BES2005 Poster Presentations Growth and development (48 abstracts)
1Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, UK; 2Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK; 3Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK; 4Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, The University of Liverpool, Liverpool, UK.
BACKGROUD: Parathyroid hormone (PTH) is normally secreted in a circadian rhythm and modulates bone turnover through the differential stimulation of receptor activator for nuclear factor kappa-B ligand (RANKL) and suppression of osteoprotegerin (OPG), both of which are fundamental factors in regulating bone turnover. We have studied the relationship between PTH and OPG over a 24-hour period.
METHODS: Hourly peripheral venous blood samples were obtained from eight volunteers (four men and four women; mean age 56plus/minus7 years). Plasma PTH (1-84) and OPG were measured on all samples. Cosinor analysis was performed to analyze circadian rhythm parameters. Cross-correlation and Pearson's analysis was used to determine the relationship between variables and whether one time series led another. Cross-correlation analysis determines the correlation between two time series of equal length that have been paired, data point by data point, and then one of the time series is shifted by one or more time points (lag time) and the correlation process is repeated.
RESULTS: Significant circadian rhythms were observed for PTH and OPG (p < 0.001). Secretory patterns of PTH and OPG were out-of-phase during a 24 h period and maximal negative correlation between PTH and OPG (r = -0.6) was observed when PTH changes preceded OPG changes by one hour. Pearson's correlation analysis confirmed that the diurnal rhythm of PTH correlated significantly and negatively with that of OPG (r = -0.4; p < 0.03).
CONCLUSION: We have demonstrated for the first time that peripheral blood concentrations of OPG demonstrate a concerted circadian rhythm which may, in part, be regulated by the circadian changes in PTH concentration that control bone turnover on a daily basis. A significant decrease in OPG in response to increasing PTH may result in increased bone resorption by osteoclasts.