#2903 Effect of denosumab on bone mineral density and microarchitecture assessed by HRpQCT in dialysis patients: a longitudinal study

Abstract Background and Aims Dialysis patients have higher risk of fragility fracture. Denosumab (Dmab) had been shown to increase bone mineral density (BMD) in short term open trials. The effect of Dmab on trabecular and cortical bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) in dialysis patients has not been reported over a long-term period. Method 32 consecutive dialysis patients managed at a single center between 2014 and 2024 and having performed at least one HRpQCT were included. Patients with recent fractures and BMD lower than −2.5 SD at the total hip were treated with Dmab 60 mg every 6 months. The study protocol included a HRpQCT at the right distal tibia and radius at baseline and every year, and a dual-energy X-ray absorptiometry (DXA) at the lumbar spine, total hip, femoral neck, one-third and ultradistal radius at baseline and annually during the follow-up. HRpQCT data were not analyzed if performed (i) one year after a kidney transplantation or a parathyroidectomy and (ii) in the Dmab group, 6 months after the last administration in cases of treatment withdrawal. We applied linear mixed models for repeated measures (MMRMs) to assess the effect of Dmab on (i) HRpQCT parameters studied: ratio of bone volume to total volume (BV/TV), trabecular volumetric mineral density (Dtrab), cortical volumetric mineral density (Dcomp), cortical thickness (CtTh), and cortical perimeter (CtPm) and (ii) bone mineral density (BMD) obtained by DXA at each measurement site. Results During a median [interquartile range (IQR)] follow-up period of 1.8 [1.2–2.5] years, 19 dialysis patients had repeated HRpQCT over time, including nine patients treated with Dmab. The median [IQR] age of the whole population was 68.9 [62.1–76.6] years, 23 (71.9%) were female (including 21 menopausal women). The only baseline characteristic significantly associated with the use of Dmab was a previous fracture (92.9% in the Dmab group vs 50% in the no-Dmab group, P = 0.027). The mean (standard deviation (SD)) trabecular BV/TV changes between baseline and the last HRpQCT measurement (regardless of the time between the two HRpQCTs) was a gain of +2.2% ± 4.5% in the Dmab group vs a loss of −15.9% ± 11.7% in the no-Dmab group at the distal tibia, and a gain of +3.5% ± 7.4% in the Dmab group vs a loss of −14.8% ± 12.4% in the no-Dmab group at the distal radius. These Tb BV/TV changes in the Dmab group (vs no-Dmab group) were significant in MMRM analyses at the distal tibia (P = 0.006), and at the distal radius (P = 0.002). The mean (SD) Dtrab changes was +2.2% ± 4.5% in the Dmab group vs −15.9% ± 11.7% in the no-Dmab group at the distal tibia, and +3.3% ± 7.7% in the Dmab group vs −14.6% ± 12.6% in the no-Dmab group at the distal radius. The Dtrab changes in the Dmab group vs no-Dmab group were significant in MMRM analyses at the distal tibia (P = 0.006), and at the distal radius (P = 0.002). Changes over time in cortical parameters (Dcomp, CtTh and CtPm) were not statistically significant between groups in MMRM analyses. The mean (SD) BMD changes between the first and the last DXA (regardless of the time between the two DXA) at the lumbar spine, total hip, femoral neck, one-third and ultradistal radius were +9.3% ± 11.5%, +4.9% ± 6.2%, +13.6% ± 17.9%, +7.2% ± 12.4% and +6.4% ± 8.8% in the Dmab group, respectively, and −4.0% ± 11.8%, −8.5% ± 9.4%, −10.2% ± 4.6%, +0.9% ± 3.4% and −4.5% ± 13.1% in the no-Dmab group, respectively. These changes between groups were significant at total hip site in MMRM analyses (P = 0.008). Conclusion Dmab treatment improves trabecular bone volume parameters over time in dialysis patients with low BMD, thus preventing the persistent and progressive trabecular bone loss observed in the absence of treatment.