Long-Term Effect of Denosumab on Bone Disease in Patients with CKD

Abstract

Background The effect of long-term denosumab therapy and of denosumab discontinuation on the cortical bone of the hip regions in dialysis patients has not been studied. Methods This retrospective study investigated the cortical and trabecular compartments and estimated strength indices of the hip region, obtained using 3D-SHAPER software, after a maximum of 5 years of denosumab therapy in 124 dialysis patients. A Wilcoxon signed-rank test was used to identify the differences in each parameter before and after denosumab initiation. Similarly, we investigated the changes in these parameters after denosumab discontinuation in 11 dialysis patients. Results Integral and trabecular volumetric bone mineral densities (BMD) were significantly lower at the start of denosumab therapy than those in 1 year before denosumab initiation. After starting denosumab, areal BMD (median change +7.7% (interquartile range [IQR], +4.6 to +10.6), cortical volumetric BMD (median change +3.4% [IQR, +1.0 to +4.7]), cortical surface BMD (median change +7.1% [IQR, +3.4 to +9.4]), and cortical thickness (median change +3.2% [IQR, +1.8 to +4.9]) showed a significantly higher trend for 3.5 years, which then stabilized at a higher value compared with baseline. A similar trend in the trabecular volumetric BMD (median change +9.8% [IQR, +3.8 to +15.7]) was observed over 2.5 years, with a higher value maintained thereafter. The whole area of the hip region improved after denosumab therapy. Similar trajectories were also found in the estimated strength indices. Conversely, at 1 year after denosumab discontinuation, these 3D parameters and estimated strength indices tended to largely worsen. The lateral aspect of the greater trochanter was the most pronounced location showing volumetric BMD loss. Conclusions The BMD of both cortical and trabecular components in the hip region was significantly higher after starting denosumab therapy. However, these measurements exhibited a trend of declining substantially after the discontinuation of denosumab.

Treating Osteoporosis with Denosumab in Patients on Hemodialysis

“…3D imaging analyses imply that denosumab is an important agent to heal cortical bone defects in kidney failure—making it a powerful tool to prevent fractures in a very high-risk population. 3 However, efficacy and safety data are lacking. Clinical trial data demonstrating antifracture efficacy in CKD populations will require thousands of patients and take many years to complete.…”

“…In this issue of CJASN , Iseri et al provide valuable insight into mechanistic effects of denosumab on skeletal structure in patients with kidney failure on hemodialysis. 3 This observational study in 124 patients used 3D-SHAPER software, a novel tool that constructs 3D images of the total hip on the basis of DXA datasets. The method provides compartmental analyses of femoral structure, including cortical and trabecular volumetric bone mineral density (BMD), and cortical thickness and surface BMD.…”

Effect of denosumab on the incidence of fractures and mortality in patients undergoing hemodialysis: A retrospective cohort study

“…7 Several studies have investigated the effects of denosumab in patients undergoing hemodialysis. [8][9][10][11][12] However, these studies included few participants and had short observational periods. Furthermore, no study has investigated the relationship between bone fractures and denosumab use in patients undergoing hemodialysis.…”

Managing Osteoporosis in Dialysis—A Medical Catch-22

“…In contrast to bisphosphonates, denosumab is not cleared by the kidney, thus mitigating fears of oversuppressing bone turnover due to drug accumulation in patients with poor kidney function. Although antifracture efficacy data in dialysis patients are lacking, small clinical trials have shown that denosumab increases bone mineral density in dialysis . As its use in dialysis patients has increased, safety concerns with denosumab have emerged, in particular the risk of hypocalcemia.…”

“…While turnover is one aspect of this, other critical facets of bone quality will not be fixed by parathyroid hormone suppression alone, such as the severe cortical and trabecular microarchitectural impairments that develop in CKD. Recent data using 3-dimensional imaging tools in dialysis patients suggest that denosumab improves cortical geometric features that highly relate to bone strength, thus possibly decreasing fracture risk …”