Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T-12 (T-11 if T-12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (-15.2%; p=0.010; sOR=1.73; 95% CI, 1.11 to 2.70), yield force (-21.5%; p=0.002; sOR=2.09; 95% CI, 1.27 to 3.43), and work to yield (-27.4%; p=0.001; sOR=2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R-2=0.57, yield force: R-2=0.59, work to yield: R-2=0.50, p < 0.001), BV/TV (stiffness: R-2=0.56, yield force: R-2=0.58, work to yield: R-2=0.49, p < 0.001), and Tb.Sp (stiffness: R-2=0.51, yield force: R-2=0.53, work to yield: R-2=0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. (c) 2016 American Society for Bone and Mineral Research

Association of QCT Bone Mineral Density and Bone Structure With Vertebral Fractures in Patients With Multiple Myeloma

Computed tomography (CT) is used for staging osteolytic lesions and detecting fractures in patients with multiple myeloma (MM). In the OsteoLysis of Metastases and Plasmacell-infiltration Computed Tomography 2 study (OLyMP-CT) study we investigated whether patients with and without vertebral fractures show differences in bone mineral density (BMD) or microstructure that could be used to identify patients at risk for fracture. We evaluated whole-body CT scans in a group of 104 MM patients without visible osteolytic lesions using an underlying lightweight calibration phantom (Image Analysis Inc., Columbia, KY, USA). QCT software (StructuralInsight) was used for the assessment of BMD and bone structure of the T-11 or T-12 vertebral body. Age-adjusted standardized odds ratios (sORs) per SD change were derived from logistic regression analyses, and areas under the receiver operating characteristics (ROC) curve (AUCs) analyses were calculated. Forty-six of the 104 patients had prevalent vertebral fractures (24/60 men, 22/44 women). Patients with fractures were not significantly older than patients without fractures (mean +/- SD, 64 +/- 9.2 versus 62 +/- 12.3 years; p=0.4). Trabecular BMD in patients with fractures versus without fractures was 169 +/- 41 versus 192 +/- 51mg/cc (AUC=0.62 +/- 0.06, sOR=1.6 [1.1 to 2.5], p=0.02). Microstructural variables achieved optimal discriminatory power at bone thresholds of 150mg/cc. Best fracture discrimination for single microstructural variables was observed for trabecular separation (Tb.Sp) (AUC=0.72 +/- 0.05, sOR=2.4 (1.5 to 3.9), p<0.0001). In multivariate models AUCs improved to 0.77 +/- 0.05 for BMD and Tb.Sp, and 0.79 +/- 0.05 for Tb.Sp and trabecular thickness (Tb.Th). Compared to BMD values, these improvements of AUC values were statistically significant (p<0.0001). In MM patients, QCT-based analyses of bone structure derived from routine CT scans permit discrimination of patients with and without vertebral fractures. Rarefaction of the trabecular network due to plasma cell infiltration and osteoporosis can be measured. Deterioration of microstructural measures appear to be of value for vertebral fracture risk assessment and may indicate early stages of osteolytic processes not yet visible. (c) 2014 American Society for Bone and Mineral Research

Cortical thinning and accumulation of large cortical pores in the tibia reflect local structural deterioration of the femoral neck

Introduction: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck. Methods: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 mu m voxel size. Cortical thickness (Ct.Th-tibia), porosity (Ct.Po-tibia) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 mu m pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models. Results: Femur strength was associated with the total (vBMD(tot); R-2 = 0.23, p 100 mu m in tibial cortical bone (relCt.Po100 mu m-tibia) indicated higher Tb.Sp(FN) (R-2 = 0.36, p <0.01) and lower Tb.N-FN (R-2 = 0.45, p <0.01). Conclusion: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia

Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for 3 months, and had an areal bone mineral density (aBMD) T-score 1.5 standard deviations. Subjects received 20g/d teriparatide (n=45) or 35mg/week risedronate (n=47) for 18 months. Primary objective was to compare lumbar spine (L1L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p=0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005&lt;p&lt;0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p=0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate