Department of Kinesiology, Temple University, Philadelphia, PA 19122, USA.
Bone. 2011 Oct;49(4):810-8. doi: 10.1016/j.bone.2011.07.019. Epub 2011 Jul 23.
Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n=10), GnRH-a group (n=10), and Energy Restriction (ER, n=12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals' intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression.
青春期的下丘脑性闭经和能量限制会影响峰值骨量的积累。有一种假说认为，能量限制会改变下丘脑的功能，导致雌二醇水平降低，从而导致骨质流失。然而，关于能量限制和骨强度，既有阳性结果，也有阴性结果。因此，本研究旨在探讨青春期启动时的能量限制和下丘脑抑制对两种模型中骨机械强度和骨髓源性细胞成骨能力的影响：接受促性腺激素释放激素拮抗剂（GnRH-a）或 30%能量限制的雌性大鼠。在 23 天时，将雌性 Sprague Dawley 大鼠分为三组：对照组（C，n=10）、GnRH-a 组（n=10）和能量限制（ER，n=12）组。GnRH-a 动物每天接受注射 27 天。ER 组的动物接受了对照组动物摄入量的 70%。处死（50 日龄）后，测量体重、子宫和肌肉重量。培养骨髓源性基质细胞并检测其增殖和分化为成骨细胞的能力。测量指标包括骨强度、骨组织形态计量学和结构、血清 IGF-1 和骨钙素。GnRH-a 抑制了子宫重量，降低了成骨细胞增殖、骨强度、小梁骨体积和小梁骨结构，与对照组相比。发现血清 IGF-1 和骨钙素水平升高，体重增加。与 GnRH-a 组相比，ER 模型中成骨细胞增殖增加，与体重相比骨强度相对增加，与对照组相比腰椎小梁骨体积增加。ER 动物较小，但骨骼强度足以支撑其体重。相比之下，通过下丘脑抑制抑制雌二醇会导致骨强度不足和小梁骨体积丢失。总之，我们的结果支持这样一种假说，即在营养压力期间，增加的椎体骨体积可能是一种储存矿物质的适应机制，这与下丘脑抑制导致的雌二醇降低不同。
