The effect of calcium supplementation on the circadian rhythm of bone resorption

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.