Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus.
Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone From Fractured Patients With Type 1 Diabetes Mellitus.
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DOI：
10.1002/jbmr.2607
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发表时间：
2016-01
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影响因子：
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通讯作者：
Boivin G
中科院分区：
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作者：
Farlay D;Armas LA;Gineyts E;Akhter MP;Recker RR;Boivin G
低能量骨折是1型糖尿病（T1DM）患者常见的并发症。骨固有成分的改变可能是糖尿病受试者中观察到的脆性的潜在原因。在T1DM患者的许多结缔组织中发现了晚期糖基化终产物（AGEs）。然而，AGEs是否以高水平存在于糖尿病受试者的骨基质中尚不清楚。此外，骨基质中AGEs的升高是否会损害矿化尚未在人类中得到解决。本研究的目的是1）确定骨折和非骨折T1DM的骨基质是否比健康患者（CTL）的骨含有更多的AGEs，2）比较骨折和非骨折T1DM与CTL之间的骨矿化程度和硬度。我们分析了年龄和性别匹配的5例骨折（1型糖尿病）T1DM患者、5例非骨折T1DM患者和5例健康受试者的髂嵴骨活检。采用高效液相色谱法分别测定松质骨和皮质骨基质中AGEs的含量。骨矿化度（DMB）通过数字化显微放射照相术进行评估，力学性能通过显微和纳米硬度测试进行评估。骨折T1DM的松质骨中Pentosidine水平显著高于CTL（p=0.04），矿化程度高于非骨折T1DM（p=0.04）和CTL（p=0.04）。非骨折性T1DM和CTL之间的松质骨中戊糖苷没有显著差异。非骨折性T1DM的皮质骨与CTL无显著差异。HbA1c与Pentosidine呈正相关（r′= 0.79，p <0.003），与DMB呈正相关（r′= 0.64，p <0.02）。两种改良均可能导致T1DM患者的骨弹性降低（弹性模量降低），并倾向于低能量骨折。
Low-energy fractures are frequent complications in Type 1 Diabetes Mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced Glycation End-products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and non-fracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and non-fracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing (Type 1 Diabetes Mellitus) T1DM patients, 5 non-fracturing T1DM patients and 5 healthy subjects, all age- and sex-matched. AGEs (Pentosidine) in bone matrix was measured by high performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro- and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of Pentosidine than CTL (p=0.04) and was more mineralized than non-fracturing T1DM (p=0.04) and CTL (p=0.04). Trabecular bone was not significantly different in pentosidine between non-fracturing T1DM and CTL. Cortical bone from non-fracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and Pentosidine (r′=0.79, p<0.003), and between HbA1c and DMB (r′=0.64, p<0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity), and a tendency toward low-energy fractures in T1DM patients.