Calcium kinetics in children with osteogenesis imperfecta type III and IV: pre- and post-growth hormone therapy.
Children with osteogenesis imperfecta (OI) type III and type IV were studied using a (42)Ca stable isotope technique. Serum dilution kinetics of (42)Ca were studied pre- and post-growth hormone (GH) treatment in 9 OI III (age range 5-9 years) and 8 OI IV patients (age range 5-12 years). Each subject was studied twice: at baseline and following GH therapy (range 1-1.5 years). Isotopic enrichments of (42)Ca were followed over 7 days using thermal ionization mass spectrometry. A binding site model, which describes reversible and irreversible binding of calcium (Ca) ions to postulated short- and long-term binding sites in bone, was used to analyze the kinetic data. In type III patients, GH treatment (1) increased the fraction of short-term binding sites, theta (0.777 +/- 0.112 versus 0.877 +/- 0.05, respectively; P = 0.034); (2) increased the apparent half-life of a Ca ion attached to the long-term binding site by 76% (P = 0. 009); (3) although not statistically significant (P = 0.098), a trend toward an increased growth rate was observed with increasing change in theta (Deltatheta); (4) patients experienced a 75% increase in growth rate during the first 6 months of treatment. In type IV patients, GH treatment increased the apparent half-life of a Ca ion attached to the long-term binding site by 83% (P = 0.048), however, no trend toward an increased growth rate was observed with increasing Deltatheta in these patients. These significant changes in Ca binding to bone may influence growth in type III patients.
Vieira
N E
NE
National Institute of Child Health and Human Development, National Institutes of Health, Laboratory of Cellular and Molecular Biophysics, Bethesda, MD 20892, USA.
Goans
R E
RE
Weiss
G H
GH
Hopkins
E
E
Marini
J C
JC
Yergey
A L
AL
D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002127:Calcium Isotopes; D002648:Child; D002675:Child, Preschool; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007201:Indicator Dilution Techniques; D013058:Mass Spectrometry; D010013:Osteogenesis Imperfecta / Q000188:drug therapy / Q000378:metabolism*
D002127:Calcium Isotopes; D019382:Human Growth Hormone; D002118:Calcium