Milovanovic Petar, Hrncic Dragan, Radotic Ksenija, Stankovic Mira, Mutavdzic Dragosav, Djonic Danijela, Rasic-Markovic Aleksandra, Djuric Dragan, Stanojlovic Olivera, Djuric Marija
Laboratory for Anthropology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Laboratory for Neurophysiology, Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Life Sci. 2017 Dec 15;191:9-16. doi: 10.1016/j.lfs.2017.10.008. Epub 2017 Oct 5.
In general, hyperhomocysteinemia is increasingly appreciated as a risk factor for various diseases, including osteoporosis. However, its effects in non-adults remain largely unknown. Our aim was to determine whether dietary-caused increased homocysteine levels have deleterious effects on bone structure during growth.
We developed a model of moderate hyperhomocysteinemia caused by short-term methionine nutritional overload in growing rats. 30-days-old male Wistar albino rats were randomly assigned to either experimental group subject to a 30-days hypermethionine diet or control group. High-resolution 3D assessment of bone geometry and microarchitecture, as well as fluorescence spectroscopic analysis of bone matrix were performed.
Short-term moderate hyperhomocysteinemia (~30μmol/L) achieved in the study notably affected bone and cartilage characteristics. Parameters of the cortical bone geometry in the experimental group indicated peculiar reorganization of the bone cross-section. Trabecular bone microarchitecture was especially sensitive to hyperhomocysteinemia showing clearly negative bone balance in the experimental group (almost 30% reduced bone volume, mainly due to ~25% decrease in trabecular number as well as markedly reduced trabecular connections). Fluorescent spectroscopy of bone matrix revealed multiple alterations to collagen spectra due to homocysteine accumulation in bone, indicative of broken collagenous cross-links.
Given that appropriate accrual of bone mass during growth has important effects on the risk of osteoporosis in adulthood, understanding the skeletal effects of dietary-induced hyperhomocysteinemia in non-adults is essential for interpreting its importance as a modifiable risk factor for osteoporosis and improving programs to preserve/re-establish bone health.
一般而言，高同型半胱氨酸血症作为包括骨质疏松症在内的各种疾病的风险因素，越来越受到重视。然而，其在非成年人中的影响在很大程度上仍不清楚。我们的目的是确定饮食引起的同型半胱氨酸水平升高是否会对生长期间的骨骼结构产生有害影响。
我们建立了一个由生长中大鼠短期蛋氨酸营养过载引起的中度高同型半胱氨酸血症模型。将30日龄雄性Wistar白化大鼠随机分为接受30天高蛋氨酸饮食的实验组或对照组。对骨几何结构和微结构进行高分辨率三维评估，以及对骨基质进行荧光光谱分析。
本研究中实现的短期中度高同型半胱氨酸血症（约30μmol/L）显著影响骨骼和软骨特征。实验组皮质骨几何结构参数表明骨横截面有特殊的重组。小梁骨微结构对高同型半胱氨酸血症特别敏感，实验组显示明显的负骨平衡（骨体积减少近30%，主要是由于小梁数量减少约25%以及小梁连接明显减少）。骨基质的荧光光谱显示由于同型半胱氨酸在骨中的积累，胶原光谱发生了多种改变，表明胶原交联断裂。
鉴于生长期间适当的骨量积累对成年期骨质疏松症风险有重要影响，了解饮食诱导的高同型半胱氨酸血症在非成年人中的骨骼影响对于解释其作为骨质疏松症可改变风险因素的重要性以及改善维持/重建骨骼健康的方案至关重要。
