Chronopharmacological study on the diurnal rhythms in bone metabolism.

1)测定大鼠骨内外钙转移的昼夜节律时间结构。钙在骨骼和生长门牙中的沉积高峰出现在2400h，在1200h时达到最低点，而钙在1200-1600h时从骨骼中释放量最大，在发育后期最低。研究表明，一种热敏体液因子(s)调节大鼠和人类骨吸收的昼夜节律。2)研究骨吸收阻滞剂对大鼠给药时间的影响。研究表明，大鼠对槲皮素、水杨酸钠和双膦酸盐的敏感性存在昼夜节律，这些物质已知具有低钙或抗溶骨作用。研究还表明，这些药物的低钙或抗溶骨作用的大小取决于骨吸收的昼夜节律阶段。上述结果表明，如果在设计骨吸收阻滞剂治疗方案时考虑到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.