Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Room 312
Background: Kidney transplantation is associated with bone loss and an increased risk of fracture. Since current therapeutic options to prevent bone loss are limited we assessed the efficacy and safety of Receptor Activator of Nuclear Factor κB Ligand (RANKL) inhibition with denosumab to improve bone mineralization in the first year after kidney transplantation (NCT01377467).
Methods: We enrolled 108 kidney transplant recipients and randomized 90 patients two weeks after surgery in a 1:1 ratio to receive denosumab (subcutaneous injections of 60 mg denosumab at baseline and after 6 months) or no treatment. The primary endpoint was percentage change in bone mineral density (BMD) measured by DXA at the lumbar spine at 12 months.
Results: After 12 months, the primary outcome of total lumbar spine BMD increased by 4.6% (95% CI 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8-0.9%) in 44 patients in the control group (between-group difference 5.1%, 95% CI 3.1-7.0%, p<0.0001). Denosumab also significantly increased BMD at the total hip by 1.9% (95% CI, 0.1 to 3.7%; p=0.035) over that in the control group at 12 months. Biomarkers of bone resorption (β-CTX, urine deoxpyridinoline) and bone formation (P1NP, BSAP) markedly decreased with denosumab (p<0.001), whereas 25 (OH) and 1,25 (OH)2 vitamin D3 were not changed by denosumab. Interestingly there was a delayed decrease of PTH, a higher incidence of asymptomatic and transient hypocalcemia (≤1.9 mmol/l) (12 vs 1 episodes) but a lower incidence of hypercalcemia (>2.6 mmol/l) (37 vs 55 episodes) with denosumab. A 3-year safety follow-up showed excellent graft function (eGFR 59.7 vs 58.0 ml/min/1.73 m2) and a similar improvement of the persistent hyperparathyroidism in both groups.
Conclusions: Antagonizing RANKL with denosumab effectively increased BMD in de novo kidney transplant recipients, improved hypercalcemia but caused more frequent episodes of asymptomatic hypocalcemia. Denosumab appears therefore to be suitable to improve bone health after kidney transplantation.
CITATION INFORMATION: Bonani M, Frey D, Brockmann J, Fehr T, Müller T, Graf N, Wüthrich R. Denosumab Prevents Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: Results from a Randomized Controlled Trial. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Bonani M, Frey D, Brockmann J, Fehr T, Müller T, Graf N, Wüthrich R. Denosumab Prevents Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: Results from a Randomized Controlled Trial. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/denosumab-prevents-bone-mineral-density-loss-in-de-novo-kidney-transplant-recipients-results-from-a-randomized-controlled-trial/. Accessed June 26, 2019.
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