Rapid and robust response of biochemical markers of bone formation to teriparatide therapy
Rapid and robust response of biochemical markers of bone formation to teriparatide therapy
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DOI：
10.1016/j.bone.2009.07.091
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发表时间：
2009-12-01
期刊：
影响因子：
4.1
通讯作者：
John, Markus R.
中科院分区：
文献类型：
--
作者：
Glover, Sarah J.;Eastell, Richard;John, Markus R.
Teriparatide是一种甲状旁腺激素类似物，是治疗绝经后骨质疏松症的有效合成代谢药物。本研究的目的是：(1)描述用药28天期间骨转换标志物的变化；(2)确定大多数受试者对特瑞帕替德表现出生化反应的最早时间点；(3)确定骨反应阳性的潜在生物标志物；(4)描述停药4周后骨转换标志物的变化。我们招募了15名绝经后妇女，年龄55-69(平均62岁)。两组均皮下注射特瑞帕坦20 mg，疗程28天。分别于给药前3次，给药前3次，给药后第3、7、10、14、19、24、28天和第56天(即给药后56天，即给药前3次，给药前3次，给药前3次，给药后第3、7、10、14、19、24、28天和第56天，即给药前3次、给药前3次、给药后第3、7、10、14、19、24、28天和第56天，即给药前3次，给药前3次、给药后第3、7、10、14、19、24、28天和第56天，即给药前3次，给药后第3、7、10、14、19、24、28天和第56天，即给药前3次，给药前3次，给药前3次，给药后第3、7、10、14、19、24、28天)和第56天(即给药后56天，即给药前3次，给药前3次，给药后第3、7、10、14、19、24、28天)和第56天(即给药后56天，即给药前3次，给药前3次，给药后第3、7、10、14、19、24、28天)和给药后56天(即给药前停药后28天)。在停药的前2天，血浆PINP水平迅速升高，上升了8.2%(90%可信区间为6.9%，9.5%)，并持续上升至治疗结束时的110.8%。PICP和OC表现出相似的模式，但不太明显。在第28天，所有三个标记都增加了至少75%。在同一时期，骨吸收标记物出现了短暂的小幅下降。停止治疗后，到第56天，骨形成标志物的浓度下降到基线的20%以内。总而言之，骨形成标记物PINP、PICP和OC在特瑞帕特治疗的第一周表现出迅速而强劲的增长，这一点在治疗的第一周是显著的。PINP是反应最灵敏的标记。这些发现对监测服用特立帕替特的患者具有重要意义，也可能为设计治疗骨质疏松症的新的合成代谢药提供参考。(C)2009 Elsevier Inc.保留所有权利。
Teriparatide, a parathyroid hormone analogue, is a potent anabolic treatment for postmenopausal osteoporosis. Studies have shown that teriparatide induces large increases in biochemical markers of bone formation after 1 month of therapy followed by a delayed increase in bone resorption markers.The aims of this study were to (1) describe changes in bone turnover markers during 28 days of treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide.We recruited 15 osteopenic postmenopausal women, ages 55-69 (mean 62) years. All received 20 mu g teriparatide subcutaneously for 28 days. Serum levels of the bone formation markers type 1 collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), and the bone resorption markers crosslinked C-telopeptide of type I collagen (S beta-CTX), crosslinked N-telopeptide of type I collagen (S-NTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were measured on II occasions: three times before dosing (baseline) and on days 3, 7, 10, 14, 19, 24 and 28 and at day 56 (i.e., 28 days after stopping teriparatide).During the first 2 days of teriparatide treatment, PINP levels increased rapidly, by 8.2% (90% confidence interval (CI) 6.9%, 9.5%) and continued to increase until the end of treatment to 110.8%. PICP and OC showed a similar, but less pronounced, pattern. All three markers increased by at least 75% at day 28. A small, transient decrease in bone resorption markers occurred over the same period. Following cessation of treatment, concentrations of bone formation markers decreased to within 20% of baseline values by day 56. In conclusion, the bone formation markers PINP, PICP and OC show a rapid and robust increase in response to teriparatide, which is noticeable during the first week of therapy. PINP is the most responsive marker. These findings have important implications for monitoring patients treated with teriparatide and may also inform the design of studies of new anabolic agents for osteoporosis. (C) 2009 Elsevier Inc. All rights reserved.