Connective Tissue Research, vol.63, no.4, pp.349-358, 2022 (SCI-Expanded)
Background: Osteogenesis imperfecta (OI), is a heritable, heterogeneous connective tissue disorder, characterized by fragile bones. There are conflicting results about genotype-phenotype correlations and efficiency of bisphosphonate treatment in this disorder. Aim: We aimed to evaluate the clinical, genetic characteristics, and long-term follow-up results of children and adolescents with OI. Materials and methods: A two-center retrospective study was conducted using demographic, clinical, and genetic data obtained from the medical records of the patients. Results: Twenty-nine patients (62% male, median age; 3.6 years) with OI diagnosis from 26 families were included in the study. Thirteen different variants (nine were novel) were described in 16 patients in COL1A1, COL1A2, and P3H1 genes. Our siblings with homozygous P3H1 variants had a severe phenotype with intrauterine and neonatal fractures. Twenty-two patients were treated with bisphosphonates (17 of them with pamidronate, five with alendronate) with a median duration of 3.0 (1.6–4.8) years. Eleven patients (50%) suffered from fractures after the treatment. Haploinsufficiency variants in COL1A1 caused a milder skeletal phenotype with less fracture count and better treatment outcomes than structural variants. When compared with the anthropometric measurements at the initial diagnosis time, height Z-scores were lower on the last clinical follow-up (p = 0.009). Conclusions: We could not find an obvious genotype-phenotype correlation in Turkish OI patients with COL1A1 or COL1A2 variants. Treatment with pamidronate was effective in reducing fracture counts, without any long-term adverse effects.