Grant: Project Grant

It is now well recognized that people with chronic kidney disease (CKD) have weak bones. However, in contrast to people with osteoporosis, those with CKD have specific types of bone disease that could contraindicate the use of common anti-osteoporotic therapy. Indeed, up to 50% of people with CKD have what we call low bone turnover (LBT) disease (extremely low bone formation and resorption), in which anti-resorptive therapy is not recommended. In those patients, anabolic therapy (to stimulate bone formation) could be given. Identifying LBT disease is therefore of extreme importance if we want to propose adequate bone therapy in CKD patients. Until today, doing a bone biopsy at the iliac crest (anterior part of the hip) remains the only way to diagnose low bone turnover in CKD but is rarely done. Based on our prior works, we hypothesize that non-invasive markers could be used to identify CKD patients with LBT. Our global objective is to identify non-invasive biomarkers that will help in identifying patients with low vs non-LBT so that adequate anti-fracture therapy coud be offered. Methods We will recruit patients with CKD for iliac crest biopsy. We will compare CKD patients with low vs non-LBT. We will evaluate non-invasive biomarkers in the skin (AGEs) and in blood (AGEs, sclerostin, micro-ARNs) that may differentiate CKD patients with low vs non-LBT. Their predictive capacity will be evaluated alone or in combination. Then, Iliac crest biopsy specimens will be evaluated for bone quality parameters (microarchitecture, bone material composition) to evaluate the effects of LBT on bone strength. Significance Bone fragility is a major health issue in patients with CKD. We have a unique opportunity to conduct a bone biopsy study in this population to identify non-invasive markers that may predict LBT disease. Our results have the potential to change clinical practice so that personnalized bone therapy could be offered to CKD population.