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Submitted on August 22, 2006
Accepted on May 24, 2007
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, L69 3GA, UK; Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, L69 3GE, UK; Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK
* To whom correspondence should be addressed. E-mail: drfrankjoseph{at}yahoo.co.uk.
BACKGROUND: Osteoclast resorptive activity which is known to demonstrate circadian rhythmicity is regulated by various endocrine hormones and cytokines. PTH suppresses OPG, a regulator of osteoclast activity that has recently been shown to have a circadian rhythm in healthy controls. We studied the differences in the relationship between PTH, OPG and
CTX over a 24-hour period in premenopausal women, elderly postmenopausal women and elderly men.
METHODS: Hourly peripheral venous blood samples were obtained from eighteen healthy non-osteoporotic volunteers (premenopausal women (n=6; mean age 30.2±2.2 years), postmenopausal women (n=6; mean age 68.2±2.6 years) and elderly men (n=6; mean age 68.2±2.3 years)). Plasma PTH (1-84), OPG,
CTX and calcium were measured on all samples. Cosinor analysis was performed to analyze the circadian rhythm parameters. Cross-correlation analysis was used to determine the relationship between the time series of the variables.
RESULTS: 24-h mean PTH, OPG and
CTX concentrations were significantly higher in postmenopausal women as compared to premenopausal women and elderly men (p<0.001). Significant circadian rhythms were observed for PTH (p<0.05), OPG (p<0.05) and
CTX (p<0.001) in all subjects. PTH secretion was characterized by 2 peaks in premenopausal women and elderly men and by a sustained increase in PTH concentration in postmenopausal women. OPG secretion was circadian with a day time increase and nocturnal decrease and a greater percentage decrease in OPG secretion was observed in the postmenopausal women between 1600 h and 0000 h. OPG secretion was inversely related to PTH (r=-0.4) and
CTX (r=-0.6) secretion over a 24h period.
CONCLUSION: This report confirms a circadian rhythm for circulating OPG. The nocturnal decline in circulating OPG is greater in postmenopausal women as compared to premenopausal women and elderly men. Altered PTH secretion may contribute to the OPG secretory pattern in postmenopausal women resulting in increased nocturnal bone resorption.
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