Abstract
We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established.
Publication types
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Comparative Study
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Randomized Controlled Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Bone Density Conservation Agents / adverse effects
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Bone Density Conservation Agents / pharmacology
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Bone Density Conservation Agents / therapeutic use*
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Bone and Bones / drug effects
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Bone and Bones / pathology
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Bone and Bones / physiopathology
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Calcitriol / adverse effects
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Calcitriol / pharmacology
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Calcitriol / therapeutic use*
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Calcium Carbonate / administration & dosage
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Calcium Carbonate / therapeutic use
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Chronic Kidney Disease-Mineral and Bone Disorder / drug therapy
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Chronic Kidney Disease-Mineral and Bone Disorder / etiology
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Drug Therapy, Combination
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Ergocalciferols / adverse effects
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Ergocalciferols / pharmacology
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Ergocalciferols / therapeutic use*
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Female
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Fibroblast Growth Factor-23
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Fibroblast Growth Factors / metabolism*
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Humans
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Hypercalcemia
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Hyperparathyroidism, Secondary / complications
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Hyperparathyroidism, Secondary / drug therapy*
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Hyperparathyroidism, Secondary / etiology
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Hyperphosphatemia
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Kidney Failure, Chronic / complications
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Longitudinal Studies
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Male
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Osteogenesis / drug effects*
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Parathyroid Hormone / blood*
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Polyamines / administration & dosage
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Polyamines / therapeutic use
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Sevelamer
Substances
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Bone Density Conservation Agents
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Ergocalciferols
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FGF23 protein, human
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Parathyroid Hormone
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Polyamines
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1 alpha-hydroxyergocalciferol
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Fibroblast Growth Factors
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Fibroblast Growth Factor-23
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Sevelamer
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Calcitriol
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Calcium Carbonate