Prediction of new clinical vertebral fractures in elderly men using finite element analysis of CT scans

Vertebral strength, as estimated by finite element analysis of computed tomography (CT) scans, has not yet been compared against areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) for prospectively assessing the risk of new clinical vertebral fractures. To do so, we conducted a case-cohort analysis of 306 men aged 65 years and older, which included 63 men who developed new clinically-identified vertebral fractures and 243 men who did not, all observed over an average of 6.5 years. Nonlinear finite element analysis was performed on the baseline CT scans, blinded to fracture status, to estimate L1 vertebral compressive strength and a load-to-strength ratio. Volumetric BMD by quantitative CT and areal BMD by DXA were also evaluated. We found that, for the risk of new clinical vertebral fracture, the age-adjusted hazard ratio per standard deviation change for areal BMD (3.2; 95% confidence interval [CI], 2.0-5.2) was significantly lower (p<0.005) than for strength (7.2; 95% CI, 3.6-14.1), numerically lower than for volumetric BMD (5.7; 95% CI, 3.1-10.3), and similar for the load-to-strength ratio (3.0; 95% CI, 2.1-4.3). After also adjusting for race, body mass index (BMI), clinical center, and areal BMD, all these hazard ratios remained highly statistically significant, particularly those for strength (8.5; 95% CI, 3.6-20.1) and volumetric BMD (9.4; 95% CI, 4.1-21.6). The area-under-the-curve for areal BMD (AUC=0.76) was significantly lower than for strength (AUC=0.83, p=0.02), volumetric BMD (AUC=0.82, p=0.05), and the load-to-strength ratio (AUC=0.82, p=0.05). We conclude that, compared to areal BMD by DXA, vertebral compressive strength and volumetric BMD consistently improved vertebral fracture risk assessment in this cohort of elderly men.