Teriparatide, Vitamin D, Cinacalcet, Sevelamer

 Unlike BPs, raloxifene, denosumab, and calcitonin video (which block bone resorption),
these agents increase bone formation and bone mineral density
 Osteoblasts are responsible for depositing hydroxyapatite into the bone’s organic matrix
 Osteoblasts are activated by teriparatide and vitD   bone mineral density
 Osteoclasts are indirectly activated by teriparatide and vitD   bone resorption/turnover
 Bone resorption by osteoclasts leads to the release of Ca & P into blood
 High serum Ca levels act directly on parathyroid gland to inhibit PTH production & secretion
o There is a calcium-sensing receptor on parathyroid gland that responds to increased
serum Ca levels
 PTH stimulates osteoblasts to release RANKL  RANKL binds to RANK (on osteoclast
surface)   osteoclast differentiation & activity   bone resorption
 PTH stimulates maturation of osteoblasts   bone formation
 Although bone resorption & formation are both enhanced by PTH, the net effect of
endogenous PTH is to  bone resorption
 At the kidney, PTH increases Ca reabsorption (& increases phosphate excretion)
o Net effect of PTH: Ca, P
 Third way by which PTH  serum Ca levels is by  1,25-dihydroxyvitamin D (calcitriol)
o PTH increases activity of 1-hydroxylase in kidney   calcitriol production
 Teriparatide (recombinant PTH) in low & intermittent doses   bone formation
o Intermittent doses of teriparatide stimulates maturation of osteoblasts   bone
formation
o Can be used to treat osteoporosis (increase bone density)
o At the kidney, teriparatide  Ca reabsorption and P excretion (this gets more Ca into
the circulation)
o teriparatide also  activity of 1-hydroxylase in the kidney   calcitriol
 Vitamin D3 (cholecalciferol) is obtained via dairy products or UVB radiation in sunlight
 Vitamin D2 (ergocalciferol) is obtained via plants
 Steps for converting vitamin D2 or D3 into active vitamin D (calcitriol):
o 25-hydroxylase in liver converts vitamin D  25-hydroxyvitamin D (calcidiol)
o 1-hydroxylase in kidney converts 25-hydroxyvitamin D (calcidiol)  1,25-
dihydroxyvitamin D (calcitriol); this step is stimulated by PTH
 Calcitriol stimulates reabsorption of Ca and P in the kidney
 Calcitriol also stimulates intestinal absorption of Ca and P
 Like PTH, calcitriol also stimulates osteoblasts to release/express RANKL  activates
osteoclasts
 Calcitriol feeds back to parathyroid gland to inhibit PTH production
 Like PTH, calcitriol stimulates maturation of osteoblasts   bone formation
 Calcitriol can be used to treat osteoporosis
 Calcitriol can be useful in CKD to prevent hypocalcemia (note: must give this active form of
vitD here opposed to ergo/cholecalciferol since CKD kidney has difficulty converting inactive
vitD  active vitD)
 Topical vitD can be used to treat psoriasis (inhibits keratinocyte proliferation)
 Calcitriol is useful in the long-term management of hypocalcemia (eg, hypoparathyroidism)
o Note that vitD2 &vitD3 would be less effective in a hypoparathyroid pt since PTH is
important in activating vitD in the kidney
o Note: thyroid surgery can  hypoparathyroidsm and hypocalcemia
o Hypocalcemia can cause paresthesias, muscle cramps, trismus, tetany, and
potentially even seizures
 Teriparatide and vitD therapy can cause hypercalcemia
 Cinacalcet (a calcimimetic) activates the calcium sensing receptor on the parathyroid gland
  PTH production (essentially tricking gland that there is a lot of Ca around)
o Cinacalcet is useful in the treatment of hypercalcemia d/t hyperparathyroidism
(primary or secondary hyperparathyroidism)
 Sevelamer – non-absorbable phosphate-binding polymer that decreases P absorption in GIT
o Useful in the treatment of hyperphosphatemia d/t CKD