161- Why is cholecalciferol/ergocalciferol and not calcitriol used for the treatment
of vitamin D deficiency?
Supplementation with cholecalciferol/ergocalciferol results in normalization of
25(OH)D levels, which is the precursor for 1,25 (OH) 2 D. Therapy with calciferol
results in regulated synthesis of 1,25(OH) 2 D (calcitriol) due to exquisite regulation
of 1α-hydroxylase activity in PCT. In addition, 25(OH)D may also have direct
effects on vitamin D receptor. Therapy with calcitriol does not normalize 25(OH)
D levels, is expensive, requires frequent administration (as it has a half-life of 4h),
and has the risk of iatrogenic hypercalcemia. Hence, cholecalciferol/ ergocalcif-
erol is used for the treatment of vitamin D deficiency, rather than calcitriol. - What are the indications for therapy with calcitriol?
1,25(OH) 2 D is synthesized from 25(OH)D by the enzyme 1α-hydroxylase,
which is present in the proximal convoluted tubule of the kidney. The activity of
1 α-hydroxylase is stimulated by PTH and inhibited by FGF-23. Therefore, dis-
orders associated with impaired 1α- hydroxylase activity or deficient secretion/
action of PTH or increased FGF-23 require calcitriol therapy. These include
hypoparathyroidism, pseudohypoparathyroidism, advanced stage chronic kid-
ney disease, and hypophosphatemic osteomalacia. In addition, vitamin
D-dependent rickets type 1 (inactivating mutations of 1α-hydroxylase) and type
2 (vitamin D receptor defects) are indications for calcitriol therapy (Fig. 5.13).a bFig. 5.13 (a) A 15-year-old boy with genu valgum and left knee joint deformity due to stage V
chronic kidney disease (renal osteodystrophy). (b) Bowing of both forearms (L>R) in the same
patient. Note the presence of A–V fistula
5 Rickets–Osteomalacia