Secretion Patterns of Circulating Osteoprotegerin and Response to Acute and Chronic Energy Deprivation in Young Healthy Adults

Osteoprotegerin (OPGN) is a bone-remodeling marker that is associated with various metabolic and vascular complications. Cross-sectional studies in humans have demonstrated an inverse association between leptin, a marker of energy sufficiency, and OPGN. The physiology of OPGN has not been fully elucidated to date. We thus aim to elucidate 1) whether OPGN levels exhibit any gender dimorphism or day/night secretion pattern; and 2) whether there is any effect of acute and/or chronic energy deprivation on its circulating levels and whether such effects are mediated through leptin.Study A: To evaluate OPGN secretion patterns and OPGN response to acute energy deprivation, we studied 12 healthy subjects under three different conditions for 72 h-in the isocaloric fed state, and during a fasting state with administration of either placebo or metreleptin in replacement doses. Blood samples were obtained every 15 min and pooled hourly during the last 24 h of the study. Study B: To evaluate the effect of chronic energy deprivation on OPGN secretion, we measured its levels in 14 obese subjects before and during weight loss after bariatric surgery.OPGN levels exhibited a statistically significant (P0.01), albeit clinically limited in magnitude, day/night variation pattern in both genders (R(2) = 14.68%; 10.7-14.8% reduction with lower levels around 1600-1800 h; P0.01). Males had lower OPGN levels compared to females (1.81 ± 0.04 vs. 3.65 ± 0.07 pmol/liter; P0.001). Three days of fasting with either placebo or metreleptin administration did not change OPGN levels. OPGN levels did not change during bariatric surgery-induced weight loss.OPGN levels are lower in men and exhibit a statistically significant, albeit clinically limited in magnitude, day/night secretion pattern. Neither acute nor chronic energy deprivation leading to significant weight loss has any effects on OPGN levels. Nomenclature Comment: Use of the terms "circadian" and "day/night variation" is meant as follows: Circadian pattern is a functional term that implies a rhythm that has been proven to be regulated by the innate circadian apparatus (anatomical and/or molecular). Conversely, day/night variation pattern is a descriptive term that refers to serum levels that vary during a day, usually in a periodic fashion. It is not known whether this variation is an innate property of the organ that secretes this hormone or whether it is determined by exogenous factors.