Modifications to Nano- and Microstructural Quality and the Effects on Mechanical Integrity in Paget's Disease of Bone

Abstract

Paget's disease of bone (PDB) is the second most common bone disease mostly developing after 50 years of age at one or more localized skeletal sites; it is associated with severely high bone turnover, bone enlargement, bowing/deformity, cracking, and pain. Here, to specifically address the origins of the deteriorated mechanical integrity, we use a cohort of control and PDB human biopsies to investigate multiscale architectural and compositional modifications to the bone structure (ie, bone quality) and relate these changes to mechanical property measurements to provide further insight into the clinical manifestations (ie, deformities and bowing) and fracture risk caused by PDB. Here, at the level of the collagen and mineral (ie, nanometer-length scale), we find a 19% lower mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for the 14% lower stiffness and 19% lower hardness promoting plastic deformation in pathological bone. At the microstructural scale, trabecular regions are known to become densified, whereas cortical bone loses its characteristic parallel-aligned osteonal pattern, which is replaced with a mosaic of lamellar and woven bone. Although we find this loss of anisotropic alignment produces a straighter crack path in mechanically-loaded PDB cases, cortical fracture toughness appears to be maintained due to increased plastic deformation. Clearly, the altered quality of the bone structure in PDB affects the mechanical integrity leading to complications such as bowing, deformities, and stable cracks called fissure fractures associated with this disease. Although the lower mineralization and loss of aligned Haversian structures do produce a lower modulus tissue, which is susceptible to deformities, our results indicate that the higher levels of plasticity may compensate for the lost microstructural features and maintain the resistance to crack growth.

The fracture mechanics of human bone: influence of disease and treatment

“…75 Interestingly, fracture toughness measurements on healthy and diseased tissue from the iliac crest show little difference in toughness ( Figure 9a); however, the mechanism for resisting crack propagation changes. 37 Despite the limited number of toughness samples restricting statistical comparisons, there was still clear evidence of higher fracture toughness in the transversely oriented control and PDB bone samples, in comparison with the longitudinally oriented bone, which has a comparatively weak resistance to crack growth. 27 Indeed, the healthy (control) bone resists crack propagation and derives toughness in the usual way through crack deflection mechanisms (Figure 9b).…”

“…Currently, fracture risk is mainly measured through dual-energy X-ray absorptiometry (DXA), where the degree of X-rays absorbed by the bone mineral provides a prediction of fracture risk. As the degree of bone mineralization shows a rather narrow range in health and disease, 37,41 standard DXA diagnostics provide a helpful measure of areal bone mineral density, which is based on the present porosity and volume fraction of the bone (that is, bone quantity). In addition, DXA provides valuable information due to its widespread global availability and the existence of large reference populations; however, it is not necessarily an optimal indicator for predicting fracture risk.…”

“…Thus, the compositional changes in the diseased tissue resulting in a lower mineralization affect both the elastic (that is, stretching of bonds generating stiffness) and the plastic (that is, permanent deformation promoting ductility and energy The fracture mechanics of human bone EA Zimmermann et al absorption) mechanical properties, resulting in a lower stiffness and more plasticity. 37 Paget's disease also affects the higher level structural organization in bone. In cortical regions, instead of the structural patterns characteristic of healthy tissue (that is, parallel aligned Haversian canals), the pathological tissue is a patchwork of lamellar and woven bone, with less organized collagen fiber orientation.…”

“…Although the ability for the diseased tissue to generate extrinsic toughening is severely degraded, the bone structure compensates through a more pronounced mechanical resistance through plastic deformation, that is, Paget's diseased bone shows higher ductility (intrinsic toughness). 37 Indeed, the Paget's tissue has a lower mineralization and a correspondingly lower hardness, which both indicate that the tissue has the capacity for higher levels of plasticity similar to other tissues with low mineralization levels and significant plastic deformation. 76,77 Thus, although toughness is generated through crack deflection in healthy bone (extrinsic toughening), the diseased tissue may generate toughness primarily through intrinsic plasticity mechanisms that absorb energy during deformation and fracture.…”

“…20 The effects of porosity can be corrected by normalizing the applied stress by the bone volume fracture, which is especially critical when comparing the mechanical properties of groups with significantly different porosities. 19,37 Thus, although bone porosity is not the sole determinant of fracture risk in bone, it should be considered when addressing the mechanical properties of cortical bone.…”