OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING:17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS:176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS:Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS:132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls givenplacebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.
RCT Entities:
OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS:Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.
Authors: W Pluskiewicz; P Adamczyk; B Drozdzowska; K Szprynger; M Szczepańska; Z Halaba; D Karasek Journal: Osteoporos Int Date: 2003-04-16 Impact factor: 4.507