Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: A Randomized Controlled Trial
Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: A Randomized Controlled Trial
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DOI：
10.1210/jc.2012-1262
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发表时间：
2012-08-01
影响因子：
5.8
通讯作者：
Taylor, Kathleen A.
中科院分区：
文献类型：
--
作者：
Dempster, David W.;Zhou, Hua;Taylor, Kathleen A.
背景：最近对骨活性药物作用机制（MOA）的研究重新引起了人们对如何呈现和解释骨重塑的动态组织形态学参数的兴趣。目的：我们比较了一种合成代谢药物特立帕肽（TPTD）与一种原型抗吸收药物唑来膦酸（ZOL）的作用。设计：这是一项为期12个月的随机、双盲、主动对照、横断面活检研究。环境：该研究在美国和加拿大的12个中心进行。研究对象：健康的绝经后骨质疏松妇女参与研究。干预措施：受试者在基线时静脉注射ZOL 5 mg (n = 35)，每日1次皮下注射ttptd 20 mu g （n = 34）。主要结局指标：第6个月时，主要终点是矿化表面/骨表面（MS/BS），这是骨形成的动态指标。动态和静态组织形态计量指标的标准面板也进行了评估。当遇到缺少标签的标本时，使用几种方法计算矿物堆积率（MAR）。同时测定骨转换的血清标志物。结果：在58例可评估活检的受试者中（TPTD = 28, ZOL = 30）， TPTD组MS/BS显著高于ttptd组（中位数：5.60 vs. 0.16%, P < 0.001）。其他骨形成指标，包括MAR， TPTD组均高于对照组（P < 0.05）。TPTD在第1、3、6和12个月显著增加1型胶原n端前肽（PINP），在第3至12个月显著增加1型胶原羧基端交联末端肽（CTX）。ZOL在所有时间点显著降低PINP和CTX低于基线。结论：TPTD和ZOL具有完全不同的作用机制，对骨形成的影响相反，基于组织形态学数据和骨形成和吸收的血清标志物分析。一个重要的机制差异是TPTD组的MS/BS明显较高。总的来说，这些结果确定了这两种药物治疗后合成代谢活性相对于抗吸收活性的动态组织形态学特征。[J] .中华内分泌杂志，2012,31(5):389 - 398。
Context: 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.Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL).Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study.Setting: The study was conducted at 12 U.S. and Canadian centers.Subjects: Healthy postmenopausal women with osteoporosis participated in the study.Interventions: Subjects received TPTD 20 mu g once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35).Main Outcome Measures: 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.Results: 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.Conclusions: 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. (J Clin Endocrinol Metab 97: 2799-2808, 2012)