Structural Determinants of Vertebral Fracture Risk

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 () was determined as the ratio of applied spine loads to failure load. Results: Spine loading (axial compressive force on L 3 ) was similar in vertebral fracture cases and controls (e.g., for 90°forward flexion, 2639 versus 2706 N; age-adjusted p ‫ס‬ 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 ( 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.

Trabecular Bone Mechanical Properties in Patients with Fragility Fractures

“…In fact, there is substantial overlap in density measures between fracture and nonfracture patients [9,11]. DXA does not provide information on volumetric density distribution, bone geometry, architecture, microstructure, or strength, parameters that have been found to be strong predictors of fracture [42]. Density, structure, and strength variables were highly correlated with spine aBMD, measured by DXA, but each was a stronger predictor of fracture in an age-adjusted logistic regression [42].…”

“…A recent study found that women with vertebral fractures had a slightly larger crosssectional area accompanied by greater endocortical area and lower apparent cortical thickness, as well as reduced compressive strength in the outer 2 mm of vertebral cortical bone [42]. By estimating overall vertebral strength before and after virtually removing the peripheral 2-mm layer of bone in a finite element model, it has been shown that the cortical compartment carried about one half of the compressive load in both fracture cases and controls [42]. Therefore, although this paper focuses primarily on trabecular bone contributions in determining fracture risk, it is important to remember that the macrostructural architecture of cortical bone plays a crucial role in contributing to bone integrity.…”

“…DXA does not provide information on volumetric density distribution, bone geometry, architecture, microstructure, or strength, parameters that have been found to be strong predictors of fracture [42]. Density, structure, and strength variables were highly correlated with spine aBMD, measured by DXA, but each was a stronger predictor of fracture in an age-adjusted logistic regression [42]. Furthermore, an analysis of bone structure and density interactions under different loading conditions revealed that the combination of bone loading estimates with skeletal strength parameters was more strongly associated with vertebral fracture risk than densitometry measure alone [42].…”

Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

“…Bone microarchitecture parameters measured by HR-pQCT have been found to be associated with prevalent fracture in postmenopausal women and older men independently of areal bone mineral density (aBMD) [1][2][3][4][5]. Bone strength, estimated using micro-finite element analysis (μFEA), was also associated with prevalent fracture [6][7][8][9][10][11][12][13][14]. Moreover, HR-pQCT has been used to assess age-related bone loss [15][16][17][18][19] and to monitor variations in microarchitecture parameters during osteoporosis treatments [20][21][22][23][24][25][26].…”

Association of Jumping Mechanography-Derived Indices of Muscle Function with Tibial Cortical Bone Geometry

“…Clearly, further research is needed to elucidate to what extent interventions addressing peak voluntary muscle force influence cortical bone geometry and fracture risk, as this would have an impact on rehabilitation programs or other interventions for patients with suspected bone deficits. Given the fact that fracture risk seems to be mainly predicted by cortical rather than overall bone size [43][44][45][46][47][48], we speculate that increasing peak voluntary muscle force would benefit bone health and fracture risk more than increasing (leg) lean mass.…”