Osteoporosis is a disease defined by decreased bone mass and alteration of microarchitecture which results in increased bone fragility and increased risk of fracture. The major complication of osteoporosis, i.e., fracture, is due to a lower bone strength. Thus, any treatment of osteoporosis implies an improvement in bone strength. Bone strength is determined by bone geometry, cortical thickness and porosity, trabecular bone morphology, and intrinsic properties of bony tissue. Bone strength is indirectly estimated by bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). Since DXA-measured BMD accounts for 60–70% of the variation in bone strength, some important factors are not captured by DXA in the progression of osteoporosis and the effects of antiosteoporotic treatment. Geometry and trabecular microarchitecture have also to be taken into account. Thus, the assessment of intrinsic mechanical quality of bony tissue should provide a better understanding of the role of tissue quality in determining bone strength. The careful investigation of all the determinants of bone strength (bone tissue included) should be considered in the pathophysiology of osteoporosis and in the mechanisms of action of antiosteoporotic drugs.