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.
National Institute of Child Health and Human Development, National Institutes of Health, Laboratory of Cellular and Molecular Biophysics, Bethesda, MD 20892, USA.
N E
NE
Vieira
R E
RE
Goans
G H
GH
Weiss
E
E
Hopkins
J C
JC
Marini
A L
AL
Yergey
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