The Conundrum of Medical Fracture Prevention in Chronic Kidney Disease-Summary of the Evidence and Pragmatic Clinical Guidance.

Fragility fractures are a major complication in chronic kidney disease (CKD), yet therapeutic strategies for their prevention remain highly controversial. The unique pathophysiology of CKD-mineral and bone disorder (CKD-MBD), coupled with the paucity of dedicated clinical trials, create substantial uncertainty regarding the efficacy and safety of medical interventions established in the general osteoporosis population. This review summarizes the available evidence regarding fracture risk and bone mineral density including pragmatic clinical guidance for the use of calcium, vitamin D, phosphate binders, calcimimetics, bisphosphonates, denosumab, romosozumab, and teriparatide in patients with advanced non-dialysis CKD, on dialysis, and after kidney transplantation. For calcium, the conflicting balance between skeletal needs and risk of vascular calcification in the setting of declining kidney function and limited evidence for fracture prevention is outlined. For vitamin D, the gap between its widespread clinical use and the inconsistent data on fracture prevention is analyzed including a discussion of target levels in progressive kidney dysfunction. For phosphate binders, the evidence for fracture prevention, showing benefits in dialysis populations, is summarized together with a synthesis of data on potential risks of calcium-based agents. For calcimimetics, the available evidence on their role in fracture prevention, PTH, and calcium control is reviewed. For bisphosphonates, the unresolved question of benefit versus harm in advanced CKD stages are discussed and the evidence regarding efficacy and safety for various clinical settings is disentangled. For denosumab, the current data on fracture prevention is presented with emphasis on its renal-independent pharmacokinetics and strategies to mitigate hypocalcemia and rebound fracture risk. For romosozumab, the promising effects on bone health are reviewed alongside an analysis of cardiovascular safety data. For teriparatide, the limited evidence in patients with low bone turnover disease is evaluated. The review navigates the available evidence and unresolved controversies across therapeutic options, and provides pragmatic guidance to support individualized clinical decision-making.