Fatigue-induced microdamage in cancellous bone occurs distant from resorption cavities and trabecular surfaces

Goff, M.G.; Lambers, Floor M.; Nguyen, Thu-Mai; Sung, Joon Hong; Rimnac, Clare M.; Hernandez, Christopher J.

doi:10.1016/j.bone.2015.05.020

Cited by 26 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In theory, that mechanism should be more pronounced in more highly porous bone . However, whether or not resorption‐related microcavities actually reduce overall bone strength at all is a biomechanically complex issue and remains a topic of ongoing research . Likewise, it is theoretically possible that treatment‐induced changes in tissue‐level ductility and microdamage could alter whole‐bone strength differentially in older osteoporotic humans compared with in cynos or large animals.…”

Section: Discussionmentioning

confidence: 99%

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys

Lee

Varela²,

Kostenuik

et al. 2016

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R 2 ¼ 0.97; n ¼ 52) with mechanical testing, independent of treatment (p ¼ 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p ¼ 0.79) between mechanical testing (þ57%; 95% CI [26%, 95%]) and finite element analysis (þ51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (þ45% [19%, 73%]) and trabecular bone volume fraction (þ24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation-developed for human bone and clinically validated in fracture-outcome studies-correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One implication is that the treatment effects in this study are well explained by the features contained within these finite element models, namely, the bone geometry and mass and the spatial distribution of bone mass.

show abstract

Section: Discussionmentioning

confidence: 99%

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys

Lee

Varela²,

Kostenuik

et al. 2016

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…The largest microdamage sites were spatially correlated with the largest regions of high tissue strain determined with finite element models. Therefore our findings demonstrate surprising effectiveness of linear elastic finite element models to predict the locations of the largest (and most biomechanically relevant (Goff et al, 2015)) microdamage sites.…”

Section: 0 Discussionmentioning

confidence: 59%

“…As large microdamage sites (sites over 1,000,000 μm 3 in volume) have been shown to be the most influential biomechanically (Goff et al, 2015), we also examined the spatial correlation assays looking only at large microdamage and highly strained tissue sites. Most of the microdamage volume (86% ± 8%) was located in a small number of large microdamage sites (microdamage sites exceeding 1,000,000 μm 3 in volume).…”

Section: 0 Resultsmentioning

confidence: 99%

Finite element models predict the location of microdamage in cancellous bone following uniaxial loading

Goff

Lambers

Sorna

et al. 2015

Journal of Biomechanics

Self Cite

View full text Add to dashboard Cite

High-resolution finite element models derived from micro-computed tomography images are often used to study the effects of trabecular microarchitecture and loading mode on tissue stress, but the degree to which existing finite element methods correctly predict the location of tissue failure is not well characterized. In the current study, we determined the relationship between the location of highly strained tissue, as determined from high-resolution finite element models, and the location of tissue microdamage, as determined from three-dimensional fluoroscopy imaging, which was performed after the microdamage was generated in-vitro by mechanical testing. Fourteen specimens of human vertebral cancellous bone were assessed (8 male donors, 2 female donors, 47–78 years of age). Regions of stained microdamage, were 50–75% more likely to form in highly strained tissue (principal strains exceeding 0.4%) than elsewhere, and generally the locations of the regions of microdamage were significantly correlated (p < 0.05) with the locations of highly strained tissue. This spatial correlation was stronger for the largest regions of microdamage (≥ 1,000,000 μm3 in volume); 87% of large regions of microdamage were located near highly strained tissue. Together, these findings demonstrate that there is a strong correlation between regions of microdamage and regions of high strain in human cancellous bone, particularly for the biomechanically more important large instances of microdamage.

show abstract

“…While pre-existing microdamage was an indicator of damage risk, consistent with findings in earlier studies (Hernandez et al, 2014), crack propagation was not a common mode of new damage. This tendency of bone to form new cracks rather than propagate existing cracks has been observed in both cortical (O'Brien et al, 2003) and trabecular bone (Goff et al, 2015; Wang, 2005; Wang and Niebur, 2006; Wu, 2013). Taken together, the evidence suggests that damage is more dependent on alterations in the stress field through the trabecular network than stress concentrations at existing damage, and that similar crack arrest mechanisms are active in both cortical and trabecular bone tissue.…”

Section: Discussionmentioning

confidence: 84%

The roles of architecture and estrogen depletion in microdamage risk in trabecular bone

Kreipke

Garrison

Easley

et al. 2016

Journal of Biomechanics

View full text Add to dashboard Cite

Bone quantity, or density, has insufficient power to discriminate fracture risk in individuals. Additional measures of bone quality, such as microarchitectural characteristics and bone tissue properties, including the presence of damage, may improve the diagnosis of fracture risk. Microdamage and microarchitecture are two aspects of trabecular bone quality that are interdependent, with several microarchitectural changes strongly correlated to damage risk after compensating for bone density. This study aimed to delineate the effects of microarchitecture and estrogen depletion on microdamage susceptibility in trabecular bone using an ovariectomized sheep model to mimic post-menopausal osteoporosis. The propensity for microdamage formation in trabecular bone of the distal femur was studied using a sequence of compressive and torsional overloads. Ovariectomy had only minor effects on the microarchitecture at this anatomic site. Microdamage was correlated to bone volume fraction and structure model index (SMI), and ovariectomy increased the sensitivity to these parameters. The latter may be due to either increased resorption cavities acting as stress concentrations or to altered bone tissue properties. Pre-existing damage was also correlated to new damage formation. However, sequential loading primarily generated new cracks as opposed to propagating existing cracks, suggesting that pre-existing microdamage contributes to further damage of bone by shifting load bearing to previously undamaged trabeculae, which are subsequently damaged. The transition from plate-like to rod-like trabeculae, indicated by SMI, dictates this shift, and may be a hallmark of bone that is already predisposed to accruing greater levels of damage through compromised microarchitecture.

show abstract

Fatigue-induced microdamage in cancellous bone occurs distant from resorption cavities and trabecular surfaces

Cited by 26 publications

References 42 publications

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys

Finite element models predict the location of microdamage in cancellous bone following uniaxial loading

The roles of architecture and estrogen depletion in microdamage risk in trabecular bone

Contact Info

Product

Resources

About