The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms 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 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms 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.
A total of 33 women with postmenopausal osteoporosis were matched pairwise by age, years since menopause, and body mass index and randomized to receive either cyclic estrogen-progestagen replacement treatment (group 1) or the same treatment plus nandrolone decanoate (ND; group 2). Both groups were treated during 3 years and subsequently followed for another year off treatment. A year after cessation of the treatment the distal forearm bone mineral content in group 2 was significantly higher than that in group 1. Bone mass measurements in the axial skeleton already showed a significant difference in favor of group 2 after 3 years treatment, which persisted during the year off treatment. The decline in lumbar bone mineral mass and density in the 1 year off treatment was similar in both groups. Correction for body mass did not change these results. Bone turnover parameters did not show significant differences between the two groups after cessation of treatment. A higher muscle mass, induced by ND, could partly explain the differences between the groups since even 1 year after treatment was stopped an increased serum creatinine level was still observed in group 2.
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