Journal article
Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.
- Tsourdi E Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
- Zillikens MC Bone Center, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
- Meier C Division of Endocrinology, Diabetology and Metabolism, University Hospital and University of Basel, Switzerland.
- Body JJ Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
- Gonzalez Rodriguez E Interdisciplinary Centre for Bone diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
- Anastasilakis AD Department of Endocrinology, General Military Hospital, Thessaloniki, Greece.
- Abrahamsen B OPEN, University of Southern Denmark, Odense, Denmark.
- McCloskey E 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.
- Hofbauer LC Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
- Guañabens N Department of Rheumatology, Metabolic Bone Diseases Unit, Hospital Clínic, Barcelona, CIBERehd, University of Barcelona, Barcelona, Spain.
- Obermayer-Pietsch B Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz.
- Ralston SH Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK.
- Eastell R Mellanby Centre for Bone Research, University of Sheffield, UK.
- Pepe J Department of clinical, internal, anesthesiology and cardiovascular sciences, "Sapienza" University of Rome, Italy.
- Palermo A Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
- Langdahl B Medical Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
- 2020-10-26
Published in:
- The Journal of clinical endocrinology and metabolism. - 2020
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1210/clinem/dgaa756
- PMID 33103722
- Persistent URL
- https://folia.unifr.ch/global/documents/201748
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