Circadian and circatrigintan changes in osteoblastic activity assessed by serum osteocalcin. Physiological and methodological aspects.

The author has shown the existence of reproducible circadian changes and significant variation during the circatrigintan rhythm in the osteoblastic marker, serum osteocalcin. The author find that appropriate exploratory data analyses are important and often imperative tools in the demonstration of these low frequent rhythms, and the effects of intervention. The metabolism of osteocalcin needs further investigation since it is essential to consider the kinetic of serum osteocalcin in the interpretation of data. However, based on current knowledge of the kinetics of serum osteocalcin, and the variation in other osteoblastic markers, the author conclude that the results are indicative of the existence of biological rhythms in osteoblastic activity rather than changes in metabolic clearance. The physiological aspects on the circadian rhythm are that osteoblastic activity peaks during the early night and decrease in the morning in both men and women. The circadian osteoblastic activity is relatively stable during seasons and apparantly not acutely related to sleep. Modest doses of alcohol decrease serum osteocalcin within few hours but the circadian rhythm is not different in smokers compared with non-smokers. There are evidences for endogeneous cortisol as regulator of the osteocalcin rhythm especially by mediating the morning decrease in osteocalcin. Osteocalcin synthesis is not completely blocked by glucocorticoids since the effect is blunted by administration of 1,25-(OH)2D3. Although serum osteocalcin may respond to acute doses of several other osteotrophic hormones, it is doubtfull whether endogeneous PTH, 1,25-(OH)2D3, sex hormones, or growth hormone play any role as acute regulators of the circadian osteocalcin rhythm. The circatrigintan rhythm is characterized by highest levels of serum osteocalcin during the luteal phase. There is a significant cross correlation with the follicular increase in serum estradiol but the regulation of serum osteocalcin during the ovulatory cycle remains to be settled. The results, however, support the interaction between sex hormones and bone metabolism. The practical implications are that blood sampling for determination of serum osteocalcin should be strictly standardized with regard to the time of the day and the time since last medication or intervention with factors that may affect osteoblastic activity.