Circadian rhythms in bone resorption and the effects of blockers of bone resorption

在本研究中，讨论了钙代谢的昼夜波动的意义，特别是骨吸收活性的大鼠，与骨吸收阻滞剂的管理。生理状态下，大鼠血清钙、钙向骨转移和钙从骨中释放均具有昼夜节律。骨吸收阻滞剂的作用强度也随给药时间的不同而逐日变化，这表明靶部位（骨吸收过程）对药物的敏感性也逐日变化。因此，如果在骨吸收活跃期间使用骨吸收阻滞剂，效果会很大，如果在骨吸收不活跃期间使用，效果就会减弱。在钙代谢领域，给药时间或实验方法迄今为止更多地基于传统的体内平衡假说。体内平衡假说认为，化学药剂的药理学和毒理学作用是一致的，与给药时间无关。然而，这里描述的研究表明，这种假设可能是无效的或不适当的。目前的发现不仅对未来的实验设计和实验数据的解释很重要，而且对影响骨吸收的药物的有效使用也很重要。

In the present study, the significance of the diurnal fluctuation of Ca metabolism, especially of the bone resorbing activity in rats, was discussed in relation to the administration of blockers of bone resorption. Under physiological condition, serum Ca, Ca transfer into bone and Ca release from bone followed diurnal rhythms in rats. The magnitude of the effects of blockers of bone resorption also varied diurnally depending on the time of drug administration, which indicates that the sensitivity of the target site (bone resorption process) to the drug also varied diurnally. Thus, it appears that if a blocker of bone resorption is administered during active bone resorption, it has a large effect, and if it is given during a period of less active bone resorption, its effect is diminished. In the field of Ca metabolism, the timing of drug administration or experimental method has thus far been based more frequently on the traditional homeostatic hypothesis. The homeostatic hypothesis implies that the pharmacological and toxicological effects of chemical agents are uniform, and are independing of the timing of administration. However, the studies described here have shown that this hypothesis may be invarid or inappropriate. The present findings should prove to be important not only in future experimental design and in the interpretation of experimental data, but also in the efficacious use of drugs which affect bone resorption.