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

Loundagin, Lindsay L.; Pohl, Andrew J.; Edwards, W. Brent

doi:10.1016/j.bone.2020.115647

Cited by 7 publications

(3 citation statements)

References 49 publications

(71 reference statements)

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“…Mechanical fatigue behavior was analyzed using a parametric survival analysis to account for the censored nature of the fatigue life data. Similar to our previous work, (40) variation in observed fatigue life was described using a log-normal accelerated failure time model of the form:…”

Section: Discussionmentioning

confidence: 99%

“…Mechanical fatigue behavior was analyzed using a parametric survival analysis to account for the censored nature of the fatigue life data. Similar to our previous work, ( 40 ) variation in observed fatigue life was described using a log‐normal accelerated failure time model of the form:

\log ((), T) goodbreak= β_{0} goodbreak+ β_{1} ∙ \log ((), σ_{peak}) goodbreak+ italicγZ goodbreak+ ([], additional covariate terms)

where T is the number of cycles to failure for a sample and

σ_{peak}

is the peak stress during cyclic loading. Variables

β_{0}

and

β_{1}

are model fit parameters.…”

Section: Methodsmentioning

confidence: 99%

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

Haider

Loundagin

Sawatsky

et al. 2023

J of Bone & Mineral Res

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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 AE interquartile range (IQR) fatigue life of 1987 AE 10593 cycles, while animals in the ALN, ALN-DMAb, and DMAb groups survived 9850 AE 13648 (+395% versus VEH), 10493 AE 16796 (+428%), and 14495 AE 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.

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Section: Discussionmentioning

confidence: 99%

“…Mechanical fatigue behavior was analyzed using a parametric survival analysis to account for the censored nature of the fatigue life data. Similar to our previous work, ( 40 ) variation in observed fatigue life was described using a log‐normal accelerated failure time model of the form:

\log ((), T) goodbreak= β_{0} goodbreak+ β_{1} ∙ \log ((), σ_{peak}) goodbreak+ italicγZ goodbreak+ ([], additional covariate terms)

where T is the number of cycles to failure for a sample and

σ_{peak}

is the peak stress during cyclic loading. Variables

β_{0}

and

β_{1}

are model fit parameters.…”

Section: Methodsmentioning

confidence: 99%

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

Haider

Loundagin

Sawatsky

et al. 2023

J of Bone & Mineral Res

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show abstract

“…(26,27) Pores amplify local stress profiles and create stress concentrations that may facilitate the initiation and propagation of microcracks through bone tissue. (48,49) Pores located near the periosteal surface, the site of maximum stress under bending loads, (50) superimpose high local stress profiles over high bending stress. Therefore, the longitudinal increases in porosity observed preferentially in the mid-cortical and periosteal regions in this study could increase the risk of fragility fractures in patients undergoing RYGB.…”

Section: Discussionmentioning

confidence: 99%

Cortical Bone Loss Following Gastric Bypass Surgery Is Not Primarily Endocortical

Sadoughi

Pasco

Joseph

et al. 2020

Journal of Bone and Mineral Research

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Roux-en Y gastric bypass (RYGB) surgery is an effective treatment for obesity; however, it may negatively impact skeletal health by increasing fracture risk. This increase may be the result not only of decreased bone mineral density but also of changes in bone microstructure, for example, increased cortical porosity. Increased tibial and radial cortical porosity of patients undergoing RYGB surgery has been observed as early as 6 months postoperatively; however, local microstructural changes and associated biological mechanisms driving this increase remain unclear. To provide insight, we studied the spatial distribution of cortical porosity in 42 women and men (aged 46 AE 12 years) after RYGB surgery. Distal tibias and radii were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) preoperatively and at 12 months postoperatively. Laminar analysis was used to determine cortical pore number and size within the endosteal, midcortical, and periosteal layers of the cortex. Paired t tests were used to compare baseline versus follow-up porosity parameters in each layer. Mixed models were used to compare longitudinal changes in laminar analysis outcomes between layers. We found that the midcortical (0.927 AE 0.607 mm À2 to 1.069 AE 0.654 mm À2 , p = 0.004; 0.439 AE 0.293 mm À2 to 0.509 AE 0.343 mm À2 , p = 0.03) and periosteal (0.642 AE 0.412 mm À2 to 0.843 AE 0.452 mm À2 , p < 0.0001; 0.171 AE 0.101 mm À2 to 0.230 AE 0.160 mm À2 , p = 0.003) layers underwent the greatest increases in porosity over the 12-month period at the distal tibia and radius, respectively. The endosteal layer, which had the greatest porosity at baseline, did not undergo significant porosity increase over the same period (1.234 AE 0.402 mm À2 to 1.259 AE 0.413 mm À2 , p = 0.49; 0.584 AE 0.290 mm À2 to 0.620 AE 0.299 mm À2 , p = 0.35) at the distal tibia and radius, respectively. An alternative baseline-mapping approach for endosteal boundary definition confirmed that cortical bone loss was not primarily endosteal. These findings indicate that increases in cortical porosity happen in regions distant from the endosteal surface, suggesting that the underlying mechanism driving the increase in cortical porosity is not merely endosteal trabecularization.

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Bringing Mechanical Context to Image-Based Measurements of Bone Integrity

Loundagain

Bredbenner

Jepsen

et al. 2021

Curr Osteoporos Rep

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

Cited by 7 publications

References 49 publications

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

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

Cortical Bone Loss Following Gastric Bypass Surgery Is Not Primarily Endocortical

Bringing Mechanical Context to Image-Based Measurements of Bone Integrity

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