Chronopharmacological study on the diurnal rhythms in bone metabolism.

1)测定了大鼠骨钙转运昼夜节律的时间结构。骨钙沉积和切牙生长的高峰出现在2400 h，最低点出现在1200 h，骨钙释放在1200- 1600 h达到高峰，后期最低。研究表明，热敏性体液因子调节大鼠和人类骨吸收的昼夜节律。2)使用骨吸收阻滞剂在大鼠中研究了给药时间的影响。结果表明，大鼠对依卡宁、水杨酸钠和双膦酸盐的敏感性存在昼夜节律，已知这些药物具有低钙或抗溶骨性作用。研究还表明，这些药物的低钙或抗溶骨性作用的大小取决于骨吸收的昼夜节律的阶段。上述结果表明，如果在设计骨吸收阻滞剂治疗方案时考虑骨代谢的昼夜节律性，可能会获得更可预测和有效的结果。

1) Time structure of diurnal rhythms in calcium transfer in and out of bone was determined in rats. Peak deposition of calcium into bone and growing incisor occurred at 2400h, with a nadir at 1200h, while, calcium release from bone was maximal around 1200-1600h and lowest late in the dard period. It was shown that a heat sensitive humoral factor(s) regulates diurnal rhythms in bone resorption in rats and in humans. 2) The effect of the time of drug administration was studied in rats using blockers of bone resorption. It was shown that there is a diurnal rhythm in the susceptibility of rats to elcatonin, sodium salicylate and bisphosphonates, which are known to have hypo calcemic or anti-osteolytic action. It was also shown that the magnitude of hypocalcemic or anti-osteolytic effects of these drugs depend on the phase of diurnal rhythms in bone resorption. The above results suggest that more predictable and efficacious results might be attained if the diurnal rhythmicities in bone metabolism were taken into consideration in designing treatment regimens with blockers of bone resorption.