Cortical indices, DXA, and FRAX as indicators of bone fragility: a comparative human cadaveric study

Abstract Osteoporosis (OP) is a progressive skeletal disorder characterized by reduced BMD and increased risk of fragility fractures. Clinical assessment relies primarily on DXA and the fracture risk assessment tool (FRAX), but limited access and low screening rates motivate investigation of complementary approaches. This human cadaveric study evaluated cortical indices of the second metacarpal, radius, and femur in relation to DXA-based OP status and biomechanically derived fracture susceptibility at the wrist and hip. Cortical measurements were obtained from 39 donor-matched forearms and femurs categorized as normal (n = 8), osteopenic (n = 11), and osteoporotic (n = 20) based on femoral neck (FN) DXA T-score. Simulated fall testing of the distal radius and proximal femur was performed to determine work to fracture, which was used to derive low and high biomechanical fracture susceptibility classifications. Among the cortical indices, metacarpal cortical index (MCI) demonstrated the strongest associations with DXA T-scores and biomechanical outcomes. MCI distinguished normal from osteoporotic classification at the FN (area under the curve [AUC] = 0.938) and 1/3 radius (AUC = 0.986). For biomechanically derived fracture susceptibility, FN T-score demonstrated strong discrimination at both the femur (AUC = 0.917) and wrist (AUC = 0.851), while MCI yielded AUCs of 0.847 and 0.855, respectively. FRAX hip fracture probability yielded AUCs of 0.911 at the femur and 0.830 at the wrist. These findings demonstrate associations between MCI, DXA-based OP status, and biomechanical fracture susceptibility in this cadaveric cohort. MCI may therefore warrant further investigation as a complementary screening approach, particularly where access to DXA is limited. Validation in larger clinical cohorts with prospective fracture outcomes is needed to determine its clinical utility.