Biomechanical computed tomography analysis (BCT) for clinical assessment of osteoporosis

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Keaveny, T. M.¹; Clarke, B. L.²; Cosman, F.³; Orwoll, E. S.⁴; Siris, E. S.⁵; Khosla, S.²; Bouxsein, M. L.⁶

Biomechanical computed tomography analysis (BCT) for clinical assessment of osteoporosis

Osteoporos Int. June 2020;31(6):1025-1048

©2020 The Author(s)

Affiliations

¹Departments of Mechanical Engineering and Bioengineering, University of California, Berkeley, USA

²Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, USA

³Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA

⁴Bone and Mineral Unit, Oregon Health and Science University, Portland, USA

⁵Toni Stabile Osteoporosis Center, Department of Medicine, Columbia University Medical Center, New York, USA

⁶Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA
Abstract and keywords

The surgeon general of the USA defines osteoporosis as “a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture.” Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient’s clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied “opportunistically” to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication. For the BCT test, no modifications are required to standard clinical CT imaging protocols. The analysis provides measurements of bone strength as well as a dual-energy X-ray absorptiometry (DXA)–equivalent bone mineral density (BMD) T-score at the hip and a volumetric BMD of trabecular bone at the spine. Based on both the bone strength and BMD measurements, a physician can identify osteoporosis and assess fracture risk (high, increased, not increased), without needing confirmation by DXA. To help introduce BCT to clinicians and health care professionals, we describe in this review the currently available clinical implementation of the test (VirtuOst), its application for managing patients, and the underlying supporting evidence; we also discuss its main limitations and how its results can be interpreted clinically. Together, this body of evidence supports BCT as an accurate and convenient diagnostic test for osteoporosis in both sexes, particularly when used opportunistically for patients already with CT.

Mini Abstract: Biomechanical Computed Tomography analysis (BCT) uses a patient’s CT scan to measure both bone strength and bone mineral density at the hip or spine. Performing at least as well as DXA for both diagnosing osteoporosis and assessing fracture risk, BCT is particularly well-suited to “opportunistic” use for the patient without a recent DXA who is undergoing or has previously undergone CT testing (including hip or spine regions) for an unrelated medical condition.

Keywords: Biomechanical computed tomography; Bone mineral density; Bone strength; Finite element analysis; Fracture risk; Osteoporosis
Links

DOI: 10.1007/s00198-020-05384-2

PubMed: 32335687

WoS: 000528669400001
History

Received: 2019-11-27

Accepted: 2020-03-09

Online: 2020-04-26

Cited Works (45)

Year	Entry
1985	Cann CE, Genant HK, Kolb FO, Ettinger B. Quantitative computed tomography for prediction of vertebral fracture risk. Bone. 1985;6(1):1-7.
2020	Bouxsein ML, Zysset P, Glüer CC, McClung M, Biver E, Pierroz DD, Ferrari SL; IOF Working Group on Hip Bone Strength as a Therapeutic Target. Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk. Osteoporos Int. March 2020;31(3):393-408.
2010	Keaveny TM. Biomechanical computed tomography: noninvasive bone strength analysis using clinical computed tomography scans. Annals NY Acad Sci. 2010;1192(1):57-65.
2014	Nawathe S, Akhlaghpour H, Bouxsein ML, Keaveny TM. Microstructural failure mechanisms in the human proximal femur for sideways fall loading. J Bone Miner Res. February 2014;29(2):507-515.
2001	NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. February 14, 2001;285(6):785-795.
2004	Schuit SCE, van der Klift M, Weel AEAM, de Laet CEDH, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JPTM, Pols HAP. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. January 2004;34(1):195-202.
2007	Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA. Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of qct scans in women with osteoporosis. J Bone Miner Res. January 2007;22(1):149-157.
2007	Bolotin HH. DXA in vivo BMD methodology: an erroneous and misleading research and clinical gauge of bone mineral status, bone fragility, and bone remodelling. Bone. July 2007;41(1):138-154.
2008	Schileo E, Taddei F, Cristofolini L, Viceconti M. Subject-specific finite element models implementing a maximum principal strain criterion are able to estimate failure risk and fracture location on human femurs tested in vitro. J Biomech. 2008;41(2):356-367.
2002	Kopperdahl DL, Morgan EF, Keaveny TM. Quantitative computed tomography estimates of the mechanical properties of human vertebral trabecular bone. J Orthop Res. July 2002;20(4):801-805.
1991	Faulkner KG, Cann CE, Hasegawa BH. Effect of bone distribution on vertebral strength: assessment with patient-specific nonlinear finite element analysis. Radiology. June 1991;179(3):669-674.
2011	Dragomir-Daescu D, Op Den Buijs J, McEligot S, Dai Y, Entwistle RC, Salas C, Melton LJ III, Bennet KE, Khosla S, Amin S. Robust QCT/FEA models of proximal femur stiffness and fracture load during a sideways fall on the hip. Ann Biomed Eng. February 2011;39(2):742-755.
1998	Keyak JH, Rossi SA, Jones KA, Skinner HB. Prediction of femoral fracture load using automated finite element modeling. J Biomech. February 1998;31(2):125-133.
2008	Schileo E, Dall’Ara E, Taddei F, Malandrino A, Schotkamp T, Baleani M, Viceconti M. An accurate estimation of bone density improves the accuracy of subject-specific finite element models. J Biomech. August 7, 2008;41(11):2483-2491.
2008	Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, Felsenberg D, Ito M, Prevrhal S, Hans DB, Lewiecki EM. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD official positions. J Clin Densitom. January–March 2008;11(1):123-162.
2014	Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson‐Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. November 2014;29(11):2520-2526.
2004	Bayraktar HH, Morgan EF, Niebur GL, Morris GE, Wong EK, Keaveny TM. Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue. J Biomech. January 2004;37(1):27-35.
2007	Melton LJ III, Riggs BL, Keaveny TM, Achenbach SJ, Hoffmann PF, Camp JJ, Rouleau PA, Bouxsein ML, Amin S, Atkinson EJ, Robb RA, Khosla S. Structural determinants of vertebral fracture risk. J Bone Miner Res. December 2007;22(12):1885-1892.
2019	Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. May 2019;104(5):1595-1622.
1998	Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ; Fracture Intervention Trial Research Group. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. December 23, 1998;280(24):2077-2082.
2017	Johannesdottir F, Thrall E, Muller J, Keaveny TM, Kopperdahl DL, Bouxsein ML. Comparison of non-invasive assessments of strength of the proximal femur. Bone. December 1, 2017;105:93-102.
2010	Stein EM, Liu XS, Nickolas TL, Cohen A, Thomas V, McMahon DJ, Zhang C, Yin PT, Cosman F, Nieves J, Guo XE, Shane E. Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures. J Bone Miner Res. December 2010;25(12):2572-2581.
2009	Orwoll ES, Marshall LM, Nielson CM, Cummings SR, Lapidus J, Cauley JA, Ensrud K, Lane N, Hoffmann PR, Kopperdahl DL, Keaveny TM; Osteoporotic Fractures in Men (MrOS) Study Group. Finite element analysis of the proximal femur and hip fracture risk in older men. J Bone Miner Res. March 2009;24(3):475-483.
1995	Lotz JC, Cheal EJ, Hayes WC. Stress distributions within the proximal femur during gait and falls: implications for osteoporotic fracture. Osteoporos Int. July 1995;5(3):252-261.
2012	Yu EW, Thomas BJ, Brown JK, Finkelstein JS. Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT. J Bone Miner Res. January 2012;27(1):119-124.
2005	Wainwright SA, Marshall LM, Ensrud KE, Cauley JA, Black DM, Hillier TA, Hochberg MC, Vogt MT, Orwoll ES; Study of Osteoporotic Fractures Research Group. Hip fracture in women without osteoporosis. J Clin Endocrinol Metab. May 2005;90(5):2787-2793.
2007	Buckley JM, Loo K, Motherway J. Comparison of quantitative computed tomography-based measures in predicting vertebral compressive strength. Bone. March 2007;40(3):767-774.
2014	Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. October 2014;25(10):2359-2381.
2010	Keaveny TM, Kopperdahl DL, Melton LJ III, Hoffmann PF, Amin S, Riggs BL, Khosla S. Age‐dependence of femoral strength in white women and men. J Bone Miner Res. May 2010;25(5):994-1001.
2014	Kopperdahl DL, Aspelund T, Hoffmann PF, Sigurdsson S, Siggeirsdottir K, Harris TB, Gudnason V, Keaveny TM. Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans. J Bone Miner Res. March 2014;29(3):570-580.
2013	Keyak JH, Sigurdsson S, Karlsdottir GS, Oskarsdottir D, Sigmarsdottir A, Kornak J, Harris TB, Sigurdsson G, Jonsson BY, Siggeirsdottir K, Eiriksdottir G, Gudnason V, Lang TF. Effect of finite element model loading condition on fracture risk assessment in men and women: the AGES-Reykjavik study. Bone. November 2013;57(1):18-29.
2011	Amin S, Kopperdhal DL, Melton LJ, Achenbach SJ, Therneau TM, Riggs BL, Keaveny TM, Khosla S. Association of hip strength estimates by finite‐element analysis with fractures in women and men. J Bone Miner Res. July 2011;26(7):1593-1600.
2003	Crawford RP, Cann CE, Keaveny TM. Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography. Bone. 2003;33(4):744-750.
2013	Zysset PK, Dall'Ara E, Varga P, Pahr DH. Finite element analysis for prediction of bone strength. BoneKEy Rep. August 2013;2:386.
1999	Cody DD, Gross GJ, Hou FJ, Spencer HJ, Goldstein SA, Fyhrie DP. Femoral strength is better predicted by finite element models than QCT and DXA. J Biomech. October 1999;32(10):1013-1020.
2015	Zysset P, Qin L, Lang T, Khosla S, Leslie WD, Shepherd JA, Schousboe JT, Engelke K. Clinical use of quantitative computed tomography–based finite element analysis of the hip and spine in the management of osteoporosis in adults: the 2015 ISCD official positions—part II. J Clin Densitom. July–September 2015;18(3):359-392.
2001	Morgan EF, Keaveny TM. Dependence of yield strain of human trabecular bone on anatomic site. J Biomech. 2001;34(5):569-577.
2003	Morgan EF, Bayraktar HH, Keaveny TM. Trabecular bone modulus–density relationships depend on anatomic site. J Biomech. July 2003;36(7):897-904.
2013	Dall'Ara E, Luisier B, Schmidt R, Kainberger F, Zysset P, Pahr D. A nonlinear QCT-based finite element model validation study for the human femur tested in two configurations in vitro. Bone. January 2013;52(1):27-38.
2012	Wang X, Sanyal A, Cawthon PM, Palermo L, Jekir M, Christensen J, Ensrud KE, Cummings SR, Orwoll E, Black DM, Keaveny TM; Osteoporotic Fractures in Men (MrOS) Research Group. Prediction of new clinical vertebral fractures in elderly men using finite element analysis of CT scans. J Bone Miner Res. April 2012;27(4):808-816.
2008	Keaveny TM, Hoffmann PF, Singh M, Palermo L, Bilezikian JP, Greenspan SL, Black DM. Femoral bone strength and its relation to cortical and trabecular changes after treatment with PTH, alendronate, and their combination as assessed by finite element analysis of quantitative CT scans. J Bone Miner Res. December 2008;23(12):1974-1982.
2014	Schileo E, Balistreri L, Grassi L, Cristofolini L, Taddei F. To what extent can linear finite element models of human femora predict failure under stance and fall loading configurations? J Biomech. November 7, 2014;47(14):3531-3538.
2007	Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Glüer C, Goltzman D, Hans D, Krieg M-A, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott A-M, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. August 2007;18(8):1033-1046.
2012	Grassi L, Schileo E, Taddei F, Zani L, Juszczyk M, Cristofolini L, Viceconti M. Accuracy of finite element predictions in sideways load configurations for the proximal human femur. J Biomech. January 10, 2012;45(2):394-399.
2009	Bessho M, Ohnishi I, Matsumoto T, Ohashi S, Matsuyama J, Tobita K, Kaneko M, Nakamura K. Prediction of proximal femur strength using a CT-based nonlinear finite element method: differences in predicted fracture load and site with changing load and boundary conditions. Bone. August 2009;45(2):226-231.

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2021	Winsor C, Li X, Qasim M, Henak CR, Pickhardt PJ, Ploeg H, Viceconti M. Evaluation of patient tissue selection methods for deriving equivalent density calibration for femoral bone quantitative CT analyses. Bone. February 2021;143:115759.
2022	Fleps I, Pálsson H, Baker A, Enns-Bray W, Bahaloo H, Danner M, Singh NB, Taylor WR, Sigurdsson S, Gudnason V, Ferguson SJ, Helgason B. Finite element derived femoral strength is a better predictor of hip fracture risk than aBMD in the AGES Reykjavik study cohort. Bone. January 2022;154:116219.
2023	Song F, Wei Y, Feng W, Fu R, Li Z, Gao X, Cheng X, Yang H. Biomechanical CT-computed bone strength predicts the risk of subsequent vertebral fracture. Bone. January 2023;166:116601.
2023	Ganapathy A, Nieves JW, Keaveny TM, Cosman F. Effects of four-year cyclic versus two-year daily teriparatide treatment on volumetric bone density and bone strength in postmenopausal women with osteoporosis. Bone. February 2023;167:116618.
2023	Gao X, Din RU, Cheng X, Yang H. Biomechanical MRI detects reduced bone strength in subjects with vertebral fractures. Bone. August 2023;173:116810.
2020	Hong N, Lee DC, Khosla S, Keaveny TM, Rhee Y. Comparison of vertebral and femoral strength between white and asian adults using finite element analysis of computed tomography scans. J Bone Miner Res. December 2020;35(12):2345-2354.
2023	Pignolo RJ, Hsiao EC, Mukaddam MA, Baujat G, Berglund SK, Brown MA, Cheung AM, Cunto CD, Delai P, Haga N, Kannu P, Keen R, Sang K-HLQ, Mancilla EE, Marino R, Strahs A, Kaplan FS. Reduction of new heterotopic ossification (HO) in the open-label, phase 3 MOVE trial of palovarotene for fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. March 2023;38(3):381-394.
2023	Huber FA, Singhal V, Tuli S, Stanford FC, Carmine B, Bouxsein ML, Misra M, Bredella MA. Biomechanical CT to assess bone after sleeve gastrectomy in adolescents with obesity: a prospective longitudinal study. J Bone Miner Res. July 2023;38(7):933-942.
2023	Grassi L, Väänänen SP, Jehpsson L, Ljunggren Ö, Rosengren BE, Karlsson MK, Isaksson H. 3D finite element models reconstructed from 2D dual-energy x-ray absorptiometry (DXA) images improve hip fracture prediction compared to areal BMD in osteoporotic fractures in men (MrOS) Sweden cohort. J Bone Miner Res. September 2023;38(9):1258-1267.
2021	Gustafsson A, Tognini M, Bengtsson F, Gasser TC, Isaksson H, Grassi L. Subject-specific FE models of the human femur predict fracture path and bone strength under single-leg-stance loading. J Mech Behav Biomed Mater. January 2021;113:104118.
2020	Bonnheim N. Fundamental Mechanisms of Load Transfer in the Human Vertebral Body Following Lumbar Total Disc Arthroplasty [PhD thesis]. Berkeley, CA: Berkeley, University of California; 2020.
2022	Winsor C. Femoral Bone Quantitative CT Analyses With Internal Tissue-Based Phantomless Densitometric CT Calibration [PhD thesis]. University of Wisconsin – Madison; 2022.