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PhD candidate on the genetic background of atypical femur fractures
You will conduct research into the genetic background of atypical femur fractures (AFFs) associated with the use of antiresorptive drugs. These unusual fractures are a very rare but serious side effect of bisphosphonates and other inhibitors of bone resorption that are used to prevent fractures in patients with osteoporosis. Despite the fact that the chance of an AFF is very small, the fear of such a side effect, both among doctors and patients, has resulted in a large decline of about 50% in the use of these effective anti-fracture drugs, leading to under-treatment of patients with osteoporosis. It is likely that patients with AFF have a genetic predisposition with specific genetic variants and an altered gene expression profile. These variants may interact with non-genetic factors like use of certain medication and clinical characteristics.
We aim to unravel these characteristics with the ultimate objective to develop a cheap genetic test in order to predict the occurrence of AFFs and restore faith in the use of bisphosphonates. In our Bone Center, an expert center for rare and complex bone diseases, we see most patients from the Netherlands with an AFF. We also collaborate with international consortia to build a large cohort of AFF cases. In our lab, we use 'state of the art' genomic and proteomic analyses.