Abstract:
Osteoporosis therapies affect bone remodeling, maintain or increase bone mass and decrease fracture risk, either through anti-catabolic or through anabolic effects. Due to the coupling of resorption and formation, the changes in resorption or formation in response to the above therapies are usually in the same direction, resulting in initial increments in bone mass that ultimately plateau. The development of bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH) and strontium have stemmed from astute observations on their beneficial effect on bone. Conversely, mouse genetics studies have unraveled the genetic basis of rare inherited skeletal syndromes. These investigations have shed light on key genes and pathways regulating osteoclast and osteoblast formation, differentiation and function and simultaneously paved the way for new drug development. Two prominent signaling pathways, the receptor activator of the nuclear factor kappa B (RANK)-RANK ligand (RANKL) pathway and the Wnt canonical signaling pathway, are important targets for drug development through the use of ligands specific to RANKL or to the Wnt-lipoprotein receptor related protein (LRP) 5-6-frizzeled (Fzd) receptor complex (Wnt-LRP5-6-Fzd). This chapter reviews strontium, SERMs, selective androgen receptor modulators (SARMs) and other new therapies on the horizon. © 2010 Elsevier Inc. All rights reserved.