Opportunistic QCT Bone Mineral Density Measurements Predicting Osteoporotic Fractures: A Use Case in a Prospective Clinical Cohort.

Purpose: To assess whether volumetric vertebral bone mineral density (BMD) measured with opportunistic quantitative computed tomography (QCT) (i.e., CT acquired for other reasons) can predict osteoporotic fracture occurrence in a prospective clinical cohort and how this performs in comparison to dual-energy X-ray absorptiometry (DXA) measurements. Methods: In the database of our fracture liaison service, 58 patients (73 ± 11 years, 72% women) were identified that had at least one prevalent low-energy fracture and had undergone CT of the spine. BMD was determined by converting HU using scanner-specific conversion equations. Baseline DXA was available for 31 patients. During a 3-year follow-up, new fractures were diagnosed either by (i) recent in-house imaging or (ii) clinical follow-up with validated external reports. Associations were assessed using logistic regression models, and cut-off values were determined with ROC/Youden analyses. Results: Within 3 years, 20 of 58 patients presented new low-energy fractures (34%). Mean QCT BMD of patients with fractures was significantly lower (56 ± 20 vs. 91 ± 38 mg/cm3; p = 0.003) and age was higher (77 ± 10 vs. 71 ± 11 years; p = 0.037). QCT BMD was significantly associated with the occurrence of new fractures, and the OR for developing a new fracture during follow-up was 1.034 (95% CI, 1.010-1.058, p = 0.005), suggesting 3% higher odds for every unit of BMD decrease (1 mg/cm3). Age and sex showed no association. For the differentiation between patients with and without new fractures, ROC showed an AUC of 0.76 and a Youden's Index of J = 0.48, suggesting an optimal cut-off value of 82 mg/cm3. DXA T-scores showed no significant association with fracture occurrence in analogous regression models. Conclusion: In this use case, opportunistic BMD measurements attained through QCT predicted fractures during a 3-year follow-up. This suggests that opportunistic measurements are useful to reduce the diagnostic gap and evaluate the fracture risk in osteoporotic patients.

Osteoporosis imaging: effects of bone preservation on MDCT-based trabecular bone microstructure parameters and finite element models.

BACKGROUND: Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength due to a reduction of bone mass and deterioration of bone microstructure predisposing an individual to an increased risk of fracture. Trabecular bone microstructure analysis and finite element models (FEM) have shown to improve the prediction of bone strength beyond bone mineral density (BMD) measurements. These computational methods have been developed and validated in specimens preserved in formalin solution or by freezing. However, little is known about the effects of preservation on trabecular bone microstructure and FEM. The purpose of this observational study was to investigate the effects of preservation on trabecular bone microstructure and FEM in human vertebrae. METHODS: Four thoracic vertebrae were harvested from each of three fresh human cadavers (n=12). Multi-detector computed tomography (MDCT) images were obtained at baseline, 3 and 6 month follow-up. In the intervals between MDCT imaging, two vertebrae from each donor were formalin-fixed and frozen, respectively. BMD, trabecular bone microstructure parameters (histomorphometry and fractal dimension), and FEM-based apparent compressive modulus (ACM) were determined in the MDCT images and validated by mechanical testing to failure of the vertebrae after 6 months. RESULTS: Changes of BMD, trabecular bone microstructure parameters, and FEM-based ACM in formalin-fixed and frozen vertebrae over 6 months ranged between 1.0-5.6% and 1.3-6.1%, respectively, and were not statistically significant (p>0.05). BMD, trabecular bone microstructure parameters, and FEM-based ACM as assessed at baseline, 3 and 6 month follow-up correlated significantly with mechanically determined failure load (r=0.89-0.99; p<0.05). The correlation coefficients r were not significantly different for the two preservation methods (p>0.05). CONCLUSIONS: Formalin fixation and freezing up to six months showed no significant effects on trabecular bone microstructure and FEM-based ACM in human vertebrae and may both be used in corresponding in-vitro experiments in the context of osteoporosis.

Association of MRS-Based Vertebral Bone Marrow Fat Fraction with Bone Strength in a Human In Vitro Model.

Bone marrow adiposity has recently gained attention due to its association with bone loss pathophysiology. In this study, ten vertebrae were harvested from fresh human cadavers. Trabecular BMD and microstructure parameters were extracted from MDCT. Bone marrow fat fractions were determined using single-voxel MRS. Failure load (FL) values were assessed by destructive biomechanical testing. Significant correlations (P < 0.05) were observed between MRS-based fat fraction and MDCT-based parameters (up to r = -0.72) and MRS-based fat fraction and FL (r = -0.77). These findings underline the importance of the bone marrow in the pathophysiology and imaging diagnostics of osteoporosis.

X-ray dark-field vector radiography-a novel technique for osteoporosis imaging.

X-ray dark-field vector radiography (XVR) has emerged as an imaging technique which can efficiently yield dark-field scatter images of high quality, even with conventional X-ray tube sources. The XVR yields direction-dependent information about the X-ray scattering of the trabecular bone microstructure without the requirement of resolving the micrometer size structures directly causing the scattering. In this pilot study, we demonstrated that XVR-based degree of anisotropy correlated with femoral bone strength in the context of osteoporosis.

Prediction of vertebral failure load by using x-ray vector radiographic imaging.

PURPOSE: To examine whether x-ray vector radiographic (XVR) parameters could predict the biomechanically determined vertebral failure load. MATERIALS AND METHODS: Local institutional review boards approved the study and donors provided written informed consent before death. Twelve thoracic vertebral bodies were removed from three human cadavers and embedded in resin. XVR measurements were performed by using a Talbot-Lau grating interferometer with the beam direction in anterior-posterior and lateral direction. The mean anisotropy and the mean local average scattering power were calculated for a region of interest within each vertebra. Trabecular bone mineral density (BMD) was determined in each vertebra by using a clinical multidetector computed tomographic scanner. Failure load of the vertebral bodies was determined from destructive biomechanical tests. Statistical analyses were performed with statistical software with a two-sided Pvalue of .05 to calculate Pearson correlation coefficients and multiple regression model. RESULTS: Statistically significant correlations (P < .05) for failure load with XVR parameters in the lateral direction (r = -0.84 and 0.68 for anisotropy and local average scattering power, respectively) and for failure load and anisotropy in anteroposterior direction (r = -0.65) were found. A multiple regression model showed that the combination of the local average scattering power in lateral direction and BMD predicted failure load significantly better than BMD alone (adjusted R = 0.88 compared with 0.78, respectively; P < .001). CONCLUSION: The study results imply that XVR can improve the prediction of osteoporosis.