| アブストラクト | Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-kappaB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-kappaB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations. |
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| ジャーナル名 | Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA |
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| 投稿日 | 2023/7/5 |
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| 投稿者 | Oteo-Alvaro, Angel; Garcia, Carlos Goicoechea; Sanchez, Alejandra Inocencio; Santamaria, Carlo Alemany; de Diego-Adelino, Javier |
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| 組織名 | Unidad de Metabolismo Oseo, HM Universitario de Madrid, HM Hospitales, Madrid,;Spain. angel_oteo@telefonica.net.;Departamento Ciencias Basicas de La Salud, Area de Farmacologia Y Nutricion,;Facultad de Ciencias de La Salud, High Performance Research Group in Experimental;Pharmacology (PHARMAKOM), Universidad Rey Juan Carlos, Unidad Asociada I+D+I Al;Instituto de Quimica Medica (CSIC), 28933, Alcorcon, Madrid, Spain.;Servicio de Rehabilitacion Y Medicina Fisica, Hospital General Universitario;Gregorio Maranon, Madrid, Spain.;Servicio de Psiquiatria. Institut d'Investigacio Biomedica Sant Pau (IIB-Sant;Pau)Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Hospital;de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona (UAB), Barcelona,;Spain. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37405407/ |
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