Calcium Kinetics in Children with Osteogenesis Imperfecta Type III and IV: Pre- and Post-Growth Hormone Therapy

Abstract

Children with osteogenesis imperfecta (OI) type III and type IV were studied using a ⁴²Ca stable isotope technique. Serum dilution kinetics of ⁴²Ca 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 ⁴²Ca 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, θ (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 θ (Δθ); (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 Δθ in these patients. These significant changes in Ca binding to bone may influence growth in type III patients.