The aim of this study was to quantify the biomechanical basis for vertebral fracture risk in elderly men and women. A bone is likely to fracture when the loads imposed are similar to or greater than its strength. To quantify this risk, we developed a fracture risk index (FRI) based on the ratio of the vertebral body compressive load and strength. Loads were determined by upper body weight, height, and the muscle moment arm, and strength was estimated from cross-sectional area (CSA) and volumetric bone mineral density (vBMD). With loads less than the strength of the bone, the FRI remains <1. For any given load, once bone strength diminishes due to a falling vBMD, the FRI will increase. Should FRI approach or exceed unity, structural failure of the vertebra is likely. We measured vertebral body CSA vBMD of the middle zone of third lumbar vertebra by lateral and posteroanterior (PA) scanning using dual-energy X-ray absorptiometry (DXA) and calculated vertebral compressive stress (load per unit area) in 327 healthy men and 686 healthy women and 26 men and 55 postmenopausal women with vertebral fractures. Activities that require forward bending of the upper body caused ∼10-fold more compressive stress on the vertebra compared with standing upright. Men and women had similar peak vBMD in young adulthood. Because men have greater stature than women, the loads imposed on the vertebral body are higher (3754 ± 65 N vs. 3051 ± 31 N; p < 0.001). However, because CSA also was higher in men than women, peak load per unit CSA (stress) did not differ by gender (317.4 ± 4.7 N/cm2 vs. 321.9 ± 3.3 N/cm2, NS). The FRI was similar in young men and women and well below unity (0.42 ± 0.02 vs. 0.43 ± 0.01; NS). Gender differences emerged during aging; CSA increased in both men and women but more so in men, so load per unit area (stress) diminished but more so in men than in women. vBMD decreased in both genders but less so in men. These changes were captured in the FRI, which increased by only 21% in men and by 102% in women so that only 9% of elderly men but 26% of elderly women had an FRI ≥ 1. Men and women with vertebral fractures had an FRI that was greater than or equal to unity (1.03 ± 0.13 vs. 1.35 ± 0.13; p < 0.05) and was 2.04 SD and 2.26 SD higher than age-matched men and women, respectively. In summary and conclusion, young men and women have a similar vBMD, vertebral stress, and FRI. During aging, CSA increases more, and vBMD decreases less in men than in women. Thus, fewer men than women are at risk for fracture because fewer men than women have these structural determinants of bone strength below a level at which the loads exceed the bone's ability to tolerate them. Men and women with vertebral fractures have FRIs that are equal to or exceed unity. The results show that a fracture threshold for vertebrae can be defined using established biomechanical principles; whether this approach has greater sensitivity and specificity than the current BMD T score of −2.5 SD is unknown.