Biological characteristics of osteoporosis drugs: the effect of osteoblast–osteoclast coupling

Osteoporosis is a common disease where bone mass is reduced, leading to an increased risk of bone fracture. Half of Caucasian women and a fifth of men experience osteoporosisrelated bone fracture in the course of lifetime [1]. Treatment of osteoporosis-related fracture causes enormous socioeconomic burden, costing nearly $17 billion in 2005 in the U.S.; it is expected to double or triple in the next four decades due to rapidly aging population [2]. Osteoporosis is caused by an imbalance of osteoblastic bone formation and osteoclastic bone resorption. Thus, antiosteoporosis medications aim to reduce the risk of bone fracture either by increasing bone formation or suppressing bone resorption. Currently, four classes of anti-resorptive agents and one class of anabolic agent are approved by the U.S. Food and Drug Administration for the treatment of osteoporosis (Table 1). However, these medications have failed to increase bone formation or decrease bone resorption in isolation due to the closed coupling of osteoblasts and osteoclasts whereby changes in differentiation or activity of one cell type directly affect the other [3]. This phenomenon not only limits the efficacy of anti-osteoporosis drugs, but also is associated with significant side effects [4]. In this article, we review the biological aspects of anti-osteoporosis drugs, focusing on the mechanisms of action and osteoblast–osteoclast coupling.