Novel Drugs and Their Stem Cell-based Targets for Osteoporosis: Challenges and Proceedings

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The aging of the population goes along with age-related diseases, such asosteoporosis, a disorder of bone remodeling. Bone homeostasis is maintained by bonebuildingosteoblasts and bone-resorbing osteoclasts. During osteoporosis, this balanceis disturbed by augmented bone resorption, which leads to an increased risk of bonefractures, with potentially lethal consequences. To battle this, various drugs withdifferent target sites are used. Currently, the gold standard osteoporosis medications arethe bisphosphonates, which induce apoptosis of the osteoclasts. However,bisphosphonates may cause adverse effects, such as osteonecrosis of the jawbone.Other available drugs for bone metabolism disorders also exhibit undesired side- andoff-target effects of varying severity. Thus, new potential drug candidates are beingdeveloped, some already reached phase II or phase III clinical trials. The modes ofaction of these drug candidates range from anti-resorptive to osteoanabolic therapies.Osteoanabolic therapies stimulate the formation of bone, while anti-resorptive therapiesdecrease the bone resorption. Most anti-resorptive therapies induce apoptosis of theosteoclasts, which negatively affects the osteoblasts as well since there is a feedbackloop between these two cell types. A better understanding of bone homeostasis,beginning with the differentiation pathways of mesenchymal stem cells towardsosteoblasts and hematopoietic stem cells towards osteoclasts and their interactionsduring these differentiation processes are of increasing interest for future osteoporosistreatments with minimal side effects. This chapter focuses on the differentiation andsignaling pathways of osteoblasts and osteoclasts. In addition, new osteoporosis drugsare illuminated from the biological and the chemical point of view. Their progress frombench to bedside is presented.