title: Effect of Twice-Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial.
abstract: We conducted an open-label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8% to 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 increased aBMD at the total hip by 1.9% (95% CI, 0.1-3.7%; p = 0.035) over that in the control group at 12 months. High-resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection.
authors.affiliation: Division of Nephrology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Bonani
authors.affiliation: Division of Rheumatology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Frey
authors.affiliation: Division of Visceral and Transplantation Surgery, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Brockmann
authors.affiliation: Division of Nephrology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Fehr
authors.affiliation: Division of Nephrology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: T F
authors.initials: TF
authors.lastname: Mueller
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Saleh
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: von Eckardstein
authors.affiliation: Graf Biostatistics, Winterthur, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.affiliation: Division of Nephrology, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: R P
authors.initials: RP
authors.lastname: Wüthrich
mesh_terms: D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab