Assessment of the effect of reduced compositional heterogeneity on fracture resistance of human cortical bone using finite element modeling

Abstract

The recent reports of atypical femoral fracture (AFF) and its possible association with prolonged bisphosphonate (BP) use highlighted the importance of a thorough understanding of mechanical modifications in bone due to bisphosphonate treatment. The reduced compositional heterogeneity is one of the modifications in bone due to extensive suppression of bone turnover. Although experimental evaluations suggested that compositional changes lead to a reduction in the heterogeneity of elastic properties, there is limited information on the extent of influence of reduced heterogeneity on fracture resistance of cortical bone. As a result, the goal of the current study is to evaluate the influence of varying the number of unique elastic and fracture properties for osteons, interstitial bone, and cement lines on fracture resistance across seven different human cortical bone specimens using finite element modeling. Fracture resistance of seven human cortical bone samples under homogeneous and three different heterogeneous material levels was evaluated using a compact tension test setup. The simulation results predicted that the crack volume was the highest for the models with homogeneous material properties. Increasing heterogeneity resulted in a lower amount of crack volume indicating an increase in fracture resistance of cortical bone. This reduction was observed up to a certain level of heterogeneity after which further beneficial effects of heterogeneity diminished suggesting a possible optimum level of heterogeneity for the bone tissue. The homogeneous models demonstrated limited areas of damage with extensive crack formation. On the other hand, the heterogeneity in the material properties led to increased damage volume and a more variable distribution of damage compared to the homogeneous models. This resulted in uncracked regions which tended to have less damage accumulation preventing extensive crack propagation. The results also showed that the percent osteonal area was inversely correlated with crack volume and more evenly distributed osteons led to a lower amount of crack growth for all levels of material heterogeneity. In summary, this study developed a new computational modeling approach that directly evaluated the influence of heterogeneity in elastic and fracture material properties on fracture resistance of cortical bone. The results established new information that showed the adverse effects of reduced heterogeneity on fracture resistance in cortical bone and demonstrated the nonlinear relationship between heterogeneity and fracture resistance. This new computational modeling approach provides a tool that can be used to improve the understanding of the effects of material level changes due to prolonged BP use on the overall bone fracture behavior. It may also bring additional insight into the causes of unusual fractures, such as AFF and their possible association with long term BP use.

Cathepsin K inhibition preserves compressive load in lumbar vertebrae of osteoporotic monkeys

“…The changes in mechanical properties, without concomitant changes in bone microstructure, suggest that important changes in bone material composition may contribute to the observed mechanical difference, further supported by the observed increase in calculated apparent yield and peak stress. Compositional changes in bone have been associated with osteoporosis, and heterogeneity of these measurements is also emerging as an important contributor to bone mechanical properties, and fragility fracture risk ( Lloyd et al, 2015 ; Boskey et al, 2016 ; Donnelly et al, 2012 ; Tai et al, 2007 ; Wang et al, 2016 ; Demirtas et al, 2016 ; Gourion-Arsiquaud et al, 2010 ; Vennin et al, 2017 ; Yao et al, 2011 ). Nano- to microscale bone heterogeneity likely plays a crucial role in understanding bone mechanical properties and their role in fracture-risk ( Lloyd et al, 2015 ; Boskey et al, 2016 ; Donnelly et al, 2012 ; Tai et al, 2007 ; Wang et al, 2016 ; Demirtas et al, 2016 ; Gourion-Arsiquaud et al, 2010 ; Vennin et al, 2017 ; Yao et al, 2011 ).…”

Effects of the basic multicellular unit and lamellar thickness on osteonal fatigue life

“…Certain alterations in osteon architecture associate with decreased bone quality and increased fracture risk (Ascenzi et al, 2016; Bajaj et al, 2014; Barth et al, 1992; Demirtas et al, 2016; Diab et al, 2005; Geissler et al, 2015; George and Vashishth, 2005). For example, canal size increases in osteoporosis leading to more porous tissue (Barth et al, 1992).…”

“…The heterogeneous makeup of the bone’s microstructure and lower-level hierarchy are generally attributed with the resistance of bone to fatigue and fracture. Remodeling restores heterogeneity, decreasing the local tissue age in the process (Abdel-Wahab et al, 2012; Ascenzi and Lomovtsev, 2006; Demirtas et al, 2016). …”

Crack propagation in cortical bone is affected by the characteristics of the cement line: a parameter study using an XFEM interface damage model

“…The stiffness for the matrix was measured under wet conditions. Symbols used in the table: ~ approximate value interpreted from figures; K G calculated from a reported stress intensity factor K , where G = K 2 / E , assuming E = 20 GPa (Koester et al 2008); T transverse osteons (crack parallel to osteons); L longitudinal osteons (crack perpendicular to osteons) a Faingold et al (2014); b Nyman et al (2006); c Rho et al (1999); d Rho et al (2002); e Mullins et al (2009); f Hengsberger et al (2002); g Skedros et al (2005); h Milovanovic et al (2018); i Burr et al (1988); j Montalbano and Feng (2011); k Chan et al (2009); l Gargac et al (2014); m Gustafsson et al (2018b); n Sun et al (2010); o Dong et al (2005); p Bigley et al (2006); q Norman et al (1995); r Zimmermann et al (2009); s Koester et al (2008); t Nalla et al (2005); u Mullins et al (2009); v Abdel-Wahab et al (2012); w Li et al (2013); x Vergani et al (2014); y Budyn and Hoc (2007); z Baptista et al (2016); aa Idkaidek and Jasiuk (2017); ab Wang et al (2017); ac Idkaidek and Jasiuk (2017); ad Budyn et al (2008); ae Demirtas et al (2016); af Rodriguez-Florez et al (2017); ag Giner et al (2017); ah Mischinski and Ural (2011); ai Nobakhti et al (2014)…”