We used QCT scans obtained in 687 men and women, 21–97 years of age, to estimate the factor of risk for vertebral fracture, Φ_vert, defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Φ_vert increased significantly more in women than men. Age‐ and sex‐specific differences in Φ_vert closely resembled previously reported vertebral fracture incidence. Introduction: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility. Materials and Methods: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Φ_vert) in an age‐ and sex‐stratified population‐based sample of 700 women and men 21–97 years of age. We measured volumetric BMD (vBMD, mg/cm³) and cross‐sectional area (CSA, cm²) of the midvertebral bodies of L₁–L₃ using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L₃ vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Φ_vert, was computed as the ratio of spinal compressive force to vertebral strength for each activity. Results: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (−43% versus −31%, p = 0.008). Compressive forces on L₃ were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8‐fold higher than those experienced during upright standing. For all activities, Φ_vert increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Φ_{vert‐bending} exceeded 1.0 in 30% of women and 12% of men ≥50 years of age, values that are similar to the reported frequency of vertebral fracture. Conclusion: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT‐based biomechanical approach for assessment of fracture risk.

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