Regional Bone Center, Helen Hayes Hospital, West Haverstraw, New York 10993, USA.
J Clin Endocrinol Metab. 2012 Aug;97(8):2799-808. doi: 10.1210/jc.2012-1262. Epub 2012 Jun 14.
Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling.
We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL).
This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study.
The study was conducted at 12 U.S. and Canadian centers.
Healthy postmenopausal women with osteoporosis participated in the study.
Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35).
The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured.
Among 58 subjects with evaluable biopsies (TPTD = 28; ZOL = 30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P < 0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P < 0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points.
TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.
最近对骨活性药物作用机制（MOA）的研究重新燃起了人们对如何呈现和解释骨重建的动态组织形态计量学参数的兴趣。
我们比较了一种已确立的合成代谢药物特立帕肽（TPTD）和一种典型的抗吸收药物唑来膦酸（ZOL）的作用。
这是一项为期 12 个月、随机、双盲、活性对照、交叉活检研究。
该研究在美国和加拿大的 12 个中心进行。
患有骨质疏松症的健康绝经后妇女参加了这项研究。
受试者接受每日一次 sc 注射 TPTD 20 μg（n = 34）或基线时 iv 输注 ZOL 5 mg（n = 35）。
主要终点是第 6 个月的矿化表面/骨表面（MS/BS），这是骨形成的动态测量。还评估了一组标准的动态和静态组织形态计量学指标。当遇到没有标签的标本时，使用了几种方法来计算矿化率（MAR）。还测量了血清骨转换标志物。
在 58 名具有可评估活检标本的受试者中（TPTD = 28；ZOL = 30），TPTD 组的 MS/BS 显著更高（中位数：5.60%对 0.16%，P < 0.001）。TPTD 组的其他骨形成指标，包括 MAR，也较高（P < 0.05）。TPTD 分别在第 1、3、6 和 12 个月显著增加了前胶原 I 氨基端前肽（PINP），并在第 3 至 12 个月显著降低了 I 型胶原羧基端交联端肽（CTX）。ZOL 分别在所有时间点均显著低于基线降低了 PINP 和 CTX。
基于对骨形成的组织形态计量学数据和血清标志物的分析，TPTD 和 ZOL 具有根本不同的作用机制，对骨形成的作用相反。一个重要的机制差异是 TPTD 组的 MS/BS 显著更高。总的来说，这些结果定义了这两种药物治疗后与抗吸收活性相比的合成代谢活性的动态组织形态计量学特征。
