The exchange of calcium between extracellular fluid and bone can be considered kinetically (see Plate 2-28). Through a slow phase of bone formation and resorption, approximately 1000 mg/day of calcium is exchanged between bone and extracellular fluid; this represents approximately one tenth of 1% of the total calcium reserve (1000 to 1200 g). Most of the calcium in bone does not readily diffuse into the extracellular compartment but must be mobilized by endocrineregulated, cell-mediated bone resorption. There is no known sustained biologic process by which the body can remove just the mineral component of bone. Thus, when the body needs to withdraw calcium from its mineral reserves, it can do so only by resorbing bone (mineral component plus organic matrix). Through the process of coupling, bone formation increases and osteoblasts are stimulated to fill in the resorption defect, although this repair may not be complete in the elderly.

Endocrine-mediated bone formation and bone resorption involve more than the stimulation of existing differentiated bone cells; these processes are dependent on the transformation of undifferentiated stem cells in both osteoblast and osteoclast lineages. Thus, bone formation and bone resorption are contingent not only on the metabolic activity of each cell but also on the recruitment of new cells to the job.

The major function of calcitonin, a hormone secreted by the parafollicular cells of the thyroid gland, is to inhibit osteoclastic bone resorption in response to elevated serum calcium levels. The biologically active vitamin D metabolite 1,25(OH)₂D regulates intestinal absorption of calcium and phosphate and activates bone resorption by stimulating the recruitment of osteoclast precursors (preosteoclasts). There is evidence that 1,25(OH)₂D also stimulates the recruitment of osteoblast precursors. Conversion of 25-hydroxyvitamin D, or 25(OH)D, to 1,25(OH)₂D in the kidney is controlled by the enzyme 25-hydroxyvitamin D-1α-hydroxylase, or 25(OH)D-1α-OH_ase, and stimulated maximally by increased serum PTH and decreased serum phosphate levels.

Efficient gastrointestinal absorption of calcium depends primarily on daily calcium intake, vitamin D status, and age. Because the major storage form of vitamin D is 25(OH)D, the serum level of 25(OH)D is an excellent indicator of the body’s total vitamin D reserves. With the vitamin D axis intact, efficiency of calcium absorption increases if calcium intake decreases. Some calcium secreted into the intestine is absorbed, but much of it passes into the stool as unabsorbed calcium.

The kidney filters about 8000 mg of calcium daily and, under the influence of PTH, reabsorbs more than 95%. For each additional gram of calcium ingested, only about 50 mg of additional calcium appears in urine. Thus, the urinary calcium level is better determined by the rate of calcium absorption by the intestine than by the amount of calcium ingested.