Follow-Up of Bone Mineral Density Changes in de novo Kidney Transplant Recipients Treated with Two Doses of the Receptor Activator of Nuclear Factor κB Ligand Inhibitor Denosumab

• Published in: Kidney & blood pressure research Vol. 44; no. 5; pp. 1285 - 1293
• Main Authors: Kobel, Claudia, Frey, Diana, Graf, Nicole, Wüthrich, Rudolf P., Bonani, Marco
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.10.2019; Karger Publishers
• Subjects: Biomedical materials; Bone density; Bone Density - drug effects; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone mineral density; Bone turnover; Calcium; denosumab; Denosumab - pharmacology; Denosumab - therapeutic use; Dual energy X-ray absorptiometry; Female; Follow-Up Studies; Fractures; Hemodialysis; Hip; Humans; Immunotherapy; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney Transplantation - methods; Kidney transplants; Kidneys; Ligands; Male; Mann-Whitney U test; Menopause; Middle Aged; Monoclonal antibodies; Osteoporosis; Post-menopause; Regression analysis; Research Article; Spine; Spine (lumbar); Surgical implants; Transplantation; Vertebrae; Vitamin D; Osteoporosis; Bone mineral density; Denosumab; Kidney transplantation
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000503066

Abstract Background: Studies in women with post-menopausal osteoporosis have shown that discontinuation of treatment with denosumab leads to an increased risk of vertebral fractures because of rebound bone turnover and rapid loss of bone mineral density (BMD). Methods: In a post hoc analysis of the Prolia for Osteoporosis of Transplant Operated Patient study, we analyzed the effect of denosumab withdrawal on BMD changes. Twenty-five de novo kidney transplant recipients (KTR) who were treated for 1 year with 2 six-monthly doses of denosumab on top of standard treatment (daily calcium and vitamin D) were compared to a control group of 29 KTR who received standard treatment alone. BMD changes were analyzed by repeated dual-energy X-ray absorptiometry shortly after transplantation (baseline), after 6 and 12 months (active treatment phase) and after 2–6.5 years (follow-up phase). Results: The average BMD at the lumbar spine declined markedly after discontinuation of treatment with denosumab but increased again thereafter. Thus, the average monthly change in lumbar spine BMD from month 12 onward was only 0.1 ± 2.8‰ in the denosumab group but 1.5 ± 1.9‰ in the control group (p = 0.021). The average monthly change in lumbar spine BMD from baseline to follow-up was similar in the control and denosumab group (1.1 ± 1.2‰ vs. 1.5 ± 2.4‰, p = 0.788). Similar results were seen at the total hip. Conclusions: In de novo KTR treated with 2 doses of denosumab, we detect a marked decrease in lumbar spine and hip BMD when denosumab is discontinued. Denosumab treatment should therefore not be discontinued without considering an alternative antiresorptive treatment.