Mechanical characterization of Col1a1 +/- osteogenesis imperfecta bone revealed altered mechanical stiffness heterogeneity across scales.

This study presents a novel integrated multiscale approach that combines whole-bone strain mapping, nanoscale mechanical testing, and compositional profiling to reveal how structural changes across scales impair bone quality in osteogenesis imperfecta (OI). OI is a genetic disorder caused by mutations in type I collagen that leads to fragile bones. Using femurs from male Col1a1+/- haploinsufficient OI (type I) mice, we examined how mechanics relate to structural and compositional changes. The results indicate that OI bone exhibits increased heterogeneity in mechanical properties and lacks the characteristic alternating soft and stiff lamellae that are critical for absorbing fracture energy in healthy bone. While previous studies have investigated OI biomechanics, few have integrated framework spanning organ-, tissue-, and nanoscale levels. Our results underscore the importance of restoring the hierarchical bone architecture and suggest a need for therapies that target bone quality, not just bone mass, to effectively mitigate fracture risk in OI.