To test the hypothesis that the association between bone mineral density (BMD) and estimated volumetric BMD and prevalent vertebral fractures differs in men and women, we studied 317 Caucasian men and 2,067 Caucasian women (average age 73 years). A total of 43 (14%) men and 386 (19%) women had a vertebral fracture identified on lateral spine radiographs using vertebral morphometry. Hip and spine areal BMD was about 1/3 standard deviation lower among men and women with a vertebral fracture. A 0.10 g/cm(2) decrease in areal BMD was associated with 30-40% increased odds of having a fracture in men and 60-70% increased likelihood in women. Low bone mineral apparent density (BMAD) was also associated with 40-50% increased odds of a vertebral fracture in both genders. The probability of a man having a fracture was observed at higher absolute areal BMD values than observed for women (P=values for interaction of BMD x gender: trochanter, P=0.05; femoral neck, P=0.10; total hip, P=0.09). In contrast, the probability of fracture was similar in men and women across the range of estimated volumetric BMD (BMAD). In conclusion, low BMD and low BMAD are associated with increased odds of vertebral fracture in both men and women. Measures of bone mass that partially correct for gender differences in bone size may yield universal estimates of fracture risk. Prospective studies are needed to confirm this observation.