High W B, Capen C C, Black H E
Am J Pathol. 1981 Dec;105(3):279-87.
The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), parathyroid hormone (PTH), and L-thyroxine (T4) on trabecular bone remodeling were evaluated by histomorphometric methods in adult female beagle dogs. Intravenous 1,25-(OH)2D3 (1.25 micrograms/day in equally divided doses) was administered intermittently for 6 days and withdrawn 14 days for three complete cycles. PTH was administered intravenously (2.5 U/kg/day) in divided doses 6 hours apart for 60 days. Thyroxine was given orally (1.0 mg/kg/day) in divided doses for a similar interval. Static and dynamic changes were evaluated using tetracycline and DCAF (2,4 BIS) N, N', Di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bone from the iliac crest taken before treatment and after 60 days. The intermittent administration of 1,25-(OH)2D3 stimulated the bone resorption rate and depressed the formation rate. 1,25-(OH)2D3 increased trabecular resorption surfaces; osteoid surface, volume, and thickness; mineralization lag time; and osteoblast number but decreased the bone volume. Multiple small daily doses of PTH resulted in an overall negative balance in trabecular bone. This was associated with an increased trabecular surface-to-volume ratio, bone resorption and formation rates, active forming surfaces, osteoid volume and surface, life span of bone forming and resorbing sites, and the number of osteoclast nuclei. Thyroxine appeared to increase bone mass by enhancing the switch-over from the resorptive to the formative phase of remodeling. Coupling between osteoid apposition and mineralization was increased by recruiting more forming sites and prolonging their life span. Thyroxine increased bone resorption and formation rates, trabecular bone volume and balance, number of osteoclast nuclei, and life span of bone forming sites. The osteoid seam thickness and mineralization lag time were decreased. The present study demonstrated that 1,25-(OH)2D3, PTH, and thyroxine at the dose and schedule used, markedly altered stimulators of remodeling in trabecular bone of adult dogs.
采用组织形态计量学方法，在成年雌性比格犬中评估了1,25 - 二羟胆钙化醇（1,25-(OH)₂D₃）、甲状旁腺激素（PTH）和L - 甲状腺素（T₄）对小梁骨重塑的影响。静脉注射1,25-(OH)₂D₃（1.25微克/天，分等份剂量），间歇性给药6天，停药14天，共三个完整周期。PTH静脉注射（2.5 U/kg/天），分剂量每6小时一次，共给药60天。甲状腺素口服（1.0 mg/kg/天），分剂量给药相似时间间隔。使用四环素和DCAF（2,4 - 双）N，N'，二（羧甲基）（氨基甲基荧光素）对治疗前和60天后取自髂嵴的骨进行体内双重标记，评估静态和动态变化。间歇性给予1,25-(OH)₂D₃刺激骨吸收速率并降低形成速率。1,25-(OH)₂D₃增加小梁吸收表面；类骨质表面、体积和厚度；矿化延迟时间；以及成骨细胞数量，但降低骨体积。每日多次小剂量PTH导致小梁骨总体呈负平衡。这与小梁表面积与体积比增加、骨吸收和成骨速率、活跃形成表面、类骨质体积和表面、骨形成和吸收部位的寿命以及破骨细胞核数量增加有关。甲状腺素似乎通过增强从骨吸收到骨形成重塑阶段的转换来增加骨量。通过招募更多形成部位并延长其寿命，类骨质沉积与矿化之间的耦合增加。甲状腺素增加骨吸收和成骨速率、小梁骨体积和平衡、破骨细胞核数量以及骨形成部位的寿命。类骨质缝厚度和矿化延迟时间降低。本研究表明，以所用的剂量和给药方案给予1,25-(OH)₂D₃、PTH和甲状腺素，可显著改变成年犬小梁骨重塑的刺激因素。
