Management of fracture risk in CKD—traditional and novel approaches

Abstract

The coexistence of osteoporosis and chronic kidney disease (CKD) is an evolving health care challenge in the face of increasingly aging populations. Globally, accelerating fracture incidence causes disability, impaired quality of life, and increased mortality. Consequently, several novel diagnostic and therapeutic tools have been introduced for treatment and prevention of fragility fractures. Despite an especially high fracture risk in CKD, these patients are commonly excluded from interventional trials and clinical guidelines. While management of fracture risk in CKD has been discussed in recent opinion-based reviews and consensus papers in the nephrology literature, many patients with CKD stages 3–5D and osteoporosis are still underdiagnosed and untreated. The current review addresses this potential treatment nihilism by discussing established and novel approaches to diagnosis and prevention of fracture risk in patients with CKD stages 3–5D. Skeletal disorders are common in CKD. A wide variety of underlying pathophysiological processes have been identified, including premature aging, chronic wasting, and disturbances in vitamin D and mineral metabolism, which may impact bone fragility beyond established osteoporosis. We discuss current and emerging concepts of CKD—mineral and bone disorders (CKD-MBD) and integrate management of osteoporosis in CKD with current recommendations for management of CKD-MBD. While many diagnostic and therapeutic approaches to osteoporosis can be applied to patients with CKD, some limitations and caveats need to be considered. Consequently, clinical trials are needed that specifically study fracture prevention strategies in patients with CKD stages 3–5D.

Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis

“…New guidelines suggest that BMD should also be assessed in CKD patients if results will impact clinical decisions (i.e., individualized prescription of anti-OP drugs). Several illustrative algorithms for CKD patients have already been published, broadly calling for a shift from nihilism to pragmatism ( Pimentel et al, 2017 ; Evenepoel et al, 2021b ; Evenepoel et al, 2021c ; Pimentel et al, 2021 ; Casado et al, 2022 ; Ginsberg and Ix, 2022 ; Haarhaus et al, 2022 ). However, it is still prudent to use these drugs (bisphosphonates, denosumab, recombinant PTH and romosozumab) with caution, especially in advanced kidney disease, balancing the risk/benefit ratio, since, as documented in this article, pathophysiological pathways are extremely intricate and not completely unraveled yet.…”

Bones of contention: Predicting and preventing fractures in patients receiving peritoneal dialysis

“…While there have been no dialysis-specific studies, literature in the general population supporting lifestyle and dietary interventions for osteoporosis are likely applicable to those receiving dialysis. 22…”

“…26 The improvements in fracture risk seen after cinacalcet and parathyroidectomy (both of which lower bone turnover) as well as the sustained improvement in BMD with prolonged denosumab use in the general population despite persistent low bone turnover have also called this theoretical risk into question. 22 The 2017 update of the KDIGO guidelines, in fact, removed the requirement for bone biopsy prior to starting antiresorptive therapy. 26 In our centre, we do still avoid antiresorptive therapy in those receiving dialysis with a low PTH (i.e.…”

“…While there have been no dialysisspecific studies, literature in the general population supporting lifestyle and dietary interventions for osteoporosis are likely applicable to those receiving dialysis. 22 In those with significant secondary or tertiary hyperparathyroidism, cinacalcet and parathyroidectomy are both associated with a decreased risk of fracture. The EVOLVE trial randomised 3883 patients receiving haemodialysis to cinacalcet or placebo and followed them for up to 5 years.…”

“…23 Similarly, observational evidence shows that parathyroidectomy lowers fracture risk and increases in BMD. 22,24 There is little evidence regarding strategies to improve CKD-MBD including phosphate control and activated vitamin D supplementation; existing studies are often limited by small sizes and low power. 25…”