Voxel size and measures of individual resorption cavities in three-dimensional images of cancellous bone

Tkachenko, Evgeniy V.; Slyfield, Craig R.; Tomlinson, Ryan E.; Daggett, Justin; Wilson, David L.; Hernandez, Christopher J.

doi:10.1016/j.bone.2009.05.019

Cited by 22 publications

(30 citation statements)

References 22 publications

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“…Three-dimensional images of bone and fluorescent labels of microdamage were collected at a voxel size of 0.7 × 0.7 × 5.0 μm using serial milling (Slyfield et al, 2009; Slyfield et al, 2012; Tkachenko et al, 2009). As the image acquisition and pre-processing methodology has been well described previously (see Supplementary Materials for a summary), we concentrate here on image thresholding and analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The regions around each selected voxel (no regions overlapped) were displayed in three-dimensions to an observer blinded to the presence of microdamage. The observer then determined whether eroded surface was present within each region (Tkachenko et al, 2009). The proportion of voxels within microdamage with nearby eroded surface (p damage ) and the proportion of voxels distant from microdamage with nearby eroded surface (p no-damage ) were determined.…”

Section: Methodsmentioning

confidence: 99%

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The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

Lambers

Bouman

Tkachenko

et al. 2014

Journal of Biomechanics

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The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension v. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47–78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7 × 0.7 × 5.0 μm). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9 ± 2.4%, mean ± SD) than for apparent compression loading (1.9 ± 1.3%). Individual microdamage sites generated in tension were larger in volume (p < 0.001) but not more numerous (p = 0.64) than sites in compression. For both loading modes, the proportion of damaged tissue varied more across donors than with bone volume fraction, traditional measures of microarchitecture (trabecular thickness, trabecular separation, etc.), apparent Young's modulus, or strength. Microdamage tended to occur in regions of greater trabecular thickness but not near observable resorption cavities. Taken together, these findings indicate that, regardless of loading mode, accumulation of microdamage in cancellous bone after monotonic loading to yield is influenced by donor characteristics other than traditional measures of microarchitecture, suggesting a possible role for tissue material properties.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

Lambers

Bouman

Tkachenko

et al. 2014

Journal of Biomechanics

Self Cite

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show abstract

“…Although bone formation can be assessed using dynamic histomorphometry with double fluorochrome labeling, this technique is limited by its two-dimensional, destructive nature and its inability to quantify bone resorption. To improve the quantification of bone remodeling, a three- dimensional (3D) dynamic histomorphometry method has been developed that can simultaneously identify bone formation and resorption sites [22-26]. This method gives highly precise morphological measurements of bone formation and can indirectly measure resorption cavities; however, its destructive nature makes it difficult to longitudinally monitor disease progression or drug effects over multiple time points.…”

Section: Introductionmentioning

confidence: 99%

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy

Bakker¹,

Altman²,

Tseng³

et al. 2015

Bone

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Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r = 0.72 - 0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.

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“…In vivo dynamic bone histomorphometry has many strengths, including its ability to provide noninvasive, longitudinal measures. However, for applications where differences in bone remodeling rate are too low to be accurately distinguished from noise, alternate techniques should be used, such as the recently developed serial milling-based 3D histomorphometry technique 13, 19, 25-27 , which results in an in-plane resolution of 0.7 μm, allowing greater sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics

Bakker

Altman²,

et al. 2016

Ann Biomed Eng

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In vivo μCT imaging allows for high-resolution, longitudinal evaluation of bone properties. Based on this technology, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling. However, this analysis requires a direct voxel-by-voxel subtraction between image pairs, necessitating rotation of the images into the same coordinate system, which introduces interpolation errors. We developed a novel image transformation scheme, matched-angle transformation (MAT), whereby the interpolation errors are minimized by equally rotating both the follow-up and baseline images instead of the standard of rotating one image while the other remains fixed. This new method greatly reduced interpolation biases caused by the standard transformation. Additionally, our study evaluated the reproducibility and precision of bone remodeling measurements made via in vivo dynamic bone histomorphometry. Although bone remodeling measurements showed moderate baseline noise, precision was adequate to measure physiologically relevant changes in bone remodeling, and measurements had relatively good reproducibility, with intra-class correlation coefficients of 0.75-0.95. This indicates that, when used in conjunction with MAT, in vivo dynamic histomorphometry provides a reliable assessment of bone remodeling.

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Voxel size and measures of individual resorption cavities in three-dimensional images of cancellous bone

Cited by 22 publications

References 22 publications

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics

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