Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Bone. 2010 May;46(5):1344-8. doi: 10.1016/j.bone.2009.11.027. Epub 2009 Nov 27.
Severe hyperhomocysteinemia, as seen in classic homocystinuria, is associated with several skeletal malformations and osteopenia. Moreover, hyperhomocysteinemia during pregnancy has been associated with multiple developmental defects in the fetus. This study was undertaken to determine whether offspring of hyperhomocysteinemic mothers have demonstrable changes in bone volume and the epiphyseal growth plate. Ten adult female Sprague-Dawley rats were randomly assigned to the control or experimental group. The experimental group received 100 mg/kg/day of homocysteine in their drinking water for 3 weeks before mating and for the total duration of pregnancy. In each group, three pups per mother were randomly selected. The histomorphometric properties of tibial, radial and vertebral growth plates of newborn rats and the volume fraction of bone were compared between groups. The plasma homocysteine concentration at the end of study was significantly higher in dams in the experimental group (16.42+/-1.5 vs. 4.7+/-1.7 mumol/L, P<0.05). In offspring born to dams given the homocysteine supplement, the volume fraction of bone in the tibia (30.7+/-1.5% vs. 36.8+/-1.9%, P<0.05), radius (29.6+/-1.1% vs. 37.4+/-2%, P<0.05) and vertebra (34.4+/-1.8% vs. 41+/-1.9%, P<0.05) were significantly decreased whereas vertical heights of proliferative (423+/-25.1 vs. 301.8+/-28.1 microm for radius and 131.9+/-5.9 vs. 107.8+/-3.5 microm for vertebra) and hypertrophic zones (213.1+/-12 vs. 163.3+/-7.5 microm for tibia, 153.2+/-7.7 vs. 121.1+/-7.9 microm for radius and 112+/-9.9 vs. 88.4+/-10.1 microm for the vertebra) were increased (P<0.05). The results showed that the administration of homocysteine caused osteopenia in newborn rats. In addition, these data suggest that hyperhomocysteinemia may induce disruption of normal development of epiphyseal cartilage in the rat embryo.
严重的高同型半胱氨酸血症，如经典同型胱氨酸尿症所见，与多种骨骼畸形和骨质疏松症有关。此外，怀孕期间的高同型半胱氨酸血症与胎儿的多种发育缺陷有关。本研究旨在确定高同型半胱氨酸血症母亲的后代是否存在骨量和骺板生长板的明显变化。10 只成年雌性 Sprague-Dawley 大鼠被随机分配到对照组或实验组。实验组在交配前和整个孕期每天接受 100mg/kg 的同型半胱氨酸饮用水。在每组中，从每个母亲中随机选择 3 只幼崽。比较新生大鼠胫骨、桡骨和椎体生长板的组织形态计量学特性和骨体积分数。研究结束时，实验组母鼠的血浆同型半胱氨酸浓度显著升高（16.42+/-1.5 与 4.7+/-1.7 umol/L，P<0.05）。在接受同型半胱氨酸补充的母鼠所生的后代中，胫骨（30.7+/-1.5%与 36.8+/-1.9%，P<0.05）、桡骨（29.6+/-1.1%与 37.4+/-2%，P<0.05）和椎体（34.4+/-1.8%与 41+/-1.9%，P<0.05）的骨体积分数显著降低，而增殖带（423+/-25.1 与 301.8+/-28.1 um 对于桡骨和 131.9+/-5.9 与 107.8+/-3.5 um 对于椎体）和肥大带（213.1+/-12 与 163.3+/-7.5 um 对于胫骨，153.2+/-7.7 与 121.1+/-7.9 um 对于桡骨和 112+/-9.9 与 88.4+/-10.1 um 对于椎体）的垂直高度增加（P<0.05）。结果表明，同型半胱氨酸的给药导致新生大鼠骨质疏松症。此外，这些数据表明，高同型半胱氨酸血症可能导致大鼠胚胎骺板软骨的正常发育中断。
