Structural Determinants of Vertebral Fracture Risk

Authors

  • L Joseph Melton III MD,

    Corresponding author
    1. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    2. Division of Endocrinology, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    • Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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  • B Lawrence Riggs,

    1. Division of Endocrinology, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Tony M Keaveny,

    1. University of California, Berkeley, California, USA
    2. O.N. Diagnostics, Berkeley, California, USA
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    • Dr Keaveny has a financial interest in O.N. Diagnostics, and both he and the company may benefit from the results of this research. Mr Hoffmann has equity interests in and is an employee of O.N. Diagnostics. The other authors state that they have no conflicts of interest.

  • Sara J Achenbach,

    1. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Paul F Hoffmann,

    1. O.N. Diagnostics, Berkeley, California, USA
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  • Jon J Camp,

    1. Biomedical Imaging Resource, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Peggy A Rouleau,

    1. Division of Computed Tomography, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Mary L Bouxsein,

    1. Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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  • Shreyasee Amin,

    1. Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Elizabeth J Atkinson,

    1. Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Richard A Robb,

    1. Biomedical Imaging Resource, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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  • Sundeep Khosla

    1. Division of Endocrinology, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Abstract

Vertebral fractures are more strongly associated with specific bone density, structure, and strength parameters than with areal BMD, but all of these variables are correlated.

Introduction: It is unclear whether the association of areal BMD (aBMD) with vertebral fracture risk depends on bone density per se, bone macro- or microstructure, overall bone strength, or spine load/bone strength ratios.

Materials and Methods: From an age-stratified sample of Rochester, MN, women, we identified 40 with a clinically diagnosed vertebral fracture (confirmed semiquantitatively) caused by moderate trauma (cases; mean age, 78.6 ± 9.0 yr) and compared them with 40 controls with no osteoporotic fracture (mean age, 70.9 ± 6.8 yr). Lumbar spine volumetric BMD (vBMD) and geometry were assessed by central QCT, whereas microstructure was evaluated by high-resolution pQCT at the ultradistal radius. Vertebral failure load (∼strength) was estimated from voxel-based finite element models, and the factor-of-risk (ϕ) was determined as the ratio of applied spine loads to failure load.

Results: Spine loading (axial compressive force on L3) was similar in vertebral fracture cases and controls (e.g., for 90° forward flexion, 2639 versus 2706 N; age-adjusted p = 0.173). However, fracture cases had inferior values for most bone density and structure variables. Bone strength measures were also reduced, and the factor-of-risk was 35–37% greater (worse) among women with a vertebral fracture. By age-adjusted logistic regression, relative risks for the strongest fracture predictor in each of the five main variable categories were bone density (total lumbar spine vBMD: OR per SD change, 2.2; 95% CI, 1.1–4.3), bone geometry (vertebral apparent cortical thickness: OR, 2.1; 95% CI, 1.1–4.1), bone microstructure (none significant); bone strength (“cortical” [outer 2 mm] compressive strength: OR, 2.5; 95% CI, 1.3–4.8), and factor-of-risk (ϕ for 90° forward flexion/overall vertebral compressive strength: OR, 3.2; 95% CI, 1.4–7.5). These variables were correlated with spine aBMD (partial r, −0.32 to 0.75), but each was a stronger predictor of fracture in the logistic regression analyses.

Conclusions: The association of aBMD with vertebral fracture risk is explained by its correlation with more specific bone density, structure, and strength parameters. These may allow deeper insights into fracture pathogenesis.

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