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Bipolar Depressive Recurrence Following Treatment with the Human Monoclonal Antibody Denosumab: A Case Report

      Designed to treat osteoporosis, denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappaB ligand (NF-κB) (RANKL, a member of the tumor necrosis factor superfamily of ligands and receptors). It blocks the binding of RANKL to RANK and avoids the activation of NF-κB, a protein complex involved in cellular signaling (
      • Tornatore L.
      • Thotakura A.K.
      • Bennett J.
      • Moretti M.
      • Franzoso G.
      The nuclear factor kappa B signaling pathway: Integrating metabolism with inflammation.
      ). Denosumab reduces the formation, function, and survival of osteoclasts, resulting in decreased bone resorption and increased bone density. Its effectiveness in osteoporosis has been shown in different clinical trials (
      • Cummings S.R.
      • San M.J.
      • McClung M.R.
      • Siris E.S.
      • Eastell R.
      • Reid I.R.
      • et al.
      Denosumab for prevention of fractures in postmenopausal women with osteoporosis.
      ,
      • McClung M.R.
      • Lewiecki E.M.
      • Cohen S.B.
      • Bolognese M.A.
      • Woodson G.C.
      • Moffett A.H.
      • et al.
      Denosumab in postmenopausal women with low bone mineral density.
      ,
      • Lewiecki E.M.
      • Miller P.D.
      • McClung M.R.
      • Cohen S.B.
      • Bolognese M.A.
      • Liu Y.
      • et al.
      Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD.
      ,
      • Bone H.G.
      • Bolognese M.A.
      • Yuen C.K.
      • Kendler D.L.
      • Wang H.
      • Liu Y.
      • San Martin J.
      Effects of denosumab on bone mineral density and bone turnover in postmenopausal women.
      ). In addition to suppressing osteoclastogenesis, the RANKL/NF-κB system plays a central role in the inflammatory response (
      • Martin T.J.
      Paracrine regulation of osteoclast formation and activity: Milestones in discovery.
      ), including modulation of neuroinflammation (
      • Nadjar A.
      • Bluthe R.M.
      • May M.J.
      • Dantzer R.
      • Parnet P.
      Inactivation of the cerebral NFkappaB pathway inhibits interleukin-1beta-induced sickness behavior and c-Fos expression in various brain nuclei.
      ). However, no neuropsychiatric adverse events have been described with denosumab treatment up to now.
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