As if all this talk about cortisol, circadian rhythm, and dosing isn't enough to drive you crazy....here is some information suggesting that big nighttime doses can contribute to bone loss. Apparently, the secretion of osteocalcin---a measure of bone formation---also follows a circadian pattern, being highest at around 1 AM.  High doses of steroids given at night were shown to decrease circulating doses of osteocalcin, demonstrating a possible connection between timing of doses and bone loss.  This study was done on baby piglets---which are supposed to respond like humans in their processing of minerals---and uses only dexamethasone, which is much more potent than HC, but the conclusion was that high doses in the morning and low doses at night were most conducive to normal growth.  More food for thought.....

http://www.pedresearch.org/cgi/content/full/48/2/238

".....Osteocalcin, a sensitive bone formation marker, was reported previously in adults and children to have a zenith at night and nadir in the morning (17, 18)....In children and adults, a circadian rhythm in bone formation paralleled that observed for circulating cortisol .....Therefore, plasma cortisol may also regulate the circadian rhythm in bone formation during infancy......

.....By using a low evening dosing regimen with high DEX dose (70%) in the morning and low DEX dose (30%) in the evening, we demonstrated that corticosteroid-induced suppression of bone formation as determined by plasma osteocalcin and growth as determined by body weight were partially attenuated. Thus, the low evening dose of DEX may allow for a more normal physiologic milieu of growth factors to be operational during the night.....

^{.......We conclude that a plasma osteocalcin zenith exists at night in early life. High DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth. This physiologic approach to steroid therapy should be studied.......to determine whether the desired therapeutic efficacy can be achieved while at the same time minimizing the negative effects on growth and bone turnover. "}