Reconsidering the effects of antiresorptive therapies in reducing osteoporotic fracture.

Concepts of what constitutes osteoporosis have evolved from the single criterion of low bone mass to a more inclusive consideration of bone strength, based on both quantity and quality. The evidence driving this shift is drawn from many sources. For example, recent studies of bone geometry have shown what engineers have always known: material properties and structural strength are inseparable. Genetic factors also argue against a one-dimensional (ID) view of osteoporosis. Large-scale family studies present a strong case for genetic influences on bone mass and predisposition to fracture. The contribution of aging to fracture risk has long been known, but we are only now beginning to understand what happens to bone remodeling and microstructure in an aging skeleton. The recognition that osteoporosis is far more complex than previously thought suggests that factors in addition to bone mineral density (BMD) may be useful for evaluating bone fragility and therapeutic effectiveness. Although assessment of BMD is noninvasive and widely available, the degree of increase in BMD alone fails to account for the broader effectiveness of antiresorptive agents in reducing the risk of fractures related to osteoporosis. Indeed, the very multiplicity of factors that determine fracture risk implies that response to therapy may be equally complex. Studies of response to antiresorptive agents and the cellular processes they induce are at best preliminary at this time. Although new technologies have been applied to studying bone microarchitecture, their invasive nature limits wide use. New methods are needed to provide insight into the causes and effects of bone fragility. The definition of osteoporosis, meanwhile, must still be considered a work in progress.