title: Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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 < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD (p < 0.005), thinner cortexes (p < 0.001), and reduced trabecular number (p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA.
  
  
  
  The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage Hansensgade 2, Aarhus C, Denmark. janniehald@gmail.com.
authors.forename: J D
authors.initials: JD
authors.lastname: Hald
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Department of Endocrinology, Hospital of Southwest Denmark, Esbjerg, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Folkestad
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage Hansensgade 2, Aarhus C, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Harsløf
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Lund
authors.affiliation: Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Duno
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Jensen
authors.affiliation: Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Neghabat
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Brixen
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage Hansensgade 2, Aarhus C, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Langdahl
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain
keywords: Collagen type 1; DXA; Genotype; HRpQCT; Osteogenesis imperfecta