#2793 Improvement of bone mineral density in kidney transplant recipients: it is just denosumab?
Authors: Barbuto Simona , Vetrano Daniele , Speciale Serena , Aguanno Francesco , Comai Giorgia , La Manna Gaetano , Cianciolo Giuseppe 
Published: May 2024

Abstract

Background and Aims
Post-transplant bone disease is a common complication after a kidney transplant. Several factors, including pre-existing CKD-MBD, steroid, and CNI immunosuppressive treatment, contribute to this condition and increase the risk of bone loss and fractures. Among various therapeutic strategies, Denosumab, a human monoclonal antibody against RANK-L, can decrease the risk of fracture in Kidney Transplant Recipients (KTRs). The most reported side effects are episodes of hypocalcemia, which are associated with an increase in parathyroid hormone (PTH) levels. The FDA recommends treating these episodes with calcium supplements and cholecalciferol; another alternative is the use of receptor activators (VDRa). To our knowledge, there are only a few case reports in the literature analyzing the effect of combined treatment with VDRa and Denosumab. In this observational study, we evaluated changes in laboratory data and bone density (BMD) assessed by DXA in KTRs that received Denosumab with or without VDRa supplementation.

Method
This retrospective study evaluated 18 kidney transplant recipients who started Denosumab therapy after transplantation. The patients were divided into two groups: those who started or increased vitamin D receptor agonist therapy within the first 6 months before the second dose of Denosumab, and those who did not. We analyzed at baseline (T0) and after 1 year from first Denosumab administration (T1) creatinine, calcium, phosphate, PTH, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX), and 25-OH vitamin D and BMD at vertebral lumbar spine, femoral neck and total Hip. Furthermore, we evaluated Trabecular Bone Score (TBS). We performed ANOVA and Kruskal-Wallis for continuous variables based on distribution and Fisher's test for categorical variables. To assess the correlation between variables, we used linear regression and the Pearson correlation coefficient. Additionally, we conducted logistic regression to analyze the outcomes.

Results
A total of 18 patients were included in the study cohort. Of these, 66.7% were females, and 33.3% were males, with an average age of 67 years (Table 1). 13 patients started or uptitrated VDRa within the first 6 months (VDRa group), while 5 did not (Control group). At baseline, the VDRa group had a lower eGFR and higher PTH compared to the Control group, although both were at the threshold of statistical significance (37.38 vs 52.20 mL/min/1.73 m², p = 0.060 and 106.77 vs 72.60 pg/mL, p = 0.069). However, they had significantly lower serum calcium levels (8.96 vs 9.90 mg/dL, p = 0.039). In terms of baseline bone structure, there were no significant differences between the two groups at any of the three sites examined. At 1 year the VDRa group had a significantly greater gain at the Total Hip (+0.08 vs −0.03 g/cm3, p = 0.048 and +10.81 vs −4.16%, p = 0.037). Additionally, the VDRa group had an increase in TBS, while the Control group had a reduction, and this absolute and percentage variation between the two was statistically significant (+0.07 vs −0.02, p = 0.034 and +6.14 vs −1.62, p = 0.043) (Table 2). In linear correlation analysis higher doses of VDRa were significantly and positively associated with Delta BMD at the Total Hip (r = 0.65, p = 0.003). However, a significant correlation was highlighted between VDRa dosage and PTH reduction (r = −0.51, p = 0.027). Finally, in univariate logistic regression analysis, the dosage of VDRA was significantly and positively associated with 5% BMD gain at the Total Hip (OR = 1.54, CI 1.08 to 1.89, p = 0.046) (Fig. 1).

Conclusion
After conducting our study, we found that the use of Denosumab had a positive impact on bone mineral density. In addition to that, we observed that the association with VDRa led to further improvement in BMD and better control of PTH. Despite having a small sample size, our study demonstrates that VDRa not only helps in correcting hypocalcemia but also enhances the effect of Denosumab.