The Interplay of Local and Systemic Factors in the Pathogenesis of Osteoporosis

摘要

In 1998, I summarized our knowledge of the pathogenesis of osteoporosis and suggested the potential importance of the interplay of local and systemic factors (1). This suggestion was based on the fact that the changes of the skeleton that led to decreased bone mass and increased fragility were not uniformly distributed, but had a predilection for certain sites and the fact that one could not clearly correlate the severity of osteoporosis with changes in circulating levels of systemic hormones. During the past 10 years, this suggestion has turned into an accepted concept. Local factors have been demonstrated to play a role in bone loss in animal models of osteoporosis. In addition, new concepts of the genetic determinants of osteoporosis and further insights into the role of systemic hormones have been achieved. The recent identification of the proteins which are critical for the interaction between cells of the osteoblastic lineage and osteoclast precursors that results in stimulation of bone resorption, as well as an inhibitor which blocks this interaction, has provided an exciting new approach to the question of local regulation (2,3). However, the specific local factors which might be most important in pathogenesis in human osteoporosis have still not been identified. In this review, I will summarize the most recent findings concrning the roles of systemic hormones, cytokines, prostaglandins, and growth factors in the pathogenesis of bone loss in humans and in animal models.