Correlative Raman spectroscopy and electron microscopy identifies glycogen rich deposits correlated with local structural defects in long bones of type IV osteogenesis imperfecta patients

Osteogenesis imperfecta (OI) is a genetic bone disease occurring in approximately 1 in 10,000 births, usually as a result of genetic mutation. OI patients suffer from increased fracture risk and – depending on the severity of the disease – deformation of the limbs, which can even lead to perinatal death.

Despite extensive studies, the way in which the genetic mutation is translated into structural and compositional anomalies of the tissue is still an open question. Different observations have been reported, ranging from no structural (or chemical) differences to completely chaotic bone structure and composition.

Here, we investigated bone samples from two adolescent OI-IV patients, focusing on the bone structure and chemistry in naturally occurring fractures. The exposed fracture plane allows the investigation of the structure and composition of the weakest bone plane. We do so by combining scanning electron microscopy (SEM) imaging with chemical information from Raman microscopy.

The exposed fracture planes show different regions within the same tissue, displaying normal osteonal structures next to disorganized osteons and totally disordered structures, while the collagen mineralization in all cases is similar to that of a healthy bone.

In addition, we also detected significant amounts of depositions of glycogen-rich, organic, globules of 250–1000 nm in size. These depositions point to a role of cellular disfunction in the disorganization of the collagen in qualitative OI.

Overall, our results unite multiple, sometimes contradicting views from the literature on qualitative OI.