In understanding the hormonal regulation of calcium and phosphorus homeostasis, it is important to appreciate that bone tissue is quite dynamic, in terms of both the metabolic activity of the various cell populations present and with regard to the kinetics of mineral flux into and out of the several bone compartments. As summarized in Figure 9-1, there are three functional, but not anatomical, compartments of bone mineral; they are comprised from the total ~1 million milligrams of calcium and ~500,000 mg of phosphate that are incorporated into bone mineral of adult males. The Ca2+ and H2PO4−/HPO42− precipitates on the sur face of the extracellular organic bone matrix as the mineral calcium hydroxyapatite, which has the empirical formula of [Ca2+10(PO43−)6(OH−)2]. The functional Ca2+ compartments present in bone can be identified on the basis of radioactive tracer studies (utilizing either radioactive 45Ca2+ or 47Ca2+). These compartments include the following: (a) the rapid-exchange bone mineral compartment (~20,000 mg/day); (b) a slow-exchange compartment (~300 mg/day of Ca2+); and (c) a hormonally regulated compartment (~300 mg/ day of Ca2+ via bone resorption and ~300 mg/day of Ca2+ via bone accretion).
The term rapid-exchange implies the capability of a rapid (on a minute-by-minute basis) loss and gain of calcium via chemical dissolution from the calcium hydroxyapatite followed immediately by reprecipitation.
Thus in one day, ~20,000 mg of calcium leaves the bone and another ~20,000 mg returns to the bone in this rapid-exchange “compartment.” In the slow-exchange compartment, ~300 mg of calcium leave via a slower chemical dissolution and then ~300 mg of calcium return via a reprecipitation process into the bone’s calcium hydroxyapatite. Similarly, the third compartment is comprised of the stable bone mineral (calcium hydroxyapatite) that in the adult male is composed of approximately 1 kg (1 million milligrams) of calcium. However, the “stable bone mineral” compartment is not biologically inert. Both the accretion and resorption processes of the third compartment are those that are mediated on a minute-by-minute basis by the hormonal regulators of calcium metabolism [PTH, calcitonin (CT) and 1α,25(OH)2D3], whereas the rapid and slow exchange pools largely represent chemical equilibria between the bone and the bathing extracellular fluids.
In a normal adult, a remodeling of the stable bone mineral is occurring continuously throughout life, such that, on any given day, approximately 300 mg of calcium is resorbed and another 300 mg of calcium is replaced by accretion. Thus, in the normal state there is a balance in the extent of daily bone resorption and bone accretion, leading to no net change in total skeletal calcium content.
