Effects of 24r,25-dihydroxyvitamin D3 in combination with 1α-hydroxyvitamin D3 in predialysis renal insufficiency: Biochemistry and histomorphometry of cancellous bone

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Abstract
The effect of combined administration of 24R,25‐dihydroxyvitamin D3 (24,25‐(OH)2D3) and 1α‐hydroxyvitamin D3 (1α‐(OH)D3) was studied in 24 non‐dialyzed patients with chronic renal insufficiency (CRI), matched pair‐wise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1α‐(OH)D3 (mean dose 0.55 μg daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1α‐(OH)D3 alone (Group A) or with 1α‐(OH)D3 plus a high dosage of 24,25‐(OH)2D3 (50 μg orally, twice weekly) (Group B). Histomorphometry was performed at T0 T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.
Funding Information
  • Dutch Kidney Foundation ((No C83.401))
  • LEO Pharmaceuticals, Weesp, The Netherlands

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