Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis

• Published in: The Journal of pediatrics 1996-09, Vol.129 (3), p.432-439
• Main Authors: Antoniazzi, Franco, Bertoldo, Francesco, Mottes, Monica, Valli, Maurizia, Sirpresi, Stefania, Zamboni, Giorgio, Valentini, Roberta, Tatò, Luciano
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Biological and medical sciences; Bone Density; Calcium - metabolism; Child; Child, Preschool; Collagen - biosynthesis; Female; Growth; Growth Hormone - therapeutic use; Hormones. Endocrine system; Humans; Hydroxyproline - urine; Insulin-Like Growth Factor I - analysis; Male; Medical sciences; Osteocalcin - blood; Osteogenesis Imperfecta - metabolism; Osteogenesis Imperfecta - physiopathology; Osteogenesis Imperfecta - therapy; Peptide Fragments - blood; Pharmacology. Drug treatments; Procollagen - blood
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(96)70077-X

OBJECTIVES: We studied growth rate, bone density, and bone metabolism in patients affected by type I osteogenesis imperfecta (OI) with quantitative defect in type I collagen synthesis during treatment with human growth hormone (hGH), being aware of its collagen-stimulating synthesis activity in vitro. STUDY DESIGN: Fourteen patients (6 boys; ages 4.8 to 10.8 years) were studied. Any structural alteration in the collagen chains was excluded, and reduced production of structurally normal type I collagen (increase in type III/type I collagen; reduction in the messenger ribonucleic acid α1[I]/α2[I] ratio) was demonstrated. The patients were divided into two groups comparable in sex, age, height, and clinical severity of OI; seven patients (three boys) were treated for 12 months with hGH at a dosage of 0.2 mg/kg per week (0.6 IU/kg per week), in six injections subcutaneously, and seven were followed as control subjects. Auxologic data were measured every 3 months, and bone age was determined at the start, after 1 year of treatment, and 1 year after its completion. Every 3 months, serum insulin-like growth factor type I, osteocalcin, carboxyterminal propeptide of type I procollagen, alkaline phosphatase, calcium, and phosphorus levels and urinary hydroxyproline and calcium levels were determined. Bone mass measurements were carried out at the start of the study in all patients and repeated after 12 months in treated patients at the lumbar spine by dual-energy x-ray absorptiometry and by anteroposterior (second, third, and fourth lumbar vertebrae) and lateral (third lumbar vertebra) scan. Results were expressed as areal (anteroposterior and lateral) bone density (in milligrams per square centimeter) and as calculated true density (in milligrams per cubic centimeter). RESULTS: After 12 months, linear growth velocity in treated patients increased significantly in comparison with the pretreatment period (from 3.57 ± 0.55 to 6.04 ± 0.69 cm/yr; p