CXCR4 role in the anabolic response of teriparatide in bone

Osteoporosis is a common disease that alters the bone mass and quality and leads to an increased risk of fracture. It affects more than 200 million women worldwide causing more 9 million of fractures per year, with direct costs exceeding 56.9 billion euros only in Europe. In Austria, more than 550,000 individuals had osteoporosis in 2019, causing 110,000 new fragility fractures with direct costs to the health system of 1.3 billion euros. Teriparatide is an effective treatment to build new bone in patients presenting severe osteoporosis; however, the treatment is costly, and the response is variable. Many patients do not respond well to the treatment and continue losing bone with a large risk to develop a fragility fracture. We found that genetic markers are associated with the response to treatment, and we want to investigate how this is occurring. Our findings appointed to CXCR4 gene, located in the chromosome 2, as associated with response to teriparatide. In order to understand the role of CXCR4 in osteoporosis and how it could promote a good response to treatment, we will develop an animal model containing a deficient copy of CXCR4 and treat it with teriparatide. Then, we will check the bone tissue to find changes in mass and structure compared with those animals with a functional CXCR4 gene. We will also collect osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells, to identify molecular targets that could be associated with the bone changes. Our aim is to uncover targets that could be pharmacologically regulated in future in those patients who do not respond well to teriparatide, in order to improve their outcome. Thus, we could provide a personalised care for them. Besides, we also expect to identify targets involved in the development of osteoporosis, with the potential to develop novel drugs for its treatment.