Effects of 25-hydroxycholecalciferol on bone lesions of children with terminal renal failure

Abstract

Quantitative histology was performed on serial iliac crest biopsies obtained from 14 children with terminal renal failure. A long-term study on the comparative effects of vitamin D2 and 25-hydroxycholecalciferol [25-(OH)D3], in five patients with severe lesions of osteomalacia and/or osteitis fibrosa, demonstrated the efficiency of 25 to 200 mug/day of 25-(OH)D3 and the lack of therapeutic action of 345 to 685 mug/day of vitamin D2. In nine subjects with normal roentgenograms or minimal skeletal alterations, the first biopsy taken at the beginning of intermittent hemodialysis showed evidence of defective mineralization and/or lesions of resorption. Four of these children were treated with 25-(OH)D3 (25 to 50 mug/day) and calcium supplementation orally (0.5 to 1.5 g/day); five children received calcium orally (0.5 to 0.75 g/day) alone. Aggravation of bone lesions during intermittent hemodialysis was observed in patients treated with calcium supplements alone. In subjects who were given 25-(OH)D3, mineralization improved and marrow fibrosis disappeared. However, as the two groups of patients were different in composition and in the manner in which they were treated, it is difficult to state whether the beneficial effects observed were solely attributable to 25-(OH)D3 administration. 25-(OH)D3 therapy induced severe intoxication in two patients. A rise in plasma calcium concentration to 11.0 to 11.5 mg/100 ml was observed in two other patients. It is concluded that: a) pharmacologic doses of 25-(OH)D3 are highly effective in healing bone lesions of children with terminal renal failure; b) such treatment requires strict clinical surveillance as 25-(OH)D3 intoxication may occur even in anephric patients.

Extraction of Vitamin D Metabolites by Bones of Normal Adult Dogs

“…Although the relationship between vitamin D and bone is well established in treatment studies (18)(19)(20)(21), the actual handling of the different vitamin D metabolites by bone has not been clarified. Most studies on this topic have been performed in either animals with vitamin D deficiency or in fetal cell preparations often from the rat calvaria (1-3, 7, 8).…”

Serum 1,25-DihydroxycholecalciferoI in Anephric, Haemodialyzed and Kidneytransplanted Patients

“…It is well documented that large doses of vitamin D [17] and 25-OHD.t [15,18,19] are able to improve the uraemic bone lesions in patients with re maining kidney tissue. This might be due to an increased production of l,25-(OH)aD3 induced by a mass action effect of 25-OHÜ3 on the I-hydroxylase system in the damaged kidney, or perhaps on the production of other vitamin D metabolites such as 24,25-dihydroxycholecalciferol.…”

The effect of vitamin D2 on hypocalcemia in patients under chronic hemodialysis.

“…However, Witer et al (1976) reported that in a non-dialysed girl (14 years of age) with chronic renal failure, 13,000-28,000 IU/day of VD2 supplementation for 5 months were not effective for the correction of hypocalcemia and renal bone diseases.…”

“…Major symptoms related to these abnormal calcium metabolism in long-term dialysis are as follows: osteomalacia, and other complications of secondary hyperpara thyroidism (hypercalcemia, metastatic calcification, and pruiritis). It is well recognized that these abnormal calcium metabolism is primarily due to defective formation of 1, 25 We have treated patients by hemodialysis using dialysate containing a fixed calcium concentration (3.5 mEq/liter) since 1972. To correct negative calcium balance in patients on chronic hemodialysis, VD2 has been used in our hemodialysis unit.…”