Genetics and Bone Mineral Density Predict the Fractures in Adults With Osteogenesis Imperfecta: A Prospective Study

Context: Osteogenesis imperfecta (OI) is a rare genetic bone disorder characterized by recurrent fractures. In adults, the value of bone mineral density (BMD) in fracture risk is unknown. Objective: We prospectively investigated changes in BMD over time and analyzed the determinants of fracture in OI. Methods: Among 106 individuals with grade 1 and 4 OI in the Reference Centre of Rare Bone Diseases in Paris, we included those with BMD measurements at 1 or more skeletal sites (hip, lumbar spine, radius) from 2000 to 2022. Results: For 71 individuals with reliable measurements (44 women, 8 postmenopausal; mean age 41.4 +/- 13.7 years), baseline BMD was low at the lumbar spine only (mean Z-score -2.3 +/- 1.5), affecting mainly men (mean Z-score -3 +/- 1.6). Longitudinal changes were assessed for a median follow-up of 5.1 years (interquartile range 3.2-8.8). On adjustment for age, sex, and body mass index, BMD did not significantly change at any site. Logistic regression analysis revealed a high probability of fracture with baseline BMD Z-score <-2 SD vs >=-2 SD [odds ratio 4.38, 95% confidence interval (CI) 1.10-21.75, P = .048] and harboring splicing, stop codon, and frameshift variants of COL1 gene (odds ratio 29.8, 95% CI 2.56-1503, P = .024). Conclusion: Our OI cohort showed low BMD at the lumbar spine but no significant change at any site after a median of 5.0 years of follow-up. The probability of fracture was associated with baseline BMD Z-score <-2 SD vs >=-2 SD and harboring COL1 splicing, stop codon, and frameshift variants.