Stressed volume around vascular canals explains compressive fatigue life variation of secondary osteonal bone but not plexiform bone

The fatigue life of bone illustrates a large degree of scatter that is likely related to underlying differences in composition and microarchitecture. Vascular canals act as stress concentrations, the magnitude and volume of which may depend on the size and spatial distribution of canals. The purpose of this study was to establish the relationship between vascular canal microarchitecture, stressed volume and the fatigue life of both secondary osteonal and plexiform bovine bone. Twenty-one cortical bone samples were prepared from bovine femora and tibiae and imaged using micro-computed tomography (μCT) to quantify canal diameter, canal separation and canal number. Samples were cyclically loaded in zero-compression to a peak magnitude of 95 MPa, and fatigue life was defined as the number of cycles until fracture. Finite element models were created from μCT images and used to quantify the stressed volume, i.e., the volume of bone stressed higher than a yield stress of 108 MPa. Fatigue life ranged from 162-633,437 cycles with the fatigue life of plexiform bone (n = 15) being more than 4.5 times longer than secondary bone (n = 6). The fatigue life of secondary bone was negatively correlated with canal diameter (r2 = 0.73) and canal separation (r2 = 0.56), while the fatigue life of plexiform bone was negatively correlated with canal separation (r2 = 0.41), but positively correlated with canal number (r2 = 0.36). Stressed volume was related to canal microarchitecture in secondary bone only, where canal diameters and canal separation were larger than approximately 50 μm and 200 μm, respectively. Consequently, stressed volume explained 89% of the fatigue life variance in secondary bone but was not related to the fatigue life of plexiform bone. These findings suggest that the volume of the stress concentration surrounding vascular canals is dictated by canal size and spacing and may play an important role in the fatigue failure of osteonal bone. We suspect that a larger stressed volume is more likely to encounter and facilitate the propagation of pre-existing microcracks, thereby leading to a reduction in fatigue life

Experimental validation of finite element predicted bone strain in the human metatarsal

Metatarsal stress fracture is a common injury observed in athletes and military personnel. Mechanical fatigue is believed to play an important role in the etiology of stress fracture, which is highly dependent on the resulting bone strain from the applied load. The purpose of this study was to validate a subject-specific finite element (FE) modeling routine for bone strain prediction in the human metatarsal. Strain gauge measurements were performed on 33 metatarsals from seven human cadaveric feet subject to cantilever bending, and subject-specific FE models were generated from computed tomography images. Material properties for the FE models were assigned using a published density-modulus relationship as well as density-modulus relationships developed from optimization techniques. The optimized relationships were developed with a 'training set' of metatarsals (n=17) and cross-validated with a 'test set' (n=16). The published and optimized density elasticity equations provided FE-predicted strains that were highly correlated with experimental measurements for both the training (r2≥0.95) and test (r2≥0.94) sets; however, the optimized equations reduced the maximum error by 10% to 20% relative to the published equation, and resulted in an X=Y type of relationship between experimental measurements and FE predictions. Using a separate optimized density-modulus equation for trabecular and cortical bone did not improve strain predictions when compared to a single equation that spanned the entire bone density range. We believe that the FE models with optimized material property assignment have a level of accuracy necessary to investigate potential interventions to minimize metatarsal strain in an effort to prevent the occurrence of stress fracture.Natural Sciences and Engineering Research Council - Discovery Gran

Stressed volume estimated by finite element analysis predicts the fatigue life of human cortical bone: The role of vascular canals as stress concentrators

The fatigue life of cortical bone can vary several orders of magnitude, even in identical loading conditions. A portion of this variability is likely related to intracortical microarchitecture and the role of vascular canals as stress concentrators. The size, spatial distribution, and density of canals determine the peak magnitude and volume of stress concentrations. This study utilized a combination of experimental fatigue testing and image-based finite element (FE) analysis to establish the relationship between the stressed volume (i.e., volume of bone above yield stress) associated with vascular canals and the fatigue life of cortical bone. Thirty-six cortical bone samples were prepared from human femora and tibiae from five donors. Samples were allocated to four loading groups, corresponding to stress ranges of 60, 70, 80, and 90 MPa, then cyclically loaded in zero-compression until fracture. Porosity, canal diameter, canal separation, and canal number for each sample was quantified using X-ray microscopy (XRM) after testing. FE models were created from XRM images and used to calculate the stressed volume. Stressed volume was a good predictor of fatigue life, accounting for 67% of the scatter in fatigue-life measurements. An increase in stressed volume was most strongly associated with higher levels of intracortical porosity and larger canal diameters. The findings from this study suggest that a large portion of the fatigue-life variance of cortical bone in zero-compression is driven by intracortical microarchitecture, and that fatigue failure may be predicted by quantifying the stress concentrations associated with vascular canals

Mechanical fatigue of bovine cortical bone using ground reaction force waveforms in running

Stress fractures are a common overuse injury among runners associated with the mechanical fatigue of bone. Several in vivo biomechanical studies have investigated specific characteristics of the vertical ground reaction force (vGRF) in heel-toe running and have observed an association between increased loading rate during impact and individuals with a history of stress fracture. The purpose of this study was to examine the fatigue behavior of cortical bone using vGRF-like loading profiles, including those that had been decomposed into their respective impact and active phase components. Thirty-eight cylindrical cortical bone samples were extracted from bovine tibiae and femora. Hydrated samples were fatigue tested at room temperature in zero compression under load control using either a raw (n = 10), active (n = 10), low impact (n = 10), or high impact (n = 8) vGRF profile. The number of cycles to failure was quantified and the test was terminated if the sample survived 105 cycles. Fatigue life was significantly greater for both impact groups compared to the active (p < 0.001) and raw (p < 0.001) groups, with all low impact samples and 6 of 8 high impact samples surviving 105 cycles. The mean (± SD) number of cycles to failure for the active and raw groups was 12,133±11,704 and 16,552±29,612, respectively. The results suggest that loading rates associated with the impact phase of a typical vGRF in running have little influence on the mechanical fatigue behavior of bone relative to loading magnitude, warranting further investigation of the mechanism by which increased loading rates are associated with stress fracture.Natural Sciences and Engineering Research Council - Discovery Gran

Effects of footwear and stride length on metatarsal strains and failure in running

The metatarsal bones of the foot are particularly susceptible to stress fracture owing to the high strains they experience during the stance phase of running. Shoe cushioning and stride length reduction represent two potential interventions to decrease metatarsal strain and thus stress fracture risk.Natural Sciences and Engineering Research Council - Discovery Gran

Twelve Months of Denosumab and/or Alendronate Is Associated With Improved Bone Fatigue Life, Microarchitecture, and Density in Ovariectomized Cynomolgus Monkeys

Prolonged use of antiresorptives such as the bisphosphonate alendronate (ALN) and the RANKL inhibitor denosumab (DMAb) are associated with rare cases of atypical femoral fracture (AFF). The etiology of AFF is unclear, but it has been hypothesized that potent osteoclast inhibitors may reduce bone fatigue resistance. The purpose of this study was to quantify the relationship between antiresorptive treatment and fatigue life (cycles to failure) in bone from ovariectomized cynomolgus monkeys. We analyzed humeral bone from 30 animals across five treatment groups. Animals were treated for 12 months with subcutaneous (sc) vehicle (VEH), sc DMAb (25 mg/kg/month), or intravenous (iv) ALN (50 μg/kg/month). Another group received 6 months VEH followed by 6 months DMAb (VEH-DMAb), and the final group received 6 months ALN followed by 6 months DMAb (ALN-DMAb). A total of 240 cortical beam samples were cyclically tested in four-point bending at 80, 100, 120, or 140 MPa peak stress. High-resolution imaging and density measurements were performed to evaluate bone microstructure and composition. Samples from the ALN (p = 0.014), ALN-DMAb (p = 0.008), and DMAb (p < 0.001) groups illustrated higher fatigue-life measurements than VEH. For example, at 140 MPa the VEH group demonstrated a median ± interquartile range (IQR) fatigue life of 1987 ± 10593 cycles, while animals in the ALN, ALN-DMAb, and DMAb groups survived 9850 ± 13648 (+395% versus VEH), 10493 ± 16796 (+428%), and 14495 ± 49299 (+629%) cycles, respectively. All antiresorptive treatment groups demonstrated lower porosity, smaller pore size, greater pore spacing, and lower number of canals versus VEH (p < 0.001). Antiresorptive treatment was also associated with greater apparent density, dry density, and ash density (p ≤ 0.03). We did not detect detrimental changes following antiresorptive treatments that would explain their association with AFF. In contrast, 12 months of treatment may have a protective effect against fatigue fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/176049/1/jbmr4758.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/176049/2/jbmr4758_am.pd