Alterations in serum and urine parameters reflecting bone turnover in uremic patients during treatment with 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3.
Previously we demonstrated that bone resorption in uremic patients appears to be related to increased serum parathyroid hormone (PTH) and to osseous PTH-stimulated adenylate cyclase (AC), the latter being inversely correlated to serum 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]. In this study, we continue to examine the possible modulatory role of vitamin D3 analogs on the progression of the uremic condition. Four groups of predialytic uremic patients received oral administrations of CaCO3 (control), 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] (0.25-0.50 microgram/day), 24,25(OH)2D3 (15 micrograms/day) or a combination of the two vitamin D3 analogs for 6 months. In the treatment groups receiving single or combined therapy, respectively, the low pretrial serum levels of 1,25(OH)2D3 were raised (p < 0.05) within upper normal range, while the serum levels of 24,25(OH)2D3 were increased (p < 0.05) to twice the average physiological level. Neither regimens alone resulted in significant changes in serum levels of calcium of PTH. 1,25(OH)2D3 moderately hampered bone formation by reducing serum alkaline phosphatase (ALP) by some 15%. 24,25(OH)2D3 significantly decreased (p < 0.01) bone PTH-AC up to 98% after 2 and 6 months. However, no correlation was found between serum 24,25(OH)2D3 and the bone turnover parameters serum ALP, serum osteocalcin and urine hydroxyproline/creatinine ratio. These parameters were all positively correlated (p < 0.05) to serum PTH, indicating an on-going bone turnover. These biochemical events strongly indicate that 24,25(OH)2D3 may retard the PTH-dependent progression in bone demineralization occurring in uremic patients. This effect is apparently not reduced by concomitant 1,25(OH)2D3 administration.
Institute of Medical Biochemistry, University of Oslo, Norway.
B M
BM
Mortensen
J O
JO
Gordeladze
P T
PT
Lyngdal
H P
HP
Aarseth
K M
KM
Gautvik
D015650:24,25-Dihydroxyvitamin D 3 / Q000008:administration & dosage / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood / Q000652:urine; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D014511:Uremia / Q000188:drug therapy / Q000378:metabolism*
D010281:Parathyroid Hormone; D010710:Phosphates; D015675:Osteocalcin; D015650:24,25-Dihydroxyvitamin D 3; D000469:Alkaline Phosphatase; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium