Heterogeneity and spatial distribution of intravertebral trabecular bone mineral density in the lumbar spine is associated with prevalent vertebral fracture

Kaiser, Jarred<sup>1</sup>; Allaire, Brett<sup>2</sup>; Fein, Paul M.<sup>1</sup>; Lu, Darlene<sup>3</sup>; Adams, Alexander<sup>1</sup>; Kiel, Douglas P<sup>2,4,5</sup>; Jarraya, Mohamed<sup>6,7</sup>; Guermazi, Ali<sup>6</sup>; Demissie, Serkalem<sup>3</sup>; Samelson, Elizabeth J.<sup>2,4,5</sup>; Bouxsein, Mary L.<sup>2,8</sup>; Morgan, Elise F.<sup>1</sup>

Affiliations

¹Department of Mechanical Engineering, Boston University, Boston, MA, USA

²Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

³Department of Biostatistics, Boston University, Boston, MA, USA

⁴Department of Medicine, Harvard Medical School, Boston, MA, USA

⁵Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Roslindale, MA, USA

⁶Department of Radiology, Boston University School of Medicine, Boston, MA, USA

⁷Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

⁸Department of Orthopedic Surgery, Harvard Medical School, Boston, MA, USA

Abstract and keywords

The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L3 vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5‐mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid‐transverse, and inferior/mid‐transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versu s165 ± 42 mg/cm3, p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture.

Keywords: BIOMECHANICS; BONE QCT/fiCT; FRACTURE RISK ASSESSMENT; GENERAL POPULATION STUDIES; OSTEOPOROSIS

Links

DOI: 10.1002/jbmr.3946

PubMed: 31886907

WoS: 000507432600001

History

Received: 2019-02-26

Revised: 2019-12-12

Accepted: 2019-12-14

Online: 2019-12-30

Cited Works (23)

Year	Entry
1999	Ebbesen EN, Thomsen JS, Beck‐Nielsen H, Nepper‐Rasmussen HJ, Mosekilde L. Age‐ and gender‐related differences in vertebral bone mass, density, and strength. J Bone Miner Res. August 1999;14(8):1394-1403.
2007	Kim D-G, Hunt CA, Zauel R, Fyhrie DP, Yeni YN. The effect of regional variations of the trabecular bone properties on the compressive strength of human vertebral bodies. Ann Biomed Eng. November 2007;35(11):1907-1913.
2010	Wegrzyn J, Roux J, Arlot ME, Boutroy S, Vilayphiou N, Guyen O, Delmas PD, Chapurlat R, Bouxsein ML. Role of trabecular microarchitecture and its heterogeneity parameters in the mechanical behavior of ex vivo human L3 vertebrae. J Bone Miner Res. November 2010;25(11):2324-2331.
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.
2012	Homminga J, Aquarius R, Bulsink VE, Jansen CTJ, Verdonschot N. Can vertebral density changes be explained by intervertebral disc degeneration? Med Eng Phys. May 2012;34(4):453-458.
2006	Nazarian A, Stauber M, Zurakowski D, Snyder BD, Müller R. The interaction of microstructure and volume fraction in predicting failure in cancellous bone. Bone. December 2006;39(6):1196-1202.
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.
1999	Ebbesen EN, Thomsen JS, Beck-Nielsen H, Nepper-Rasmussen HJ, Mosekilde L. Lumbar vertebral body compressive strength evaluated by dual-energy X-ray absorptiometry, quantitative computed tomography, and ashing. Bone. December 1999;25(6):713-724.
2001	Simpson EK, Parkinson IH, Manthey B, Fazzalari NL. Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine. J Bone Miner Res. April 2001;16(4):681-687.
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.
1996	Adams MA, McNally DS, Dolan P. "Stress" distributions inside intervertebral discs: the effects of age and degeneration. J Bone Joint Surg. November 1996;78B(6):965-972.
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	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.
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.
2002	Thomsen JS, Ebbesen EN, Mosekilde L. Zone-dependent changes in human vertebral trabecular bone: clinical implications. Bone. May 2002;30(5):664-669.
1995	McCubbrey DA, Cody DD, Peterson EL, Kuhn JL, Flynn MJ, Goldstein SA. Static and fatigue failure properties of thoracic and lumbar vertebral bodies and their relation to regional density. J Biomech. August 1995;28(8):891-899.
2013	Zysset PK, Dall'Ara E, Varga P, Pahr DH. Finite element analysis for prediction of bone strength. BoneKEy Rep. August 2013;2:386.
2011	Christiansen BA, Kopperdahl DL, Kiel DP, Keaveny TM, Bouxsein ML. Mechanical contributions of the cortical and trabecular compartments contribute to differences in age-related changes in vertebral body strength in men and women assessed by QCT-based finite element analysis. J Bone Miner Res. May 2011;26(5):974-983.
1991	Cody DD, Goldstein SA, Flynn MJ, Brown EB. Correlations between vertebral regional bone mineral density (rBMD) and whole bone fracture load. Spine. 1991;16(2):146-154.
2004	Pollintine P, Dolan P, Tobias JH, Adams MA. Intervertebral disc degeneration can lead to "stress-shielding" of the anterior vertebral body: a cause of osteoporotic vertebral fracture? Spine. April 1, 2004;29(7):774-782.
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.
1999	Yeh OC, Keaveny TM. Biomechanical effects of intraspecimen variations in trabecular architecture: a three-dimensional finite element study. Bone. August 1999;25(2):223-228.
2006	Bouxsein ML, Melton LJ III, Riggs BL, Muller J, Atkinson EJ, Oberg AL, Robb RA, Camp JJ, Rouleau PA, McCollough CH, Khosla S. Age‐ and sex‐specific differences in the factor of risk for vertebral fracture: a population‐based study using QCT. J Bone Miner Res. September 2006;21(9):1475-1482.

Cited By (2)

Year	Entry
2020	Auger JD, Frings N, Wu Y, Marty AG, Morgan EF. Trabecular architecture and mechanical heterogeneity effects on vertebral body strength. Curr Osteoporos Rep. December 2020;18(6):716-726.
2020	Jadzic J, Cvetkovic D, Milovanovic P, Tomanovic N, Zivkovic V, Nikolic S, Djuric M, Djonic D. The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis. Osteoporos Int. November 2020;31(11):2209-2217.