Adynamic Bone Disease in Chronic Kidney Disease: From PTH Suppression-Driven Remodeling Phenotype to Osteoanabolic...

Adynamic bone disease (ABD) is an increasingly prevalent form of low-turnover renal osteodystrophy in advanced chronic kidney disease (CKD). ABD was not recognized as a clinical entity prior to the widespread adoption of PTH-targeted therapeutic strategies, and sustained iatrogenic suppression of parathyroid hormone (PTH) activity is now understood as the primary and defining causal mechanism underlying the adynamic phenotype. Uremic toxins, FGF-23-Klotho dysregulation, impaired vitamin D signaling, chronic inflammation, calcium-phosphate imbalance, and osteocyte-mediated abnormalities function as modulatory contributors that amplify skeletal susceptibility within the context of sustained PTH suppression, rather than independent drivers of ABD. Clinically, ABD is associated with impaired bone quality, increased fracture risk, vascular calcification, and musculoskeletal frailty, abnormalities that are often not adequately reflected by areal bone mineral density measurements alone.

ABD in advanced CKD represents a PTH suppression-driven skeletal remodeling phenotype characterized by osteoblast, osteoclast, and osteocyte dysfunction together with disruption of osteoblast-osteoclast coupling. Suppression of Wnt/β-catenin signaling, elevated sclerostin expression, impaired mechanotransduction, skeletal resistance to PTH, and accumulation of uremic toxins collectively contribute to globally reduced remodeling activity and defective microdamage repair. In the context of markedly suppressed bone turnover, antiresorptive therapy is biologically unlikely to confer skeletal benefit and may exacerbate impairment of bone remodeling and renewal. By contrast, anabolic strategies aimed at restoring PTH1R-dependent bone formation and remodeling activation are mechanistically appropriate in CKD-associated ABD. Current evidence suggests that intermittent PTH analog therapy, particularly teriparatide, may improve bone formation markers, bone mineral density, and remodeling activity in selected CKD patients with low-turnover bone disease. Abaloparatide is mechanistically promising but clinically unvalidated in advanced CKD. Romosozumab should not be used in clinical practice for CKD-associated ABD given profound uncertainties regarding cardiovascular safety, vascular calcification, and calcium handling in this population. Practical considerations regarding patient selection, biochemical monitoring, prevention of ABD through avoidance of prolonged PTH suppression, and individualized treatment strategies are also discussed.