Vitamin D metabolites and bone mineralization in man

A comparison was made of the biochemical and osseous effects of 25-hydroxyvitamin D3 [25(OH)D3], 1 alpha-25-hydroxyvitamin D3 [1 alpha, 25(OH)2D3], and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in adult vitamin D-deficient man. Administration of 50 micrograms/d of 25(OH)D3 for 8 weeks led to a return of the mineralization front to normal associated with a return of TmPO4/GFR to normal, an increase in serum phosphate and calcium concentrations, a fall in serum IPTH, and a rise in serum alkaline phosphatase activity. Giving 2.5 micrograms/d of 1 alpha,25(OH)2D3 did not produce these effects. Administration of 1 alpha, 25 (OH)2D3 caused an increase in intestinal calcium absorption, and a rise in serum calcium associated with a fall in serum immunoreactive parathormone (IPTH) concentrations but no sustained rise in either alkaline phosphatase, serum phosphate concentration, nor in TmPO4/GFR. Its administration caused an increase in the extent of the osteoclastic bone resorption surface but the extent of the mineralization front remained subnormal. Administration of 20 micrograms/d of 24,25(OH)2D3 caused a fall in urinary calcium excretion and in serum IPTH, and a rise in serum alkaline phosphatase, but no change in TmPO4/GFR or serum phosphate, and only a slight increase in the extent of the mineralization front. Combined treatment with 1 alpha, 25(OH)2D3 and 24,25(OH)2D3 led to a return of the mineralization front of normal even though both TmPO4/GFR and serum phosphate concentration remained low. It is concluded that 1alpha,25(OH)2D3 is not the sole biologically active metabolite of vitamin D in man. It is apparent that either 25(OH)D3 or some as yet unidentified metabolite of 25(OH)D3 stimulates the renal tubular reabsorption of calcium and phosphate, and that the subsequent rise in serum phosphate concentrations along with the direct actions of 1 alpha-25(OH)2D3, 24,25(OH)2D3, and possibly 25(OH)D3 on bone cells all participate in the restoration of normal bone formation and bone mineralization in vitamin D-deficient man.