Markers of Bone Turnover in Gaucher Disease: Modeling the Evolution of Bone Disease
Markers of Bone Turnover in Gaucher Disease: Modeling the Evolution of Bone Disease
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DOI：
10.1210/jc.2011-0162
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
Hollak, C. E. M.
中科院分区：
文献类型：
--
作者：
van Dussen, L.;Lips, P.;Hollak, C. E. M.
背景：戈谢病（GD）是一种以大量巨噬细胞存在为特征的溶酶体贮积症。骨并发症和低骨密度被认为是由巨噬细胞衍生因子介导的骨吸收增强引起的。目的：本研究的目的是调查骨转换和骨并发症之间的关系。设计：这是一项回顾性队列研究和文献回顾。患者：40例成人I型GD患者被纳入本研究。结果测量：骨吸收标记物1型胶原C末端肽和两种骨形成标记物1型前胶原N末端前肽和骨钙素的水平与临床骨疾病、总体疾病严重程度的测量和代表骨髓浸润的成像数据的关系进行了研究。50%的患者骨钙素降低（中位数0.35 nmol/L，正常值0.4-4.0），表明骨形成减少。1型胶原C端肽和1型前胶原N端前肽在大多数患者的正常范围内。骨钙素浓度与总体疾病严重程度呈负相关，与成像数据呈正相关（相关系数0.423; P = 0.025），表明与疾病严重程度有关。文献综述显示，骨吸收标志物的结局各不相同，但骨形成标志物的异常更为一致。三份报告中有两份得出结论，骨形成参数增加酶治疗的反应，但没有描述对骨吸收markers.Conclusions的影响：在早期的假设相反，我们提出，在GD患者中，主要是骨形成减少导致骨重建的不平衡。（临床内分泌代谢杂志96：2194-2205，2011）
Context: Gaucher disease (GD) is a lysosomal storage disorder characterized by abundant presence of macrophages. Bone complications and low bone density are believed to arise from enhanced bone resorption mediated through macrophage-derived factors.Objective: The objective of the study was to investigate the relationship between bone turnover and bone complications in GD.Design: This was a retrospective cohort study and review of the literature.Patients: Forty adult type I GD patients were included in the study.Outcome Measures: Levels of the bone-resorption marker, type 1 collagen C-terminal telopeptide, and two bone-formation markers, N-terminal propeptide of type 1 procollagen and osteocalcin, were investigated in relation to clinical bone disease, measures of overall disease severity, and imaging data representing bone marrow infiltration.Results: Osteocalcin was decreased in 50% of our patients (median 0.35 nmol/liter, normal 0.4-4.0), indicating a decrease of bone formation. Type 1 collagen C-terminal telopeptide and N-terminal propeptide of type 1 procollagen were within the normal range for most patients. Osteocalcin concentration was negatively correlated to measures of overall disease severity and positively correlated with imaging data (correlation coefficient 0.423; P = 0.025), suggesting a relation with disease severity. A review of the literature revealed variable outcomes on bone resorption markers but more consistent abnormalities in bone formation markers. Two of three reports conclude that bone-formation parameters increase in response to enzyme therapy, but none describes an effect on bone-resorption markers.Conclusions: In contrast to earlier hypotheses, we propose that in GD patients, primarily a decrease in bone formation causes an imbalance in bone remodeling. (J Clin Endocrinol Metab 96: 2194-2205, 2011)