The changes in bone's nanostructure associated with bone fragility & bisphosphonate treatment

Abstract

The contribution of the nanostructure to whole bone strength has long been debated. However the impact of the collagen-mineral matrix on whole bone mechanics has yet to be tested. At the start of the study, bone volume and microarchitecture were found to not entirely account for bone strength, even though new ITS techniques were included, and thus it seemed possible that the gap could be attributed to the nanostructure.

State-of-the-art synchrotron imaging was used to compare nanomechanics between bones from ageing non-fracture donors and ageing fracture patients, half of whom had been prescribed bisphosphonate. Fracture patients exhibited with lower tissue, collagen and mineral strains than non-fracture patients, suggesting that their nanostructures were less deformable. In addition, the fracture patients exhibited with wider mineral crystals, providing for larger surface areas for interfacial bonding with collagen fibrils, and thus preventing the unwinding and sliding of the matrix during loading. The less deformable matrix may reduce macroscopic strength via a cascade effect by easier initiation and growth of microcracks in the collagen-mineral matrix and limiting the bone’s ability to bend and absorb energy during a trip or fall.

This new knowledge of the importance of the nanoscale deformation to whole bone strength could fill gaps in current diagnostics and treatments, if it were possible to measure deformation properties in vivo. Nanoindentation was developed to measure such deformations, and as such, a benchtop system was used to measure material properties of the three groups, and the data was correlated with nanostrain data. However, nanoindentation material properties and fibril and mineral strains were not correlated. In addition to the lack of correlation to microstructure and macro level strength and stiffness, it seems that nanoindentation does not measure material properties accurately and thus other alternatives need to be looked into for in-vivo measurements at the nanoscale.