High W B, Capen C C, Black H E
Am J Pathol. 1981 Jul;104(1):41-9.
The effects of intermittent low doses (1.25 mug daily, administered intravenously for 6 days and withdrawn for 14 days for 3 complete cycles) of 1,25-dihydroxycholecalciferol (1,25-OHD(3)) on cortical bone were determined and compared in ribs with steady state and regionally accelerated remodeling in adult intact female dogs. The bone changes were analyzed by dynamic bone histomorphometric methods, using tetracycline and DCAF (2,4 BIS) N, N' di (carboxymethyl) (amino methyl fluorescein) in vivo double labeling of bones before treatment and after 60 days of intermittent 1,25-(OH)(2)D(3) administration. Serum calcium and phosphorus levels increased during 1,25-(OH)(2)D(3) administration. Urinary hydroxyproline excretion increased during the first interval of 1,25-(OH)(2)D(3) administration but was not changed significantly during the last two intervals. In normal cortical bone (11th rib) following the administration of 1,25-(OH)(2)D(3) there was a marked decrease in the activation frequency, bone formation rate, osteoid seam thickness, seam circumference, and mean appositional rate. Although recruitment of new remodeling sites was decreased after 1,25-(OH)(2)D(3), previously existing remodeling units continued to completion. These effects resulted in a preponderance of mature osteons in normal cortical bone. The morphometric changes in cortical bone (9th rib) exposed to both 1,25-(OH)(2)D(3) and periosteal elevation were characterized by a marked increase in both the activation frequency and bone formation rate and associated with a decrease in the osteon formation time. Other morphometric parameters that were increased included radial closure rate, numbers of osteoid seams and resorption cavities, ratio of bone resorbing to forming sites, percentage labeled and circumference of osteoid seams, and total and cortical bone areas. The combined effect of periosteal elevation and 1,25-(OH)(2)D(3) were markedly different from those observed with 1,25-(OH)(2)D(3) alone. These findings suggest that the rapid bone turnover induced by tissue injury will mask or alter the effects of hormones on bone remodeling when studied over a relatively short period of time.
测定并比较了间歇性低剂量（每日1.25微克，静脉注射6天，停药14天，共3个完整周期）的1,25 - 二羟胆钙化醇（1,25-OHD(3)）对成年未孕雌性犬肋骨皮质骨的影响，这些肋骨处于稳态和局部加速重塑状态。在治疗前以及间歇性给予1,25-(OH)(2)D(3) 60天后，使用四环素和双醋酸荧光素（DCAF，2,4 - 双[（羧甲基）（氨基甲基）]荧光素）对骨骼进行体内双重标记，通过动态骨组织形态计量学方法分析骨变化。在给予1,25-(OH)(2)D(3)期间，血清钙和磷水平升高。在给予1,25-(OH)(2)D(3)的第一个时间段内，尿羟脯氨酸排泄增加，但在最后两个时间段内无显著变化。给予1,25-(OH)(2)D(3)后，正常皮质骨（第11肋）的激活频率、骨形成率、类骨质缝厚度、缝周长和平均沉积率显著降低。尽管给予1,25-(OH)(2)D(3)后新重塑位点的募集减少，但先前存在的重塑单元仍继续完成。这些效应导致正常皮质骨中成熟骨单位占优势。暴露于1,25-(OH)(2)D(3)和骨膜抬高的皮质骨（第9肋）的形态计量学变化特征为激活频率和骨形成率均显著增加，并伴有骨单位形成时间缩短。其他增加的形态计量学参数包括径向闭合率、类骨质缝和吸收腔数量、骨吸收与形成位点的比例、类骨质缝的标记百分比和周长以及总骨面积和皮质骨面积。骨膜抬高和1,25-(OH)(2)D(3)的联合效应与单独使用1,25-(OH)(2)D(3)时观察到的效应明显不同。这些发现表明，在相对较短的时间内进行研究时，组织损伤诱导的快速骨转换将掩盖或改变激素对骨重塑的影响。
