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Item type:Publication, Access status: without files , Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element ModelingMultiple 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 T12 (T11 if T12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm 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: R2 = 0.57, yield force: R2 = 0.59, work to yield: R2 = 0.50, p < 0.001), BV/TV (stiffness: R2 = 0.56, yield force: R2 = 0.58, work to yield: R2 = 0.49, p < 0.001), and Tb.Sp (stiffness: R2 = 0.51, yield force: R2 = 0.53, work to yield: R2 = 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. © 2016 American Society for Bone and Mineral Research.Publicationtype: Journal Article214 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Administration of romosozumab improves vertebral trabecular and cortical bone as assessed with quantitative computed tomography and finite element analysis(Elsevier, 2015-07-29); ; ; ; Romosozumab inhibits sclerostin, thereby increasing bone formation and decreasing bone resorption. This dual effect of romosozumab leads to rapid and substantial increases in areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA). In a phase 1b, randomized, double-blind, placebo-controlled study, romosozumab or placebo was administered to 32 women and 16 men with low aBMD for 3. months, with a further 3-month follow-up: women received six doses of 1 or 2. mg/kg every 2. weeks (Q2W) or three doses of 2 or 3. mg/kg every 4. weeks (Q4W); men received 1. mg/kg Q2W or 3. mg/kg Q4W. Quantitative computed tomography (QCT) scans at lumbar (L1-2) vertebrae and high-resolution QCT (HR-QCT) scans at thoracic vertebra (T12) were analyzed in a subset of subjects at baseline, month 3, and month 6. The QCT subset included 24 romosozumab and 9 placebo subjects and the HR-QCT subset included 11 romosozumab and 3 placebo subjects. The analyses pooled the romosozumab doses. Linear finite element modeling of bone stiffness was performed. Compared with placebo, the romosozumab group showed improvements at month 3 for trabecular BMD by QCT and HR-QCT, HR-QCT trabecular bone volume fraction (BV/TV) and separation, density-weighted cortical thickness, and QCT stiffness (all p<. 0.05). At month 6, improvements from baseline were observed in QCT trabecular BMD and stiffness, and in HR-QCT BMD, trabecular BV/TV and separation, density-weighted cortical thickness, and stiffness in the romosozumab group (all p<. 0.05 compared with placebo). The mean (SE) increase in HR-QCT stiffness with romosozumab from baseline was 26.9%. ±. 6.8% and 35.0%. ±. 6.8% at months 3 and 6, respectively; subjects administered placebo had changes of -. 2.7%. ±. 13.4% and -. 6.4%. ±. 13.4%, respectively. In conclusion, romosozumab administered for 3. months resulted in rapid and large improvements in trabecular and cortical bone mass and structure as well as whole bone stiffness, which continued 3. months after the last romosozumab dose.Publicationtype: Journal ArticleScopus© Citations 54 27