title: A calcium homeostasis model: orchestration of fast acting PTH and calcitonin with slow calcitriol.
abstract: Calcitriol is in plasma bound to transcalciferin and this results in a long calcitriol half-life in plasma (5-12h). Abundance of bound calcitriol molecules prevents the exact and quick control of its effects and makes it an inert regulator with a time lag between the changes of calcitriol synthesis and its effect on peripheral tissues. The added regulatory inertia is here defined as: calcitriol(bound)/calcitriol(free) and it approaches value of 99. Estrogens increase transcalciferin levels. It is possible that the estrogen-induced increase in the total calcitriol plasma pool makes calcitriol effects even more inert, augmenting and prolonging the calcitriol effects and thus improving calcium balance in women. Since calcitriol synthesis in kidneys depends on the PTH level, it can be assumed that the size of the total calcitriol pool in plasma reflects more the average PTH secretion during previous hours, than the high or low peaks of PTH secretion in the same period. In other words, one or more PTH tides of short duration are followed with a late calcitriol tide that lasts for hours, and even longer lasting rise in calcitriol effects. Bone integrity depends also on the cortisol level. A possible speculation is that the main result of all profound bone effect of hypecortisolemia, might be reduction of the bone amino acids uptake, thus allowing redistribution of available proteins. Both PTH and calcitriol prevent dangerous hypocalcemia. PTH is quick in mobilizing bone calcium, while calcitriol tends to increase absorption of dietary calcium. In case of low or no dietary calcium, calcitriol mobilizes bone calcium and thus increase PTH initiated demineralization. In the case of calcium abundance, increased plasma calcium reduces PTH levels. Calcitriol plasma level (reflecting previous PTH surges) can induce both calcium absorption and bone demineralization. This two-blade action is tuned by calcitonin that reduces osteoclastic bone resorption, allowing bone deposition of abundant calcium. An overnight fast with a reduced absorption of dietary calcium, might decrease plasma calcium below the regulatory set point, inducing an increase in PTH secretion. Increased average nighttime PTH secretion induces more calcitriol to be synthesized in kidneys. The resultant late calcitriol morning and daytime tide would stimulate calcium absorption from gut, or from bone, depending on the availability of dietary calcium. Due to the described time lag in calcitriol effects, increased calcium absorption might continue during daytime, regardless of the plasma calcium level. If plasma calcium is above the set point, calcitonin will allow excess calcium to deposit in bones. A speculation based on this model is that it might be more efficient to avoid calcium rich food for dinner or supper, and to administer calcium supplementation in the morning, during the calcitriol tide.
authors.affiliation: Osijek Medical Faculty, Osijek, Croatia. sven@jware.hr
authors.forename: Sven
authors.initials: S
authors.lastname: Kurbel
authors.forename: Radivoje
authors.initials: R
authors.lastname: Radić
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Kotromanović
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Puseljić
authors.forename: Boris
authors.initials: B
authors.lastname: Kratofil
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000097:blood / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002136:Calcium, Dietary / Q000378:metabolism; D002940:Circadian Rhythm; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000378:metabolism*
chemical_list: D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D002116:Calcitonin; D002117:Calcitriol; D002118:Calcium