The pathophysiology of chronic kidney disease (CKD)-related mineral and bone disorder (CKD-MBD) extends far beyond simple mineral imbalances. Evolving from the traditional understanding of secondary hyperparathyroidism, the conceptual framework has recently been updated to recognize two distinct but overlapping clinical syndromes: CKD-associated osteoporosis, which encompasses the significantly increased fracture risk and microarchitectural deterioration in this population, and CKD-associated cardiovascular disease, which accounts for vascular and structural cardiac abnormalities, including medial vascular calcification. Unlike traditional osteoporosis, the two clinical syndromes emerge from intricate interactions between declining kidney function and dysregulated mineral metabolism. The early rise in fibroblast growth factor-23 levels, progressive phosphate retention, diminished vitamin D activation, secondary hyperparathyroidism, and uremic toxin accumulation, particularly uric acid and indoxyl sulfate, orchestrate profound disruptions in osteocyte, osteoblast and osteoclast function. The complex interaction amplifies in the dialysis population, where protein-energy wasting affects most patients, and intensifies following kidney transplantation owing to glucocorticoid, immunosuppressive, and anticoagulant treatments. Consequently, fracture rates in patients with CKD exceed those of age-matched controls by more than fourfold, with patients on dialysis therapy facing an up to eightfold increased risk. Available diagnostic and predictive tools need to be improved to adequately identify at-risk patients. The usefulness of additional, more recent biomarkers such as FGF-23, α-Klotho, and various bone turnover parameters remains a matter of debate. Bone biopsy, considered as the diagnostic gold-standard, remains impractical in routine practice. Dual-energy X-ray absorptiometry cannot provide information on the type of renal osteodystrophy. Moreover, it demonstrates limitations in the presence of severe vascular calcifications. Trabecular bone scores emerge as potential progress in non-invasive bone imaging, showing modest superiority over traditional densitometry in predicting fracture risks among secondary osteoporosis populations, yet large clinical trials with long-term follow-up are required. Therapeutic management spans from parathyroidectomy to pharmacological interventions with bisphosphonates, denosumab, teriparatide, romosozumab, whereas agents such as burosumab remain investigational, with no published clinical trials in this population. However, therapeutic nihilism persists, with most high-risk patients not receiving bone-targeted therapy despite accumulating safety data. Transforming care demands abandoning therapeutic nihilism, embracing personalized risk stratification, and conducting trials in populations historically excluded from bone health research.
Kanbay et al. (Mon,) studied this question.