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

本文讨论了大鼠钙代谢尤其是骨吸收活动的昼夜波动与应用骨吸收阻滞剂的关系。在生理条件下，大鼠血钙、钙向骨内转运和骨钙释放遵循昼夜节律。骨吸收阻滞剂的作用大小也随给药时间的不同而不同，这表明靶点(骨吸收过程)对药物的敏感性也随药物的日变化而变化。因此，似乎如果在活跃的骨吸收期间使用骨吸收阻滞剂，它有很大的作用，而如果在骨吸收较不活跃的时期使用，它的作用就会减弱。在钙代谢领域，到目前为止，给药的时机或实验方法更多地基于传统的体内平衡假说。动态平衡假说意味着化学制剂的药理和毒理作用是一致的，并且不依赖于给药的时间。然而，这里描述的研究表明，这一假设可能是不恰当的或不合适的。目前的发现不仅在未来的实验设计和对实验数据的解释中被证明是重要的，而且在影响骨吸收的药物的有效使用方面也被证明是重要的。

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.