Osteoporosis is defined as a disease characterized by low bone mass and microarchitectural deterioration of trabecular bone leading to enhanced bone fragility. Various histomorphometric methods have been described to measure bone architecture on histological sections. However, not all of the methods are strictly equivalent and some of them appear able to detect differences earlier in the course of the disease. We have compared 8 histomorphometric methods known to characterize the architecture of trabecular bone in 154 male osteoporotic patients. Measurements were done on transiliac bone biopsies: Trabecular number, thickness, and separation (Tb.N, Tb.Th, Tb.Sp); Trabecular Bone Pattern Factor (TBPf); Euler-Poincaré's number (E); Interconnectivity Index (ICI); strut analysis of the trabecular network with the ratio of nodes/free-end (N/F); star volume of the bone marrow (V*m.space) and trabeculae (V*Tb) and the Kolmogorov fractal dimension of the trabecular boundaries (D). Relationships between the various architectural parameters were studied by hierarchical cluster analysis. Linear, hyperbolic, and exponential correlations were found between trabecular bone volume (BV/TV) and architectural parameters. Cluster analysis demonstrates the link between these architectural parameters. ICI, E, and TBPf, which reflect the amount of open/closed marrow cavities clustered together and appeared related to Tb.Sp, V*m.space which are indicators of the mean size of marrow cavities. Tb.Th, V*Tb and N/F flocked together as they reflect the trabecular size. Tb.N and D segregated together and seemed to best describe the trabecular network complexity. These histomorphometric techniques are correlated but correlations may be linear or nonlinear. Several histomorphometric techniques need to be used in parallel to appreciate the pathophysiological mechanisms of osteoporotic states. Microsc. Res. Tech. 45:303–312, 1999. © 1999 Wiley-Liss, Inc.