Quantitative CT‐Based Methods for Bone Microstructural Measures and Their Relationships With Vertebral Fractures in a Pilot Study on Smokers

Abstract

Osteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT-based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra-high-resolution (UHR) CT and micro-CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5-year follow-up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT-derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro-CT-derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility-intra-class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non-fracture and fracture groups. Vertebral fracture-group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures-81.8% versus 63.2% for former smokers-the difference was not statistically significant. This pilot cross-sectional human study demonstrates CT-based peripheral bone microstructural differences among smokers with and without vertebral fractures.

Finite element analysis of trabecular bone microstructure using CT imaging and continuum mechanical modeling

“…Moreover, the CT images used in this study were acquired under a condition similar to in vivo imaging using a CT protocol previously applied on human studies. 27,45 Therefore, our experiments and results also validate continuum FEA methods for computing surrogate measures of Tb microstructural modulus using in vivo CT imaging of peripheral sites suitable for human studies. Large deviation in CT-derived modulus values as compared to micro-CT or mechanical test-derived results was observed, which suggests that CT-derived modulus values may not be used as actual modulus measures.…”

“…High linear correlation of CT‐derived modulus values using continuum FEA methods with micro‐CT and mechanical testing derived reference values suggests that the CT‐based continuum FEA is useful to obtain a surrogate modulus measure of Tb microstructure. Moreover, the CT images used in this study were acquired under a condition similar to in vivo imaging using a CT protocol previously applied on human studies 27,45 . Therefore, our experiments and results also validate continuum FEA methods for computing surrogate measures of Tb microstructural modulus using in vivo CT imaging of peripheral sites suitable for human studies.…”

“…The primary difference is the lack of movement artifacts in CT scans of cadaveric specimens; however, the motion artifacts are minimal for high‐speed CT imaging used here, which takes only 23.2 s to acquire a 10‐cm long scan of the tibia. Also, no motion artifact was observed in our recent studies involving in vivo CT scans of human subjects using similar protocols 20,27,49,50 . Another limitation of this study was that parallel platens testing was used to experimentally measure actual compressive modulus of Tb cores.…”

“…Also, no motion artifact was observed in our recent studies involving in vivo CT scans of human subjects using similar protocols. 20,27,49,50 Another limitation of this study was that parallel platens testing was used to experimentally measure actual compressive modulus of Tb cores. It has been previously demonstrated that platens compression testing underestimates Tb modulus measures.…”

“…Three CT scans were collected for each specimen after repositioning the specimen on the scanner table between each repeat scan. Ankle specimens were positioned using scanner‐provided laser beam reference as described by Zhang et al 27 …”