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Long-Term Effect of Denosumab on Bone Disease in Patients with CKD
Ken Iseri1, Masahide Mizobuchi1, Renaud Winzenrieth2
1Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
Insights
Denosumab therapy increases hip bone mineral density (BMD) and strength in dialysis patients. Discontinuation leads to substantial BMD loss, particularly in cortical bone, highlighting the need for careful management of denosumab in this population.
Area of Science:
- Nephrology
- Orthopedics
- Radiology
Background:
- Long-term effects of denosumab on hip bone in dialysis patients are unknown.
- Dialysis patients are at high risk for bone disease.
Purpose of the Study:
- To evaluate the impact of denosumab therapy and discontinuation on hip bone compartments and strength in dialysis patients.
- To analyze changes in cortical and trabecular bone mineral density (BMD) and estimated strength indices.
Main Methods:
- Retrospective study of 124 dialysis patients using 3D-SHAPER software.
- Analysis of hip bone parameters before, during, and after denosumab therapy (up to 5 years).
- Statistical comparison using Wilcoxon signed-rank test.
Main Results:
- Denosumab therapy significantly increased areal BMD, cortical volumetric BMD, cortical surface BMD, and cortical thickness.
- Trabecular volumetric BMD and estimated strength indices also improved with denosumab.
- Discontinuation of denosumab led to significant worsening of these parameters, especially at the lateral greater trochanter.
Conclusions:
- Denosumab therapy enhances hip bone mineral density and strength in dialysis patients.
- Discontinuation of denosumab results in substantial bone loss, emphasizing the need for careful treatment strategies.
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.
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