Impact Microindentation Evaluates Bone Strength, Bone Quality, and Fracture Susceptibility Across Skeletal Sites: A Cadaver Study
Rachana S. Vaidya, Babak Jahani, James M. Jin, Christian C. Gonzalez, Bhanuteja Pujari, Siva Krothapalli, Simon Y. TangBackground
Impact microindentation (IMI) is a minimally invasive technique for assessing bone material properties that can be performed clinically. In this study, we aimed to determine how measurements obtained by IMI (bone material strength index [BMSi]) relate to bone strength, fracture resistance, and susceptibility to fracture.
Questions/purposes
(1) Is BMSi associated with bone strength of the femur, radius, and vertebrae, and does incorporating BMSi alongside bone mineral density (BMD) improve the estimation of strength? (2) Does BMSi evaluate fracture toughness and mechanical properties of the bone tissue? (3) Can BMSi discriminate fracture susceptibility of the hip and wrist?
Methods
This single-site laboratory study included the tibiae, femurs, radii, and L4 vertebrae from fresh-frozen cadavers (n = 67; mean ± SD age 71 ± 13 years). To answer the first question, IMI was performed on the tibia midshaft, dual-energy x-ray absorptiometry (DXA) was used to assess hip and spine BMD, and bone strength (ultimate fracture force) was mechanically determined for each site. To address the second question, stress intensity factor (K C ) was quantified from notched cortical bone beam specimens from tibiae using the fracture toughness test. Bone mechanical behavior (ultimate stress, elastic modulus, work-to-fracture), microstructure (cortical porosity, tissue mineral density), and organic matrix quality (percentage of collagen denaturation, concentration of advanced glycation end products) were quantified from beam specimens from the femoral midshaft. To address the last question, hip and wrist fracture susceptibility was defined using the fall-load to fracture-load ratio, where values ≥ 1 indicate susceptibility. Receiver operating characteristic (ROC) curve analyses evaluated the ability of IMI and DXA to discriminate fracture susceptibility. Primary outcomes included evaluating the association between BMSi and BMD with bone strength and ROC analysis for discriminating fracture susceptibility.
Results
Higher BMSi values were positively associated with higher bone strength, showing moderate association at the femur (r = 0.62 [95% confidence interval (CI) 0.49 to 0.72]; p < 0.001) and radius (r = 0.52 [95% CI 0.34 to 0.72]; p < 0.001) and weaker association at the L4 vertebrae (r = 0.31 [95% CI 0.03 to 0.53]; p = 0.02). At the femur, BMSi was more strongly associated with strength than total hip BMD (TH-BMD) (r = 0.45 [95% CI 0.3 to 0.62]; p < 0.001), and the inclusion of BMSi in multivariate analyses improved the explained variance in femur strength from 28% to 52% (ΔR 2 = 0.24; p < 0.001). At the radius, both BMSi and TH-BMD (r = 0.50 [95% CI 0.31 to 0.71]; p < 0.01) showed moderate association with radius strength, with the combined model improving the explained variance in radius strength from 28% to 39% (ΔR 2 = 0.11; p < 0.001). At the vertebrae, strength was weakly associated with BMSi (r = 0.31 [95% CI 0.03 to 0.53]; p = 0.02) but not with BMD. For the hip and wrist of each donor, BMSi discriminated hip fracture susceptibility with moderate accuracy (area under the curve [AUC] 0.75 [95% CI 0.63 to 0.88]; p < 0.001), whereas TH-BMD could not discriminate hip fracture susceptibility. Both BMSi (AUC 0.77 [95% CI 0.63 to 0.90]; p = 0.003) and TH-BMD (AUC 0.78 [95% CI 0.64 to 0.90]; p = 0.002) classified wrist fracture susceptibility with modest discriminatory performance.
Conclusion
Our study demonstrates that BMSi provides information related to bone strength and discriminates fracture susceptibility of the hip and wrist.
Clinical Relevance
IMI can be performed at the point of care using an FDA-cleared device and used to evaluate fragility in patients in whom fracture risk or bone strength is uncertain based on BMD alone. Prospective clinical studies are needed to determine whether IMI improves fracture risk prediction and informs patient treatment.