Blumsohn A, Herrington K, Hannon R A, Shao P, Eyre D R, Eastell R
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, England.
J Clin Endocrinol Metab. 1994 Sep;79(3):730-5. doi: 10.1210/jcem.79.3.8077353.
Bone resorption shows a circadian rhythm in human subjects, but the physiological mechanisms underlying this rhythm are unknown. We compared the circadian rhythm of bone collagen degradation in 18 premenopausal women before and after oral calcium supplementation (1000 mg calcium for 14 days). Subjects were randomized to receive calcium at either 0800 h or 2300 h. Continuous 48-h urine collections and 1 day of 4-h urine collections were obtained before and after the 14-day supplementation period. We measured urinary deoxypyridinoline (Dpd) and the cross-linked N-telopeptide of type I collagen (NTx) as biochemical markers of bone resorption. There was a significant effect of time of day on excretion of Dpd and NTx (analysis of variance, P < 0.001) with peak excretion between 0300-0700 h and a nadir between 1500-1900 h. The mean amplitude (peak to trough) was similar for Dpd and NTx (70.3% and 63.3%, respectively). Evening calcium supplementation resulted in marked suppression of the nocturnal increase in Dpd and NTx and reversed the usual nocturnal increase in the level of parathyroid hormone. In contrast, morning calcium supplementation had no significant effect on the circadian rhythm of Dpd or NTx. Evening calcium supplementation suppressed overall daily excretion of Dpd by 20.1% (P = 0.03) and NTx by 18.1% (P = 0.03). Morning calcium supplementation had no significant effect on overall daily excretion of either Dpd or NTx. We conclude that evening calcium supplementation suppresses the circadian rhythm of bone resorption. The daily rhythm of PTH secretion or calcium intake is likely to be an important determinant of this rhythm. Experimental protocols designed to investigate the effect of calcium supplementation on bone mineral density should take the timing of supplementation into account.
在人类受试者中，骨吸收呈现昼夜节律，但这种节律背后的生理机制尚不清楚。我们比较了18名绝经前女性在口服补钙（1000毫克钙，持续14天）前后骨胶原降解的昼夜节律。受试者被随机分为在08:00或23:00服用钙。在为期14天的补充期前后，分别进行了连续48小时的尿液收集和1天的4小时尿液收集。我们测量了尿脱氧吡啶啉（Dpd）和I型胶原交联N-端肽（NTx）作为骨吸收的生化标志物。一天中的时间对Dpd和NTx的排泄有显著影响（方差分析，P<0.001），排泄高峰在03:00 - 07:00之间，最低点在15:00 - 19:00之间。Dpd和NTx的平均幅度（峰值到谷值）相似（分别为70.3%和63.3%）。晚间补钙导致Dpd和NTx夜间升高明显受到抑制，并逆转了甲状旁腺激素水平通常的夜间升高。相比之下，早晨补钙对Dpd或NTx的昼夜节律没有显著影响。晚间补钙使Dpd的总体日排泄量降低了20.1%（P = 0.03），NTx降低了18.1%（P = 0.03）。早晨补钙对Dpd或NTx的总体日排泄量没有显著影响。我们得出结论，晚间补钙可抑制骨吸收的昼夜节律。甲状旁腺激素分泌或钙摄入的每日节律可能是这种节律的重要决定因素。旨在研究补钙对骨密度影响的实验方案应考虑补钙的时间。
