Schlemmer A, Ravn P, Hassager C, Christiansen C
Center for Clinical & Basic Research, Ballerup Byvej, Ballerup, Denmark.
Bone. 1997 Jan;20(1):63-7. doi: 10.1016/s8756-3282(96)00307-9.
The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover study, with three 24 h studies of blood samples drawn every third hour and urine collected in 3 h aliquots was undertaken. Subjects consisted of nine healthy postmenopausal women, aged 58 +/- 7 years. Urinary CrossLaps (a measure of bone resorption) was measured by ELISA and corrected for creatinine (Cr). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during the second study. After a washing-out period of 2 weeks the participants were given 200 IE of sCT at the reverse time of the day 5 days prior to and during the third study. At all timepoints, urinary CrossLaps/Cr exhibited a significant (p < 0.001) circadian rhythm with its zenith in early morning and nadir in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The 24 h mean urinary CrossLaps/Cr and sOC remained unchanged. Both morning and evening sCT significantly decreased the urinary excretion of CrossLaps/Cr 3-6 h after administration, with a rebound effect approximately 12 h later. However, the present study does not indicate that neither evening nor twice-daily administration is superior to morning administration.
本研究的目的是探讨在早晨（8:00）或晚上（21:00）给予鼻内注射鲑鱼降钙素（sCT，200 IE）对已知的骨转换生化标志物昼夜变化的影响。进行了一项开放、安慰剂对照、随机、交叉研究，包括三项24小时研究，每三小时采集一次血样，并将尿液收集为3小时的等分试样。受试者包括9名健康的绝经后妇女，年龄为58±7岁。通过酶联免疫吸附测定（ELISA）测量尿I型胶原交联N-末端肽（CrossLaps，一种骨吸收指标），并对肌酐（Cr）进行校正。通过放射免疫测定（RIA）测量血清骨钙素（sOC）。第一项24小时研究在无干预的情况下进行。在这项对照研究之前，参与者被随机分为早晨（8:00）或晚上（21:00）给予sCT（200 IE）。在第二项研究之前和期间，在4 - 5天内给予sCT。经过2周的洗脱期后，在第三项研究之前和期间，在一天的相反时间给予参与者200 IE 的sCT。在所有时间点，尿CrossLaps/Cr均呈现显著（p < 0.001）的昼夜节律，清晨达到峰值，傍晚达到谷值。早晨和晚上给予sCT均在给药后约3 - 6小时显著降低尿CrossLaps/Cr的排泄，随后出现反弹效应。sOC未呈现显著的昼夜变化，且不受降钙素影响。24小时平均尿CrossLaps/Cr和sOC保持不变。早晨和晚上给予sCT均在给药后3 - 6小时显著降低尿CrossLaps/Cr的排泄，约12小时后出现反弹效应。然而，本研究并未表明晚上给药或每日两次给药优于早晨给药。
