Pathogenesis of the Osteoporoses

Abstract

Although some densitometric diagnostic criteria for postmenopausal osteopenia and osteoporosis have become available, an understanding of the underlying contributors to bone fragility and of the processes by which the osteoporoses occur can be helpful in understanding and selecting appropriate diagnostic and therapeutic approaches. Enhanced bone fragility, the hallmark of all osteoporoses, may be considered the result of diminished bone quality. The classic triad of bone quality is bone volume, bone material properties, and bone architecture. Although these are inevitably interlinked in actual practice, it is appropriate to assess each in turn, because some pathogenic processes and therapeutic approaches may affect these components differently. For example, an approach that uses bone mineral density as the sole assessment of an antiresorptive agent's efficacy might confuse changes in material properties, e.g., increased secondary mineralization, with increases in bone volume, per se. Furthermore, densitometric changes will not reflect the architectural protection gained by such agents. Viewing the process of osteoporosis through the dynamics of remodeling allows an understanding of how disordered resorption and formation lead to alterations in bone quality. The common pathways of enhanced resorption and diminished formation lead directly to loss of volume and decay in architecture. New data on heterogeneity in regulatory and structural genes now suggest direct effects on bone material properties in collagen structure and mineralization. The systemic and local factors that modulate these remodeling activities continue to be elucidated. As we learn the direct effects of these factors on the recruitment, maturation, and function of the cells within the remodeling unit, and as cross-talk among them is better understood, better targeted diagnostics and therapeutic targets will be possible. Current diagnostics and therapeutics may focus prematurely on only selective aspects of bone quality. Future work should include a better understanding of bone quality, its expression through diagnostics, and its optimization through therapeutics.