甲状旁腺激素对2型糖尿病大鼠皮质骨孔隙率、非酶糖基化及骨组织力学的影响

Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.

作者信息

Campbell G M, Tiwari S, Hofbauer C, Picke A-K, Rauner M, Huber G, Peña J A, Damm T, Barkmann R, Morlock M M, Hofbauer L C, Glüer C-C

机构信息

Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany; Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.

Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.

出版信息

Bone. 2016 Jan;82:116-21. doi: 10.1016/j.bone.2015.04.049. Epub 2015 May 5.

DOI:10.1016/j.bone.2015.04.049

PMID:25952971

Abstract

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75μg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs. untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=-0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert: R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes".

摘要

2型糖尿病会增加骨骼脆性；然而，其作用机制以及成骨药物的疗效尚不清楚。我们研究了糖尿病和甲状旁腺激素（PTH）治疗对Zucker糖尿病脂肪（ZDF）大鼠皮质骨孔隙率（Ct.Po）、非酶糖基化（NEG）和骨力学的影响。11周龄的ZDF糖尿病（DB）和非糖尿病（ND）大鼠每周5天接受75μg/kg PTH（1-84）或赋形剂治疗，持续12周。切除右侧股骨和L4椎体，进行显微CT扫描，并分别进行三点弯曲和单轴压缩测试。使用荧光法测定样本的NEG。糖尿病增加了Ct.Po（椎体（vert）：+40.6%，股骨（fem）：+15.5%，与ND组相比，p<0.05），但对NEG没有影响。PTH治疗仅降低了ND动物的椎体NEG（与未治疗组相比降低了-73%，p<0.05），而与ND组相比增加了DB组的股骨NEG（+63%，p<0.05）。PTH治疗对Ct.Po没有影响。糖尿病对骨组织力学产生负面影响，与ND组相比，DB组椎体最大应变（-22%）和韧性（-42%）降低（p<0.05）。PTH改善了ND动物椎体的最大应变（+21%，p<0.05），但对DB组没有影响。PTH增加了ND组的股骨最大应变（+21%）和韧性（+28%），并降低了DB动物的股骨最大应力（-13%）和韧性（-27%）（治疗组与未治疗组相比，p<0.05）。Ct.Po与最大应力（股骨：R=-0.35，p<0.05，椎体：R=-0.57，p<0.01）、最大应变（股骨：R=-0.35，p<0.05，椎体：R=-0.43，p<0.05）和韧性（股骨：R=-0.34，p<0.05，椎体：R=-0.55，p<0.01）呈负相关，NEG与股骨韧性（R=-0.34，p<0.05）和椎体最大应变（R=-0.49，p<0.05）呈负相关。糖尿病增加了皮质骨孔隙率并降低了骨力学性能，PTH治疗并未改善这些情况。单独的PTH治疗可能会通过形成具有高晚期糖基化终产物交联的新骨而使糖尿病骨力学性能恶化。最佳治疗方案必须同时解决骨量增加和血糖控制问题，以便成功降低糖尿病性骨脆性。本文是名为“骨与糖尿病”的特刊的一部分。