Vertebral fractures (VFX) are caused by low bone mass and microstructural deterioration of bone tissue. The latter is not well defined. We investigated bone structure in transiliac biopsy specimens from 88 volunteers. Biopsy specimens were obtained at baseline in the Multiple Outcomes of Raloxifene Evaluation trail, a prospective study in osteoporotic (BMD < or = -2.5 T score) postmenopausal women without or with VFX on standardized lateral spinal radiographs. Bone biopsy specimens were embedded in methylmethacrylate (MMA). Histomorphometry was done in 8 microns (U.S.A.) or 5 microns (Europe) Goldner stained sections. Vertebral fracture status (yes/no) was the outcome variable in logistic regression models adjusted for age and biopsy specimen origin (U.S.A. vs. Europe). Patients with and without VFX (26/62) were similar regarding age (69.2 +/- 5.2 years vs. 67.3 +/- 6.7 years), bone volume (BV/TV; 17.7 +/- 4.7% vs. 19.0 +/- 5.8%), and bone surface (BS/TV; 2.7 +/- 0.6 mm2/mm3 vs. 2.8 +/- 0.6 mm2/mm3). A lower cortical thickness (C.Th; 652 +/- 267 microns vs. 822 +/- 325 microns), total strut length (TSL; 826 +/- 226 microns/mm2 vs. 922 +/- 256 microns/mm2), node-to-loop (Nd-Lp) strut length (10.1 +/- 10.3% vs. 15.0 +/- 13.6%), together with a higher node-to-terminus (Nd-Tm) strut length (45.6 +/- 9.7% vs. 39.1 +/- 9.3%) were each associated with prevalent VFX (0.01 < p < 0.10). Differences in BV/TV did not explain these associations. In conclusion, cortical thinning and disruption of trabecular lattice are possible pathogenic mechanisms in patients with VFX.