Improved estimates of strength and stiffness in pathologic vertebrae with bone metastases using CT-derived bone density compared with radiographic bone lesion quality classification

Abstract

Objective: The aim of this study was to compare the ability of 1) CT-derived bone lesion quality (classification of vertebral bone metastases [BM]) and 2) computed CT-measured volumetric bone mineral density (vBMD) for evaluating the strength and stiffness of cadaver vertebrae from donors with metastatic spinal disease.

Methods: Forty-five thoracic and lumbar vertebrae were obtained from cadaver spines of 11 donors with breast, esophageal, kidney, lung, or prostate cancer. Each vertebra was imaged using microCT (21.4 μm), vBMD, and bone volume to total volume were computed, and compressive strength and stiffness experimentally measured. The microCT images were reconstructed at 1-mm voxel size to simulate axial and sagittal clinical CT images. Five expert clinicians blindly classified the images according to bone lesion quality (osteolytic, osteoblastic, mixed, or healthy). Fleiss' kappa test was used to test agreement among 5 clinical raters for classifying bone lesion quality. Kruskal-Wallis ANOVA was used to test the difference in vertebral strength and stiffness based on bone lesion quality. Multivariable regression analysis was used to test the independent contribution of bone lesion quality, computed vBMD, age, gender, and race for predicting vertebral strength and stiffness.

Results: A low interrater agreement was found for bone lesion quality (κ = 0.19). Although the osteoblastic vertebrae showed significantly higher strength than osteolytic vertebrae (p = 0.0148), the multivariable analysis showed that bone lesion quality explained 19% of the variability in vertebral strength and 13% in vertebral stiffness. The computed vBMD explained 75% of vertebral strength (p < 0.0001) and 48% of stiffness (p < 0.0001) variability. The type of BM affected vBMD-based estimates of vertebral strength, explaining 75% of strength variability in osteoblastic vertebrae (R2 = 0.75, p < 0.0001) but only 41% in vertebrae with mixed bone metastasis (R2 = 0.41, p = 0.0168), and 39% in osteolytic vertebrae (R2 = 0.39, p = 0.0381). For vertebral stiffness, vBMD was only associated with that of osteoblastic vertebrae (R2 = 0.44, p = 0.0024). Age and race inconsistently affected the model's strength and stiffness predictions.

Conclusions: Pathologic vertebral fracture occurs when the metastatic lesion degrades vertebral strength, rendering it unable to carry daily loads. This study demonstrated the limitation of qualitative clinical classification of bone lesion quality for predicting pathologic vertebral strength and stiffness. Computed CT-derived vBMD more reliably estimated vertebral strength and stiffness. Replacing the qualitative clinical classification with computed vBMD estimates may improve the prediction of vertebral fracture risk.

Keywords: bone mineral density; mechanical testing; oncology; prediction of pathologic vertebral mechanics; radiographic classification; vertebral bone metastases.

FIG. 1.

Box-and-whisker plot of the computed vBMD (A) and bone fraction (B; BV/TV) of the vertebral specimens grouped by the clinician classification of bone lesion quality. Vertebrae classified as osteoblastic and mixed show marked variation in vBMD (35.1% and 33.4%, respectively) and BV/TV (33.3% and 37.7%, respectively) compared to vertebrae classified as osteolytic (14.7% and 15.4%, respectively).

FIG. 2.

Experimental load-displacement example curves for vertebral bodies containing osteoblastic, mixed, and osteolytic BM. The corresponding CT axial image for each of the tested vertebrae is presented. Compared to the osteoblastic and mixed BM vertebrae, the osteolytic vertebrae show reduced strength (vertebral strength, computed as the maximal force value recorded for the test) and stiffness (vertebral stiffness, computed from the coefficient of the linear regression model fitted to the linear portion of the load-displacement curve). Although the osteoblastic vertebrae demonstrated markedly higher vertebral strength than the mixed BM vertebrae, there is little difference in their respective vertebral stiffness values.

FIG. 3.

Regression analysis demonstrates the BM effect on the association of vertebral compressive strength with stiffness for each bone lesion category, with the association statistically significant for osteoblastic vertebrae only (A). Regression models and 95% confidence curves are presented for each bone metastasis type.

FIG. 4.

Box-and-whisker plot of the vertebral strength (A) and stiffness (B) grouped by the bone lesion quality classification. The ability of bone lesion quality to evaluate vertebral strength was limited to only the difference between osteoblastic and osteolytic vertebrae.

FIG. 5.

vBMD is a predictor of vertebral strength (A) and vertebral stiffness (B). Within individual BM types (C), the strength of prediction was maintained for osteoblastic vertebrae, while the prediction of strength was lower for vertebrae with mixed and osteolytic BM. For vertebral stiffness (D), although the prediction strength was maintained for osteoblastic and mixed BM vertebrae, bone density was weakly associated with osteolytic vertebral stiffness, suggesting that other mechanisms other than bone tissue density affect the structural response of osteolytic vertebrae.