Multiscale Structure and Mechanics of Bone in Glucocorticoid Induced Osteoporosis

Authors: Li Xi (Queen Mary, University of London)
Co-authored by industrial partner: No

Type: Thesis

State: Published (Approved)
Published: September 2016

Abstract: Glucocorticoid induced osteoporosis (GIOP), is the most common form of secondary osteoporosis, lowering bone mechanical properties. Glucocorticoids have effects on bone cells and bone remodelling cycles, resulting in alterations in bone structure and quality which increases fracture risk. However, the mechanisms by which GIOP increases fracture risk are not clearly understood, and clinical tools like dual-energy X-ray absorptiometry (DEXA) underestimate fracture risk. Therefore, it is likely that significant (but unknown) alterations in bone material quality at the nano- and microscale play an important role in increased fracture risk. Here, a mouse model for Cushing’s disease (endogenous production of glucocorticoids) was used, together with in situ mechanical testing combined with synchrotron X-ray scattering/diffraction (SAXS/WAXD), to investigate these nanoscale deformation alterations. Nanoscale deformation models were developed and used to predict fibrillar modulus from bone mineral concentration, and to simulate the strain rate effects on fibrillar and mineral modulus of bone. Our modelling results showed good agreement with experimental results. The microscale structure, composition and mechanical properties of femoral cortex in Crh−120/+ and wild-type mice at different developmental ages were studied using synchrotron diffraction, scanning electron microscopy, X-ray microtomography and nanoindentation. We find that the nanoscale fibrillar and mineral deformation mechanisms, microscale mineralization distribution and local tissue modulus of bone were significantly changed in Crh−120/+ mice compared to their wild-type littermates. Increased deformability of fibrils and mineral platelets were accompanied with more disorganized arrangement of both phases, as compared with wild-type mice. At the microscale, reduced mineral content with a heterogeneous mineralization and reduced local tissue modulus near femoral endosteal cortex were observed in Crh−120/+ mice. We propose that these alterations in nanoscale deformation mechanisms, and microscale heterogeneities are critical for the enhanced macroscale bone fragility in GIOP.

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I22-Small angle scattering & Diffraction