Elena Tsourdi1,2, M Carola Zillikens3, Christian Meier4, Jean-Jacques Body5, Elena Gonzalez Rodriguez6, Athanasios D Anastasilakis7, Bo Abrahamsen8,9,10, Eugene McCloskey11, Lorenz C Hofbauer1,2,12, Nuria Guañabens13, Barbara Obermayer-Pietsch14,15, Stuart H Ralston16, Richard Eastell17, Jessica Pepe18, Andrea Palermo19, Bente Langdahl20. 1. Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany. 2. Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany. 3. Bone Center, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. 4. Division of Endocrinology, Diabetology and Metabolism, University Hospital and University of Basel, Switzerland. 5. Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium. 6. Interdisciplinary Centre for Bone diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 7. Department of Endocrinology, General Military Hospital, Thessaloniki, Greece. 8. OPEN, University of Southern Denmark, Odense, Denmark. 9. Department of Medicine, Holbæk Hospital, Holbæk, Denmark. 10. NDORMS, University of Oxford, Oxford, UK. 11. Academic Unit of Bone Metabolism, Department of Oncology and Metabolism, The Mellanby Centre For Bone Research, The Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK. 12. Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany. 13. Department of Rheumatology, Metabolic Bone Diseases Unit, Hospital Clínic, Barcelona, CIBERehd, University of Barcelona, Barcelona, Spain. 14. Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz. 15. Center for Biomarker Research in Medicine (CBmed),-Graz, Austria. 16. Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK. 17. Mellanby Centre for Bone Research, University of Sheffield, UK. 18. Department of clinical, internal, anesthesiology and cardiovascular sciences, "Sapienza" University of Rome, Italy. 19. Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy. 20. Medical Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
CONTEXT: Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. METHODS: A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. RESULTS: Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. CONCLUSIONS: A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.
CONTEXT: Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. METHODS: A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. RESULTS: Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. CONCLUSIONS: A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.
Authors: Katherine A P Ralston; Jonathan Phillips; Amrey Krause; Barbara Hauser; Stuart H Ralston Journal: Calcif Tissue Int Date: 2022-02-13 Impact factor: 4.000
Authors: Athanasios D Anastasilakis; Stergios A Polyzos; Maria P Yavropoulou; Natasha M Appelman-Dijkstra; Charikleia Ntenti; Stylianos Mandanas; Athanasios Papatheodorou; Polyzois Makras Journal: Calcif Tissue Int Date: 2021-01-02 Impact factor: 4.333