In clinical practice, the quantitative evaluation of bone tissue relies on dual-energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) values, which are closely associated with the risk of osteoporotic fracture. However, only a small fraction of the antifracture effect of bone resorption inhibitors is ascribable to BMD gains (4% with raloxifene and 16-28% with alendronate and risedronate). Bone quality encompasses a number of bone tissue properties that govern mechanical resistance, such as bone geometry, cortical properties, trabecular microarchitecture, bone tissue mineralization, quality of collagen and bone apatite crystal, and presence of microcracks. All these properties are dependent on bone turnover and its variations. In populations, the decreases in bone resorption markers achieved with resorption inhibitors may predict in part the decrease in fracture risk. At the spine, however, this correlation exists down to a 40% fall in bone resorption markers; larger drops did not provide further protection against fractures in patients taking risedronate in one evaluation of this relationship.

Osteoporosis medications can exert favorable effects on bone size and cortical thickness. Such effects have been documented with teriparatide (PTH 1-34), which is the unique purely anabolic treatment for osteoporosis available to date. More surprising are the favorable effects on bone size seen with some of the bone resorption inhibitors such as neridronate in adults with osteogenesis imperfecta. Similarly, estrogens and alendronate can increase femoral neck size in postmenopausal women. Preservation of the trabecular microarchitecture was demonstrated first with risedronate and subsequently with alendronate. In placebo-controlled studies, a deterioration in trabecular microarchitecture occurred within 1 to 3years in the placebo groups but not in the bisphosphonate groups. Teriparatide, in contrast, improves trabecular microarchitecture, in particular by increasing connectivity and improving the plate-rod distribution.

The minerals within trabecular or cortical bone can be evaluated using microradiography or synchrotron micro-computed tomography. Marked or prolonged secondary mineralization may result in poor bone quality. Increased bone mineralization is among the key effects of bone resorption inhibitors, most notably bisphosphonates. Prolonged use of the most potent bisphosphonates may lead to unwanted effects related to excessive mineralization. Microcracks may play a physiological role; however, a large number of microcracks may be deleterious via an effect on osteocytes. Excessive mineralization may promote the development of multiple microcracks. Studies of bone crystal and collagen properties with several bone resorption inhibitors, including risedronate and raloxifene, showed no harmful effects.

An increasing number (several hundreds) of mandibular osteonecrosis associated with bisphosphonate therapy has been reported. The typical patient was receiving injectable bisphosphonate therapy for bone cancer and had undergone dental work shortly before bisphosphonate administration. The mechanism of this adverse effect is poorly understood.