Shiraki Masataka, Kuroda Tatsuhiko, Tanaka Shiro, Saito Mitsuru, Fukunaga Masao, Nakamura Toshitaka
Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano 399-8101, Japan.
J Bone Miner Metab. 2008;26(1):93-100. doi: 10.1007/s00774-007-0784-6. Epub 2008 Jan 10.
Advanced glycation end products (AGE) in collagen have been reported to decrease the mechanical property of bone. However, there are no available data on the relation between fracture risk and levels of glycoxidative (nonenzymatic) cross-links of collagen in clinical samples. A total of 432 Japanese elderly women who were not receiving any drug treatment for osteoporosis were selected and followed for 5.2 +/- 3.3 (mean +/- SD) years for this observational study. Vertebral fractures and bone mineral density were assessed at baseline and then at 1- to 2-year intervals or at indication of any symptom. Two types of collagen metabolites were measured at baseline: urinary N-terminal telopeptide of type I collagen (NTX), a marker of pyridinium cross-link, and urinary pentosidine, a nonenzymatic collagen cross-link produced by AGEs. A total of 97 incident vertebral fractures on 72 subjects were observed. Simple regression analysis using Cox's hazards model showed that log-transformed urinary NTX and pentosidine are significant risk factors for time-dependent incidence of vertebral fractures, in addition to the traditional risk factors (age, lumbar bone mineral density, and number of prevalent vertebral fractures). However, urinary excretion of pentosidine (hazard ratio, 1.33; 95% CI, 1.01-1.76, P = 0.04) was a significant predictor of incident vertebral fracture after adjustment for other traditional risk factors. The present data suggest that AGE-related collagen cross-link is a novel risk for vertebral fracture.
据报道，胶原蛋白中的晚期糖基化终末产物（AGE）会降低骨骼的力学性能。然而，关于临床样本中骨折风险与胶原蛋白糖氧化（非酶促）交联水平之间的关系，目前尚无可用数据。本观察性研究选取了432名未接受任何骨质疏松药物治疗的日本老年女性，随访5.2±3.3（均值±标准差）年。在基线时评估椎体骨折和骨密度，然后每隔1至2年或出现任何症状时进行评估。在基线时测量两种胶原蛋白代谢产物：I型胶原蛋白的尿N端肽（NTX），一种吡啶交联的标志物；以及尿戊糖苷，一种由AGEs产生的非酶促胶原蛋白交联物。共观察到72名受试者发生97例椎体骨折。使用Cox风险模型进行的简单回归分析表明，除了传统风险因素（年龄、腰椎骨密度和既往椎体骨折数量）外，对数转换后的尿NTX和戊糖苷是椎体骨折时间依赖性发生率的显著风险因素。然而，在调整其他传统风险因素后，尿戊糖苷排泄量（风险比，1.33；95%可信区间，1.01 - 1.76，P = 0.04）是椎体骨折发生的显著预测因素。目前的数据表明，与AGE相关的胶原蛋白交联是椎体骨折的一个新风险因素。
