Non-nutritional rickets: Approach, precision medicine, and outcomes

Table 6 Comparative pharmacology of vitamin D preparations

Parameter	Cholecalciferol (Vitamin D3)	Calcidiol (25-hydroxyvitamin D3)	Alfacalcidol (1α-hydroxyvitamin D3)	Calcitriol (1,25-dihydroxyvitamin D3)
Biochemical form	Native vitamin D3	25-hydroxylated form	Synthetic 1α-hydroxylated analogue	Fully active hormonal form
Activation required	Hepatic + renal hydroxylation	Renal hydroxylation only	Hepatic hydroxylation only	None
Dependence on organ function	Liver and kidney dependent	Kidney dependent	Liver dependent	Independent of liver and kidney activation
Onset of action	Slow	Intermediate	Rapid	Rapid
Half-life	Long (weeks)	Intermediate (2-3 weeks)	Short (hours to days)	Very short (4-6 hours)
Mechanism of action	Prohormone	Circulating precursor	Converted to calcitriol in liver	Direct activation of vitamin D receptor
Clinical indications	Nutritional vitamin D deficiency	Malabsorption, obesity, liver disease	Chronic kidney disease, hypoparathyroidism	Severe hypocalcemia, CKD, hypoparathyroidism, VDDR
Risk of hypercalcemia	Low	Moderate	High	Highest
Monitoring requirements	Minimal	Intermittent	Frequent monitoring required	Close monitoring required

CKD: Chronic kidney disease; VDDR: Vitamin D dependent rickets.