ESPE Abstracts

Background: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder with variable phenotype, mainly characterized by bone fragility, short stature and non-skeleton findings. Since growth failure is a predominant feature of OI, recombinant human growth hormone (rhGH) has been suggested as a potential intervention. We describe two boys with OI type I treated with rhGH.

Case Reports: Patient 1 had the first fracture at 1.2 years, and 3 other fractures before starting bisphosphonate at 2.8 years. He has gray sclera, slightly valgus knees, mild spinal deformity and excavated thorax. Height Z-score (H-SDS) before bisphosphonate was -0.49 and target H-SDS was -0.76 (mother with OI). At 8-years-old the bone age (BA) was compatible with chronological age (CA) and endocrine workup showed: growth hormone (GH) peak of 9.03ng/mL after clonidine stimulation and normal IGF-1 concentration. Therapy with rhGH started (0.043mg/kg/day) when his H-SDS was -1.66. Puberty started at age 12, when H-SDS was -0.20. At the last visit he was 14,2-years-old, H-SDS was +0.04, at Tanner stage 4 and BA was compatible with CA. Bone mineral density (BMD) Z-score was +2.3 (total body less head, TBLH) and +0.3 (lumbar spine, LS), evaluated by DXA. Patient 2 had his first fracture at 8 months, and 4 other fractures before bisphosphonate at 6.1 years. He has blue sclera, excavated thorax, scoliosis, and mild limb deformities. H-SDS before bisphosphonate was -3.74, and target H-SDS was -1.72 (father with OI). At 10.1-years-old H-SDS was -2.83, BA was 7-years-old, and endocrine workup showed: GH peak of 10,1ng/mL after clonidine stimulation and low-normal IGF-1. rhGH treatment started (0.051mg/kg/day) at 10.1-years-old. Puberty started at 11-years-old, and at the last visit he was 13.7-years-old, H-SDS was -1.78, at Tanner stage 3, BA was 13-years-old, and the BMD Z-score was -0.8 (TBLH) and +0.2 (LS).

Conclusion: rhGH has been proposed as an intervention for mild forms of OI to improve growth rate, with conflicting results on fracture rate and BMD. Some studies have suggested positive effects of rHGH on height, however its use is not universally accepted. We present two cases of boys treated with rhGH, with positive results on growth and no negative influence on fracture rate.