Skeletal phenotypes in adult patients with osteogenesis imperfecta—correlations with COL1A1/COL1A2 genotype and collagen structure

Summary Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. Introduction OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. Methods The study comprised 85 OI patients aged 45 (19–78) years, Sillence type I ( n = 58), III ( n = 12), and IV ( n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1 , 22 in COL1A2 ). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset ( n = 67). Results A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect ( p