PTH and vitamin D

calcitonin, glucocorticoids, and estrogens play secondary roles

acts on membrane G-protein-coupled receptors to increase cAMP in bone and renal tubular cells

in kidney: inhibits excretion of Ca2+, promotes PO4 excretion; stimulates production of active vitamin D metabolites

in bone: promotes bone turnover by increasing activity of osteoclasts and osteoblasts (osteoclast indirectly activated by PTH via osteoblast formation of RANK ligand (RANKL) - part of TNF cytokine family)

synthesis and secretion of PTH is primarily regulated by the serum concentration of free ionized calcium - drop in free ionized calcium stimulates PTH release

secondary Vitamin D metabolites play secondary role --> inhibit PTH synthesis

recombinate truncated form of PTH

given IV for tx of osteoporosis

• - fat soluble vitamin
• - active metabolites are formed in the liver and kidney:

* 25-hydroxyvitamin D

* calcifediol

* 1,25-dihydroxyvitamin D (calcitriol)

• - Renal synthesis of active metabolites of Vit D stimulated by PTH and FGF23 (produced by osteoclasts and osteoblasts)
• active Vit D metabolites cause net increase in serum concentrations of calcium and phosphate by increasing intestinal absorption and bone resorption and decreasing renal excretion
• inhibits PTH secretion DIRECTLY and INDIRECTLY (by increasing serum Ca)

-

Vit D required for normal bone mineralization

= Ricket's in kids

= osteomalacia in adults

deficiency states

intstinal osteodystrophy

chronic kidney or liver dz

hypoparathyroidism

nephrotic syndrome

also used in combination with calcium supplementation (prevent and treat osteoporosis in older women)

topical formation for psoriasis

2 forms of Vitamin D

available as oral supplements

commonly added to dairy products and other foods

active form of Vitamin D

required in patients with conditions that impair vitamin D activation (chronic kidney dz, liver dz, hypoparathyroidism)

in chronic kidney dz, calcitriol reduces PTH levels, corrects hypocalcemia, and improves bone disease, but it can also result in hypercalcemia and hypercaliuria through direct effects on intestinal, bone, and renal handling of calcium and phosphate

prodrug that is converted in the liver to 1,25-dihyrdroxyvitain D

causes less hypercalcemia and less hypercalciuria than calcitriol

used in tx of secondary hyperparathyroism due to chronic renal dz

19-nor-1,25-dihydroxyvitamin D2

analog of calcitriol

causes less hypercalcemia and less hypercalciuria than calcitriol

approved for tx of 2ary hyperparathyroidism due to chronic renal dz

analog of calcitriol

causes less hypercalcemia and less hypercalciuria than calcitriol

used for tx of psoriasis

hypercalcemia

hyperphosphatemia

hypercalciuria

secreted by the thyroid gland

decreases serum calcium and phosphate by inhibiting bone resorption and inhibiting renal excretion of these minerals

bone formation is ultimately reduced

USE: in conditions where an actue reduction of serum calcium is needed (ex: Paget's dz and hypercalcemia)

also approved for tx of osteoporosis (but not as effective)

salmon calcitonin used because has longer half-life and greater potency

admin = injection or nasal spray

selective estrogen receptor modulators (SERMs)

prevent or delay bone loss in postmenopausal women

inhibition of PTH-stimulated bone resorption

inhibit bone mineral maintenance = chronic systemic use is common cause of osteoporosis in adults

but they are useful in intermediate-term tx of hypercalcemia

(alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, and zoledronic acid)

short-chain organic polyphosphate compounds that reduce both the resorption and the formation of bone by an action on the baasic hydroxyapatite crystal structure

effects on vit. D production and calcium absorptions from GI tract

direct effects on osteoclasts

used to manage hyper calcemia associated with some malignancies and to treat Paget's dz

chronic uses of this for osteoporosis tx (increases bone density and reduces fractures)

calcimimetics

lowers PTH by activating the calcium-sensing receptor in parathyroid gland

oral tx for secondary hyperparathyroidism in chronic kidney dz

tx for hypercalcemia in pts with parathyroid carcinoma -

toxicities include hypocalcemia and adynamic bone dz (profound decr. bone cell activity)