Metabolic Bone Disease Center, State University of New York Upstate Medical University, New York, NY, USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
J Bone Miner Res. 2022 Feb;37(2):265-272. doi: 10.1002/jbmr.4466. Epub 2021 Nov 24.
Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24-1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94-1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR).
在骨中，晚期糖基化终产物（AGE）的积累会改变胶原蛋白的结构和功能。荧光 AGE 与骨折有关，但关于非荧光 AGE 的了解较少。我们检查了羧甲基赖氨酸（CML）与 2 型糖尿病（T2D）状态下的临床新发骨折和常见椎骨骨折之间的关系，该研究纳入了老年人健康、衰老和身体成分队列。评估了临床新发骨折和基线椎骨骨折。使用 Cox 回归分析血清 CML 与临床骨折发生率之间的关系，使用逻辑回归分析椎骨骨折的患病率。在基线时，T2D（n=712）和非糖尿病（n=2332）患者的平均年龄（±标准差）分别为 73.7±2.8 岁和 73.6±2.9 岁。T2D 患者的基线 CML 水平高于非糖尿病患者（893±332 与 771±270ng/ml，p<0.0001）。在多变量模型中，更高的 CML 与 T2D 患者发生临床新发骨折的风险增加相关（风险比[HR]1.49；95%置信区间[CI]每增加 1-SD 对数 CML，增加 1.24-1.79），而非糖尿病患者则无相关性（HR 1.03；95%CI，0.94-1.13；p 交互作用=0.001）。这种相关性独立于骨密度（BMD）、糖化血红蛋白（血红蛋白 A1c）、体重、体重减轻、吸烟、胱抑素-C 和药物使用。在两组患者中，CML 与常见椎骨骨折的几率均无显著相关性。总之，在 T2D 中，更高的 CML 水平与临床新发骨折的风险增加相关，且与 BMD 无关。这些结果表明 CML 参与了糖尿病患者骨脆弱的发病机制。2021 年美国骨骼与矿物质研究协会（ASBMR）。
