Cortical bone material / compositional changes in children with mild osteogenesis imperfecta

Abstract

Osteogenesis imperfecta (OI) is a heritable connective-tissue disorder characterized by skeletal fragility (amongst other manifestations) despite relatively preserved bone mineral density (BMD), suggesting that alterations in bone quality play a central role. Intrinsic matrix defects, including disrupted collagen assembly, altered enzymatic cross-linking, changes in matrix hydration, and disturbed mineral chemistry, are consistently observed and contribute to impaired mechanical competence. Although Raman spectroscopy is well suited to probe these compositional features, its application in OI has been limited to date, and prior studies have seldomly accounted for tissue age, a critical determinant of local bone composition. Whether cortical bone exhibits tissue-age–dependent spectroscopic abnormalities similar to those reported in trabecular bone remains unknown. To address this gap, in the present study we used Raman microspectroscopy to analyze the cortical compartment of iliac bone biopsies from 16 children with mild OI (aged 2–15 years). Bone-forming endosteal and osteonal surfaces were analyzed across three specifically defined tissue ages to characterize mineral and matrix composition. Compared with age-matched healthy controls, OI cortical tissue exhibited elevated mineral/matrix ratio, nanoporosity, and pyridinoline cross-link content, coupled with decreased crystallinity mineral crystallites. These findings reveal distinct cortical matrix abnormalities in children with mild OI mutations and complement previously published data obtained in the cancellous compartment. The altered compositional profile and accelerated maturation kinetics likely contribute to compromised tissue-level mechanical competence and increased fracture susceptibility in children diagnosed with mild OI.