Novel Drugs and Their Stem Cell-based Targets for Osteoporosis: Challenges and Proceedings
Pp. 1-38 (38)
Basma El Khaldi-Hansen, Markus Witzler, Margit Schulze, Patrick F. Ottensmeyer, Juliana Baranova and Tobiasch Edda
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.
Antiresorptive, Bisphosphonates, Cathepsin K, Hematopoietic stem cells, Osteoporosis, Osteoanabolic, Regenerative medicine, Mesenchymal stem cells, X-ray.
Bonn-Rhine-Sieg University of Applied Sciences, Department of Natural Sciences, 53359 Rheinbach, Germany.