Osteogenesis imperfecta (OI) is a hereditary disease with a generalized involvement of the connective tissue caused by collagen type 1 mutations. The clinical appearance is broad with fractures as the key symptom. Only few genotypephenotype correlations have been established. We aim to characterize the Danish OI population thoroughly including DXA and HRpQCT, anthropometry, patient history, and genetic background.
This cross-sectional study includes 85 Danish adult OI patients, aged 1972 (mean 44.9±15.5 years; 38 men, 47 women). All patients are classified according to the Sillence classification: 58 type I, 12 type III and 15 type IV. In a subset of patients collagen sequencing (n=53) and structural collagen analyses (n=60) were performed. We found OI causing mutations in 44 patients (27 in COL1A1, 17 in Col1A2), however, no obvious mutations was found in nine patients. A quantitative collagen defect was found in 35 patients, and a qualitative defect in 25 patients.
The most severely affected patients (type III) had the highest fracture rate; 1.16 (0.433.96) fractures/year compared to 0.27 (02.26) and 0.32 (00.55) fractures/year in patients with type I and type IV, respectively, P=0.001. Lumbar aBMD correlates with fracture rate, R2=0.126, p=0.003. This is not the case for hip aBMD, forearm vBMD(HRpQCT) and tibial vBMD(HRpQCT). The patients with a qualitative collagen defect had lower lumbar aBMD, P=0.004 and a higher fracture rate, P=0.002 than patients with a quantitative collagen defect. They also had reduced height (147±25 vs 161±10 cm, P=0.02), sitting height (72±12 vs 81±8 cm, P=0.003) and armspan (151±24 vs 169±13 m, P=0.002).
We found poor correlation between OI disease severity and aBMD and vBMD. Since the most severe cases of OI have qualitative collagen defects, we suggest extending routine patient evaluation with mutation screening and collagen structural analyses. Our data suggest that a classification of autosomal dominant OI based on biochemical and genetic findings may be developed.
17 - 20 May 2014
European Calcified Tissue Society