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Growth hormone treatment in osteogenesis imperfecta with quantitative defect of type I collagen synthesis
F Antoniazzi1, F Bertoldo, M Mottes
1Clinica Pediatrica, Universitá di Verona, Italy.
Insights
Human growth hormone (hGH) treatment significantly increased linear growth velocity and bone mineral content in patients with osteogenesis imperfecta (OI). This hGH therapy did not elevate fracture risk in the short term for OI patients.
Area of Science:
- Pediatric Endocrinology
- Skeletal Dysplasias
- Metabolic Bone Disease
Background:
- Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragile bones due to defects in type I collagen synthesis.
- Quantitative defects in type I collagen synthesis lead to reduced bone mass and increased fracture risk.
- Human growth hormone (hGH) has demonstrated in vitro collagen-stimulating activity, suggesting potential therapeutic benefits for OI.
Purpose of the Study:
- To evaluate the efficacy of human growth hormone (hGH) treatment on growth rate, bone density, and bone metabolism in patients with type I osteogenesis imperfecta (OI).
- To assess the safety of hGH treatment concerning fracture risk in OI patients.
- To investigate the impact of hGH on bone turnover markers and collagen synthesis in OI.
Main Methods:
- A randomized controlled trial involving 14 pediatric patients with type I OI, divided into hGH-treated (n=7) and control (n=7) groups.
- hGH was administered subcutaneously at 0.2 mg/kg/week for 12 months.
- Measurements included auxologic data, bone age, serum markers (IGF-I, osteocalcin, P1NP, ALP, Ca, P), and urinary hydroxyproline.
- Lumbar spine bone mineral density was assessed using dual-energy x-ray absorptiometry (DXA) before and after treatment.
Main Results:
- hGH treatment significantly increased linear growth velocity (from 3.57 to 6.04 cm/yr) compared to baseline and the control group (p < 0.05).
- No increase in fracture index was observed during hGH therapy; bone age did not advance faster than chronological age.
- Significant increases in serum osteocalcin levels and lumbar spine bone density (anteroposterior and lateral scans) were noted after hGH treatment (p < 0.05).
Conclusions:
- hGH treatment is effective in increasing linear growth velocity in children with moderate type I OI.
- hGH therapy appears safe in the short term, with no increased fracture risk observed.
- hGH treatment positively influences bone turnover and increases bone mineral content in the lumbar spine of OI patients.
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 alpha 1 (I)/ alpha 2 (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 < 0.05) and with the untreated group (p < 0.05). Bone age did not advance faster than chronologic age. The fracture index per year was low before treatment, and during therapy no patient had any fractures. Serum osteocalcin levels were statistically lower than in 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 carboxyterminal propeptide of type I procollagen were significantly lower 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 treatment. Before therapy, patients with OI had significantly lower lumbar anteroposterior, lateral, and calculated true bone density than the normal population of the same sex compared for both age and height. After hGH treatment, bone density increased significantly in the lumbar spine, in anteroposterior and lateral scans (+2.6 +/- 2.5% and +9.8% +/- 14.0%, respectively; p < 0.05).
Conclusions:
From our results, we conclude that hGH treatment in moderate OI does not increase the fracture risk in treated patients in the short term, significantly increases the rate of linear growth velocity, and increases bone turnover and mineral content in trabecular bone at the lumber spine.