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 trial, a prospective study in osteoporotic (BMD less than or equal to -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 mu m (U.S.A.) or 5 mu m (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 mm(2)/mm(3) vs. 2.8 +/- 0.6 mm(2)/mm(3)). A lower cortical thickness (C.Th; 652 +/- 267 mu m vs. 822 +/- 325 mu m), total strut length (TSL; 826 +/- 226 mu m/mm(2) vs. 922 +/- 256 mu m/mm(2)), 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.