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

The aging of the population goes along with age-related diseases, such as osteoporosis, a disorder of bone remodeling. Bone homeostasis is maintained by bonebuilding osteoblasts and bone-resorbing osteoclasts. During osteoporosis, this balance is disturbed by augmented bone resorption, which leads to an increased risk of bone fractures, with potentially lethal consequences. To battle this, various drugs with different target sites are used. Currently, the gold standard osteoporosis medications are the 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- and off-target effects of varying severity. Thus, new potential drug candidates are being developed, some already reached phase II or phase III clinical trials. The modes of action of these drug candidates range from anti-resorptive to osteoanabolic therapies. Osteoanabolic therapies stimulate the formation of bone, while anti-resorptive therapies decrease the bone resorption. Most anti-resorptive therapies induce apoptosis of the osteoclasts, which negatively affects the osteoblasts as well since there is a feedback loop between these two cell types. A better understanding of bone homeostasis, beginning with the differentiation pathways of mesenchymal stem cells towards osteoblasts and hematopoietic stem cells towards osteoclasts and their interactions during these differentiation processes are of increasing interest for future osteoporosis treatments with minimal side effects. This chapter focuses on the differentiation and signaling pathways of osteoblasts and osteoclasts. In addition, new osteoporosis drugs are illuminated from the biological and the chemical point of view. Their progress from bench to bedside is presented.