ALTERATIONS IN SERUM AND URINE PARAMETERS REFLECTING BONE TURNOVER INUREMIC PATIENTS DURING TREATMENT WITH 1,25-DIHYDROXYVITAMIN-D(3) AND 24,25-DIHYDROXYVITAMIN-D(3)

Previously we demonstrated that bone resorption in uremic patients app ears to be related to increased serum parathyroid hormone (PTH) and to osseous PTH-stimulated adenylate cyclase (AC), the latter being inver sely correlated to serum 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]. In this study, we continue to examine the possible modulatory role of vit amin D3 analogs on the progression of the uremic condition. Four group s of predialytic uremic patients received oral administrations of CaCO 3 (control), 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] (0.25-0.50 mug/da y), 24,25(OH)2D3 (15 mug/day) or a combination of the two vitamin D3 a nalogs for 6 months. In the treatment groups receiving single or combi ned therapy, respectively, the low pretrial serum levels of 1,25(OH)2D 3 were raised (p < 0.05) within upper normal range, while the serum le vels of 24,25(OH)2D3 Were increased (p < 0.05) to twice the average ph ysiological level. Neither regimens alone resulted in significant chan ges in serum levels of calcium or PTH. 1,25(OH)2D3 moderately hampered bone formation by reducing serum alkaline phosphatase (ALP) by some 1 5%. 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 se rum 24,25(OH)2D3 and the bone turnover parameters serum ALP, serum ost eocalcin and urine hydroxyproline/creatinine ratio. These parameters w ere all positively correlated (p < 0.05) to serum PTH, indicating an o n-going bone turnover. These biochemical events strongly indicate that 24,25(OH)2D3 may retard the PTH-dependent progression in bone deminer alization occurring in uremic patients. This effect is apparently not reduced by concomitant 1,25(OH)2D3 administration.