (FGF)-23, higher ɑ-Klotho, and lower parathyroid hormone (PTH) indicated low bone turnover in accordance with bone histomorphometry parameters (individual area under the curve = 0.62, 0.73, and 0.55 respectively; sensitivity = 22%, specificity = 100%). In Health ABC, 641 participants with CKD were age 75 ± 3 years , 49% female, with mean eGFR 48 ± 10 mL/min/1.73 m2. For every SD lower hip BMD at baseline, there was an 8-fold higher fracture risk in individuals with biomarker-defined low turnover (hazard ratio 8.10 [95% CI, 3.40-19.30]) vs a 2-fold higher risk in the remaining individuals (hazard ratio 2.28 [95% CI, 1.69-3.08]) (Pinteraction = .082).
CONCLUSIONS
In CKD patients who underwent bone biopsy, lower FGF-23, higher ɑ-Klotho, and lower PTH together had high specificity for identifying low bone turnover. When applied to older individuals with CKD, BMD was more strongly associated with fracture risk in those with biomarker-defined low turnover.
背景
我们试图确定能指示慢性肾脏病（CKD）患者骨组织形态计量学中低转换的生物标志物，并随后确定该标志物是否能识别社区居住的老年人群中骨折的不同风险。
方法
我们评估了 CKD 患者中接受髂嵴骨活检和骨组织形态计量学的候选生物标志物，以区分低转换和其他骨骼疾病。我们将该生物标志物应用于肾小球滤过率（eGFR）<60ml/min/1.73m2 的健康老龄化和身体成分研究（Health ABC）中 641 名参与者，这些参与者接受了随访以评估骨折情况。Cox 比例风险模型评估了骨密度（BMD）与骨折风险的相关性，并确定在任何 BMD 水平下，生物标志物定义的低骨转换是否改变了骨折风险。
结果
在 39 名年龄 64±13 岁、85%为女性、平均 eGFR 为 37±14ml/min/1.73m2 的 CKD 患者中，较低的成纤维细胞生长因子（FGF）-23、较高的 α-Klotho 和较低的甲状旁腺激素（PTH）与骨组织形态计量学参数一致，表明低骨转换（个体曲线下面积分别为 0.62、0.73 和 0.55；灵敏度分别为 22%、100%）。在 Health ABC 中，641 名 CKD 参与者的年龄为 75±3 岁，49%为女性，平均 eGFR 为 48±10ml/min/1.73m2。在基线时，髋部 BMD 每降低一个标准差，生物标志物定义的低转换个体的骨折风险增加 8 倍（风险比 8.10[95%CI，3.40-19.30]），而其余个体的骨折风险增加 2 倍（风险比 2.28[95%CI，1.69-3.08]）（P 交互值为 0.082）。
结论
在接受骨活检的 CKD 患者中，较低的 FGF-23、较高的 α-Klotho 和较低的 PTH 联合使用具有很高的特异性，可以识别低骨转换。当将其应用于患有 CKD 的老年个体时，与生物标志物定义的低转换个体相比，BMD 与骨折风险的相关性更强。
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