Bone turnover and 1,25-dihydroxycholecalciferol during treatment with phosphate binders.
The effect of dietary phosphate restriction with high-dose aluminum hydroxide or calcium carbonate on bone disease assessed by histomorphometry and on the plasma levels of 1,25-dihydroxycholecalciferol was investigated in 12 children with chronic renal failure (GFR 8 to 45 ml/min/1.73 m2, age 5 to 15 years) over a one year period. Prior to treatment patients had biochemical and histological hyperparathyroidism with greatly increased bone formation rates. During treatment, plasma phosphate levels decreased from the upper to the lower limit of normal for age (pre, 1.69 +/- 0.06 mmol/liter; 6 months, 1.28 +/- 0.06 mmol/liter; 1 year, 1.34 +/- 0.06 mmol/liter; P less than 0.01). Circulating 1,25-dihydroxycholecalciferol rose to supranormal levels within three months and remained high throughout the period of study (pre, 96 +/- 32 pmol/liter; 6 months, 144 +/- 46 pmol/liter; 1 year, 169 +/- 53 pmol/liter; P less than 0.001). Significant falls in bone formation rate at tissue and cellular levels (P less than 0.005) and in total resorption surface (P less than 0.005) were observed. A mild mineralization defect present before treatment worsened, with a decrease in mineral appositional rate (P less than 0.01) and increase in mineralization lag time (P less than 0.01). Staining for aluminum in post-treatment biopsies was positive in 9 of 11 cases. Phosphate restriction produced suppression of biochemical and histological hyperparathyroidism and sustained elevation of circulating 1,25-dihydroxycholecalciferol. The adverse changes in bone mineralization may be related to aluminum hydroxide therapy; calcium carbonate is therefore recommended.
Turner
C
C
Evelina Children's Hospital, London, United Kingdom.
Compston
J
J
Mak
R H
RH
Vedi
S
S
Mellish
R W
RW
Haycock
G B
GB
Chantler
C
C
D000293:Adolescent; D000536:Aluminum Hydroxide / Q000627:therapeutic use; D001862:Bone Resorption / Q000187:drug effects; D002117:Calcitriol / Q000097:blood*; D002119:Calcium Carbonate / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D010012:Osteogenesis / Q000187:drug effects; D010710:Phosphates / Q000097:blood*
D010710:Phosphates; D000536:Aluminum Hydroxide; D002117:Calcitriol; D002119:Calcium Carbonate