Unsolved Issues in Managing CKD-Associated Osteoporosis: Myths, Facts, and Clinical Grey Zones

Chronic kidney disease-mineral and bone disorder is a major contributor to skeletal fragility in patients with chronic kidney disease and after kidney transplantation. Alterations in mineral metabolism begin early during CKD and persist through later stages, leading to a markedly increased fracture risk that may precede renal failure. Bone fragility in CKD arises from the interplay of primary osteoporosis, secondary causes, and CKD-specific disturbances in bone turnover and mineralisation. CKD related bone disease and post-transplant bone loss are characterised not only by reduced bone mineral density but also by impaired bone quality, driven by abnormalities in trabecular and cortical microarchitecture, collagen properties, and mineral composition. Immunosuppressive therapy further exacerbates skeletal vulnerability after kidney transplantation. Recent guidelines have therefore adopted the term CKD-associated osteoporosis to emphasise the need for integrated diagnostic and therapeutic approaches. Diagnosis remains challenging because BMD alone fails to capture alterations in bone turnover and mineralisation that critically influence fracture risk and treatment response. Although bone biopsy remains the reference standard, limited availability has led to increased reliance on bone turnover markers, particularly those not cleared by the kidneys. Combined assessment of parathyroid hormone and BTMs improves discrimination of turnover states and supports individualised clinical decision-making. A pragmatic approach could be based on an integrated evaluation of CKD-MBD parameters, BTM trends, and baseline and follow-up imaging. Therapeutic management becomes increasingly complex in advanced CKD, where fracture risk is high, and evidence for osteoporosis treatments is limited. Antiresorptive, osteoanabolic, and dual-action agents have distinct effects on bone modelling and remodelling, with important implications for efficacy and safety. Despite progress, no consensus exists on optimal treatment strategies. Emerging sequential and combination therapies remain insufficiently studied in advanced CKD and transplant populations, underscoring the need for robust clinical evidence.