Longitudinal change of bone microarchitecture and fracture risk in adults with osteogenesis imperfecta.

PURPOSE: Incident fractures remain the major complications in adults with osteogenesis imperfecta (OI). Cross-sectional studies have shown impaired bone microarchitecture (BM), but the longitudinal changes and their contribution to fracture risk remain unknown. Here, we investigated the changes in BM and their associations with clinical, genetic factors and incident fractures. METHODS: Fifty-five adults with OI (23 men, 32 women, including 6 postmenopausal; mean age 43 ± 14 years) were followed for a median of 2.7 years (IQR 2.1-4). HR-pQCT was used to measure the cortical (Ct) bone mineral density (vBMD) and thickness and the trabecular (Tb) bone volume (BV/TV), vBMD at the distal radius and tibia. Longitudinal changes adjusted for clinical parameters were analysed with mixed-effects models. We investigated the associations of BM changes and the incident fractures by logistic regression adjusted for age, sex/menopause, genotype and treatment. RESULTS: At the distal radius, Tb.vBMD, Tb.BV/TV and Ct.Pm and were low in premenopausal and postmenopausal women at baseline. Tb.BV/TV declined in men (-0.0030/yr, p < 0.01) and premenopausal women (-0.0027/yr, p < 0.05). Ct.Th decreased also in men (-0.0735 mm/yr) and premenopausal women (-0.0813 mm/yr, p < 0.001). However, Tb.BV/TV increased (+0.0019/yr, p < 0.05) and Ct.Th decreased (-0.0819 mm/yr, p < 0.0001) in postmenopausal women, suggesting trabecularization of cortical bone. Incident fractures during follow-up was similar in the genetic variants (p = 0.179). Neither Tb.BV/TV, Ct.Th nor vBMD changes predicted incident fractures. CONCLUSION: Bone microarchitecture deteriorates over time in adults with OI and more after menopause. However, longitudinal changes do not predict incident fractures, highlighting the complex determinants of fracture risk in OI.