Osteogenesis imperfecta (OI) is a hereditary disease characterised by compromised connective tissue predominantly caused by mutations in the two collagen type I (COL-1) encoding genes, COL1A1 and COL1A2. Symptoms, as fractures, bone deformity, hearing loss and blue sclera, reflect the ubiquity of COL-1 throughout the body. The study aim was to improve our understanding of the link between the molecular background and clinical manifestations by investigating the genotype, COL-1 structure, patient history, anthropometry and skeletal phenotype including DXA and HRpQCT in a large adult OI population. The study comprised 85 adult OI patients (Sillence: 58 OI type I, 12 OI type III, and 15 OI type IV). All patients underwent DXA, HRpQCT, biochemical screening and anthropometry. Medical history was collected. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified in 66 families (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure by SDS-PAGE was performed in a subset (n=67). The mutations located at the C-terminal end of both genes, were more severe and the mutations in COL1A2 generally caused more severe OI. The patients with a qualitative collagen defect had lower lumbar spine aBMD (p=0.004) and more fractures (p=0.002) than patients with a quantitative COL-1 defect. They also had reduced height, 147±25 cm vs. 161±10 cm (p=0.02), sitting height, 72±12 cm vs. 81±8 cm (p=0.003), and armspan, 151±24 cm vs. 169±13m (p=0.002, T-test). HRpQCT revealed significant differences between patients with OI type I and IV with more decreased vBMD (p<0.005), decreased cortical thickness (p<0.001) and reduced trabecular number (p<0.005) in the mildly affected OI type I patients compared with OI type IV. Since the most severe cases of OI have qualitative COL-1 defects, we suggest that extension of the routine patient evaluation with mutation screening and structural collagen analysis may provide valuable information in the long-term management of adult OI patients.
Disclosure: The authors declared no competing interests.