Gertz B J, Clemens J D, Holland S D, Yuan W, Greenspan S
Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Calcif Tissue Int. 1998 Aug;63(2):102-6. doi: 10.1007/s002239900497.
Biochemical markers of bone turnover are finding increased application in the investigation and management of skeletal diseases such as osteoporosis. The present study assessed for the first time the diurnal variation of serum type I collagen cross-linked N-telopeptides (NTx), a new serum-based marker of bone resorption, and the effect of antiresorptive therapy with alendronate on this marker in elderly osteopenic women. The concentrations of serum NTx were monitored over 24 hours in a randomly selected subset of 38 women (placebo n = 13, 69 +/- 3 (SD) year; alendronate n = 25, 69 +/- 3 year), who had completed 12-15 months of a larger (n = 120) randomized, double-blind, parallel group, placebo-controlled trial with alendronate 5 mg/day. Blood was obtained every 4 hours for measurement of serum NTx using a new chemiluminescent-based immunoassay. There was a significant diurnal variation of serum NTx (p = 0.001) in both the placebo and alendronate groups. Mean peak levels occurred at approximately 0504 h with a mean nadir at approximately 1320 h in the placebo group, with no significant difference on alendronate. Serum NTx was approximately 25% lower in the alendronate group over the entire 24-hour period. Mean (SE) daytime (0800-2000) and nighttime (2200-0800) serum NTx values were 6.40 +/- 0.30 versus 8.45 +/- 0.58 nmol BCE/liter, and 7.42 +/- 0.23 versus 10.01 +/- 0.53 nmol BCE/liter for alendronate versus placebo, respectively (P < or = 0.003 for both comparisons). Combining the data of both treatment groups, serum NTx was significantly (P < 0.05) correlated with serum osteocalcin (r = 0.753) and urine NTx (r = 0.628) measurements previously obtained over the entire 24-hour period. Serum NTx has a significant diurnal variation and is responsive to antiresorptive therapy with alendronate. Alendronate reduces the amplitude but maintains the pattern of the 24-hour serum NTx profile. These data suggest that serum NTx may be a useful new marker of bone resorption.
骨转换生化标志物在骨质疏松等骨骼疾病的研究和管理中的应用越来越广泛。本研究首次评估了血清I型胶原交联N端肽（NTx）这一新型骨吸收血清标志物的昼夜变化，以及阿仑膦酸钠抗吸收治疗对老年骨质减少女性该标志物的影响。在38名女性（安慰剂组n = 13，年龄69±3（标准差）岁；阿仑膦酸钠组n = 25，年龄69±3岁）的随机子集中，对其血清NTx浓度进行了24小时监测，这些女性完成了一项更大规模（n = 120）的随机、双盲、平行组安慰剂对照试验，试验中每天服用5毫克阿仑膦酸钠，为期12 - 15个月。每4小时采集一次血液，使用基于化学发光的新型免疫测定法测量血清NTx。安慰剂组和阿仑膦酸钠组的血清NTx均存在显著的昼夜变化（p = 0.001）。安慰剂组平均峰值水平出现在约0504时，平均谷值出现在约1320时，阿仑膦酸钠组无显著差异。在整个24小时期间，阿仑膦酸钠组的血清NTx约低25%。阿仑膦酸钠组与安慰剂组白天（0800 - 2000）和夜间（2200 - 0800）血清NTx的平均（标准误）值分别为6.40±0.30与8.45±0.58 nmol BCE/升，以及7.42±0.23与10.01±0.53 nmol BCE/升（两组比较P均≤0.003）。综合两个治疗组的数据，血清NTx与之前在整个24小时期间测得的血清骨钙素（r = 0.753）和尿NTx（r = 0.628）显著相关（P < 0.05）。血清NTx有显著的昼夜变化，并且对阿仑膦酸钠抗吸收治疗有反应。阿仑膦酸钠降低了幅度，但维持了24小时血清NTx曲线的模式。这些数据表明血清NTx可能是一种有用的新型骨吸收标志物。
