GROWTH-HORMONE TREATMENT IN OSTEOGENESIS IMPERFECTA WITH QUANTITATIVEDEFECT OF TYPE-I COLLAGEN-SYNTHESIS

Objectives: We studied growth rate, bone density, and bone metabolism in patients affected by type I osteogenesis imperfecta (OI) with quant itative defect in type I collagen synthesis during treatment with huma n growth hormone (hGH), being aware of its collagen-stimulating synthe sis activity in vitro. Study design: Fourteen patients (6 boys; ages 4 .8 to 10.8 years) were studied. Any structural alteration in the colla gen chains was excluded, and reduced production of structurally normal type I collagen (increase in type III/type I collagen; reduction in t he messenger ribonucleic acid alpha 1 (I)/alpha 2(I) ratio) was demons trated. The patients were divided into two groups comparable in sex, a ge, height, and clinical severity of OI; seven patients (three boys) w ere 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 mon ths, and bone age was determined at the start, after 1 year of treatme nt, and 1 year after its completion. Every 3 months, serum insulin-lik e growth factor type I, osteocalcin, carboxyterminal propeptide of typ e I procollagen, alkaline phosphatase, calcium, and phosphorus levels and urinary hydroxyproline and calcium levels were determined. Bone ma ss measurements were carried out at the start of the study in all pati ents and repeated after 12 months in treated patients at the lumbar sp ine by dual-energy x-ray absorptiometry and by anteroposterior (second , third, and fourth lumbar vertebrae) and lateral (third lumbar verteb ra) 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 significa ntly in comparison with the pretreatment period (from 3.57+/-0.55 to 6 .01+/-0.69 cm/yr; p <0.05) and with the untreated group (p <0.05). Bon e age did not advance faster than chronologic age. The fracture index per year was low before treatment, and during therapy no patient had a ny fractures. Serum osteocalcin levels were statistically lower than i n control subjects before treatment and increased significantly after 12 months (3.3+/-1.0 vs 2.1+/-0.9 nmol/L; p <0.05). Serum levels of ca rboxyterminal propeptide of type I procollagen were significantly lowe r than normal values before treatment (164.6+/-46.7 vs 310.3+/-97.6 ng /ml; p <0.05) and rose, but not significantly, during and after treatm ent. Before therapy, patients with OI had significantly lower lumbar a nteroposterior, lateral, and calculated true bone density than the nor mal population of the same sex compared for both age and height. After hGH treatment, bone density increased significantly in the lumbar spi ne, in anteroposterior and lateral scans (+2.6%+/-2.5% and +9.8%+/-14. 0%, respectively; p <0.05), and in calculated true bone density (+11.4 %+/-6.7%; p <0.05). Conclusions: From our results, we conclude that hG H treatment in moderate OI does not increase the fracture risk in trea ted patients in the short term, significantly increases the rate of li near growth velocity, and increases bone turnover and mineral content in trabecular bone at the lumbar spine.