VITAMIN-D-3 ANALOGS AND SALMON-CALCITONIN PARTIALLY REVERSE THE DEVELOPMENT OF RENAL OSTEODYSTROPHY IN RATS

We have previously established an uremic rat model which is suitable for investigating the effect of various treatment modalities on the progression of renal osteodystrophy [1]. Four months subsequent to 5/6 nephrectomy, animals were treated three times a week for 3 months with either vehicle, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], 1,25(OH)(2)D-3 + 24,25-dihydroxyvitamin D-3 [24,25(OH)(2)D-3], 1,25(OH)(2)D-3 + calcitonin (CT), or 1,25(OH)(2)D-3 + 24,25(OH)(2)D-3 + CT. At termination of the study, clinical chemistry, chemical composition, and mechanical properties of femurs, calvarial parathyroid hormone (PTH)-elicited adenylate cyclase (AC), and phospholipase C (PL-C) activities, femoral cross-sectional area, and bone histomorphometry were analyzed. The main findings were that 1,25(OH)(2)D-3 +/- 24,25(OH)(2)D-3 treatment enhanced elasticity as well as time to fracture at the femoral metaphysis. CT potentiated the increase in elasticity obtained by 1,25(OH)(2)D-3 +/- 24,25(OH)(2)D-3 treatment. Only 24,25(OH)(2)D-3 administration rectified the supernormal PTH-stimulated uremic bone AC, and only 1,25(OH)(2)D-3 medication normalized the diminished CT-elicited AC. The obliterated uremic bone PTH-sensitive PL-C was fully normalized by all drug regimens. Femoral shaft inner zone diameter was enhanced by uremia, however, all drug treatments normalized it. Ditto effect was registered with either drug treatment on the subnormal outer and inner zone widths. Histomorphometrical analyses showed that 1,25(OH)(2)D-3 administration reduced both eroded and osteoid surfaces. Most prominently, adjuvant 24,25(OH)(2)D-3 or CT administration potentiated the beneficial effect of 1,25(OH)(2)D-3 on fibrosis and osteomalacia. We assert that vitamin D-3 treatment markedly reverses the development of renal osteodystrophy, and CT potentiates the effect of vitamin D-3.