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The Circadian Rhythm of Osteoprotegerin and Its Association with Parathyroid Hormone Secretion

Departments of Diabetes and Endocrinology (F.J., A.M.A., J.P.V.) and Nuclear Medicine (S.V.), Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom; Department of Clinical Biochemistry and Metabolic Medicine (B.Y.C., B.H.D., W.D.F.), Royal Liverpool University Hospital, Liverpool L69 3GA, United Kingdom; and Human Bone Cell Research Group (J.A.G.), Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool L69 3GE, United Kingdom

Address all correspondence and requests for reprints to: Dr. Franklin Joseph, Department of Diabetes and Endocrinology, Link 7C, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, United Kingdom. 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 osteoprotegerin (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 type I collagen C-telopeptide (ßCTX) over a 24-h period in premenopausal women, elderly postmenopausal women, and elderly men.

Methods: Hourly peripheral venous blood samples were obtained from 18 healthy non-osteoporotic volunteers: premenopausal women (n = 6; mean age, 30.2 ± 2.2 yr), postmenopausal women (n = 6; mean age, 68.2 ± 2.6 yr), and elderly men (n = 6; mean age, 68.2 ± 2.3 yr). Plasma PTH (1–84), OPG, ßCTX, 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: The 24-h mean PTH, OPG, and ßCTX concentrations were significantly higher in postmenopausal women as compared with premenopausal women and elderly men (P < 0.001). Significant circadian rhythms were observed for PTH (P < 0.05), OPG (P < 0.05), and ßCTX (P < 0.001) in all subjects. PTH secretion was characterized by two peaks in premenopausal women and elderly men and by a sustained increase in PTH concentration in postmenopausal women. OPG secretion was circadian with a daytime increase and nocturnal decrease, and a greater percent decrease in OPG secretion was observed in the postmenopausal women between 1600 and 2400 h. OPG secretion was inversely related to PTH (r = –0.4) and ßCTX (r = –0.6) secretion over a 24-h period.

Conclusion: This report confirms a circadian rhythm for circulating OPG. The nocturnal decline in circulating OPG is greater in postmenopausal women as compared with premenopausal women and elderly men. Altered PTH secretion may contribute to the OPG secretory pattern in postmenopausal women resulting in increased nocturnal bone resorption.