Skip to Main Content


Calcium and phosphorus, the 2 major elements of bone, are crucial not only for the mechanical strength of the skeleton but also for the normal function of many other cells in the body. Accordingly, a complex regulatory mechanism has evolved to tightly regulate calcium and phosphate homeostasis. Parathyroid hormone (PTH), vitamin D, and fibroblast growth factor 23 (FGF23) are primary regulators (Figure 42–1), whereas calcitonin, glucocorticoids, and estrogens play secondary roles. These hormones, or drugs that mimic or suppress their actions, are used in the treatment of bone mineral disorders (eg, osteoporosis, rickets, osteomalacia, Paget’s disease), as are several nonhormonal agents.



Effects of active metabolites of vitamin D (D), parathyroid hormone (PTH), calcitonin (CT), and fibroblast growth factor 23 (FGF23) on calcium and phosphorus homeostasis. Active metabolites of vitamin D increase absorption of calcium from both gut and bone, whereas PTH increases reabsorption from bone. Vitamin D metabolites and PTH both reduce urinary excretion of calcium. In animals with vitamin D deficiency, active metabolites of vitamin D produce a net increase in bone mineralization by increasing the availability of serum calcium and phosphate. (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, 2012: Fig. 42–1.)


A. Parathyroid Hormone

Parathyroid hormone (PTH), an 84-amino-acid peptide, acts on membrane G protein-coupled receptors to increase cyclic adenosine monophosphate (cAMP) in bone and renal tubular cells. In the kidney, PTH inhibits calcium excretion, promotes phosphate excretion, and stimulates the production of active vitamin D metabolites (Figure 42–1, Table 42–1). In bone, PTH promotes bone turnover by increasing the activity of both osteoblasts and osteoclasts (Figure 42–2B). Osteoclast activation is not a direct effect and instead results from PTH stimulation of osteoblast formation of RANK ligand (RANKL), a member of the tumor necrosis factor (TNF) cytokine family that stimulates the activity of mature osteoclasts and the differentiation of osteoclast precursors.

TABLE 42–1Actions of PTH and active vitamin D metabolites on intestine, kidney, and bone.

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.