Fracture risk following intermission of osteoporosis therapy
Summary Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteo...
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| Published in: | Osteoporosis International Vol. 30; no. 9; pp. 1733 - 1743 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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London
Springer Science and Business Media LLC
01.09.2019
Springer London Springer Nature B.V |
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| ISSN: | 0937-941X, 1433-2965, 1433-2965 |
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| Abstract | Summary
Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped.
Introduction
The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab.
Methods
Systematic review.
Results
Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture.
Conclusions
The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. |
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| AbstractList | Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped.
The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab.
Systematic review.
Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20-40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture.
The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped. Introduction: The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab. Methods: Systematic review. Results: Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture. Conclusions: The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. © 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. SummaryGiven the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped.IntroductionThe aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab.MethodsSystematic review.ResultsDiffering pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture.ConclusionsThe view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped.Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped.The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab.INTRODUCTIONThe aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab.Systematic review.METHODSSystematic review.Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20-40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture.RESULTSDiffering pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20-40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture.The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare.CONCLUSIONSThe view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. Summary Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped. Introduction The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab. Methods Systematic review. Results Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture. Conclusions The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. |
| Author | Serge Ferrari John A. Kanis Cyrus Cooper Stuart L. Silverman Olivier Bruyère Daniel Prieto-Alhambra Elaine M. Dennison Bo Abrahamsen Eugene V. McCloskey |
| Author_xml | – sequence: 1 givenname: E.M. surname: Dennison fullname: Dennison, E.M. organization: MRC Lifecourse Epidemiology Unit, University of Southampton – sequence: 2 givenname: C. surname: Cooper fullname: Cooper, C. email: cc@mrc.soton.ac.uk organization: MRC Lifecourse Epidemiology Unit, University of Southampton, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford – sequence: 3 givenname: J.A. surname: Kanis fullname: Kanis, J.A. organization: Centre for Metabolic Bone Diseases, University of Sheffield Medical School, University of Sheffield, Mary McKillop Health Institute, Australian Catholic University – sequence: 4 givenname: O. surname: Bruyère fullname: Bruyère, O. organization: World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Ageing, Department of Public Health, Epidemiology and Health Economics, University of Liège – sequence: 5 givenname: S. surname: Silverman fullname: Silverman, S. organization: Cedars-Sinai/UCLA Medical Center and OMC Clinical Research Center – sequence: 6 givenname: E. surname: McCloskey fullname: McCloskey, E. organization: Academic Unit of Bone Metabolism, Department of Oncology and Metabolism, The Mellanby Centre For Bone Research, University of Sheffield – sequence: 7 givenname: B. surname: Abrahamsen fullname: Abrahamsen, B. organization: Department of Medicine, Holbaek Hospital, OPEN, Institute of Clinical Research, University of Southern Denmark – sequence: 8 givenname: D. surname: Prieto-Alhambra fullname: Prieto-Alhambra, D. organization: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, GREMPAL Research Group, Idiap Jordi Gol and CIBERFes, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III – sequence: 9 givenname: S. surname: Ferrari fullname: Ferrari, S. organization: Division of Bone Disease, Faculty of Medicine, Geneva University Hospital |
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| OpenAccessLink | https://cir.nii.ac.jp/crid/1872555065574545408 |
| PMID | 31175404 |
| PQID | 2236326258 |
| PQPubID | 33762 |
| PageCount | 11 |
| ParticipantIDs | liege_orbi_v2_oai_orbi_ulg_ac_be_2268_246383 proquest_miscellaneous_2283109810 proquest_journals_2236326258 pubmed_primary_31175404 crossref_citationtrail_10_1007_s00198_019_05002_w crossref_primary_10_1007_s00198_019_05002_w springer_journals_10_1007_s00198_019_05002_w nii_cinii_1872555065574545408 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-09-01 |
| PublicationDateYYYYMMDD | 2019-09-01 |
| PublicationDate_xml | – month: 09 year: 2019 text: 2019-09-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | London |
| PublicationPlace_xml | – name: London – name: England |
| PublicationSubtitle | With other metabolic bone diseases |
| PublicationTitle | Osteoporosis International |
| PublicationTitleAbbrev | Osteoporos Int |
| PublicationTitleAlternate | Osteoporos Int |
| PublicationYear | 2019 |
| Publisher | Springer Science and Business Media LLC Springer London Springer Nature B.V |
| Publisher_xml | – name: Springer Science and Business Media LLC – name: Springer London – name: Springer Nature B.V |
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28 R Eastell (5002_CR25) 2011; 96 S Papapoulos (5002_CR34) 2012; 27 KE Naylor (5002_CR51) 2018; 29 5002_CR12 NB Watts (5002_CR13) 2008; 19 N Hassler (5002_CR27) 2015; 26 5002_CR53 PA Eiken (5002_CR73) 2017; 28 BL McNabb (5002_CR31) 2013; 28 JD Adachi (5002_CR46) 2017; 18 HG Bone (5002_CR19) 2013; 98 AA Khan (5002_CR67) 2015; 30 RA Adler (5002_CR10) 2016; 31 DM Black (5002_CR17) 2015; 30 LH Xu (5002_CR55) 2016; 27 JC Lo (5002_CR66) 2010; 68 C Reyes (5002_CR3) 2017; 28 DM Black (5002_CR58) 2010; 362 SB Woo (5002_CR68) 2006; 144 J Schilcher (5002_CR59) 2011; 364 M Whittaker (5002_CR6) 2012; 366 DM Black (5002_CR16) 2012; 27 AL Adams (5002_CR52) 2018; 33 P Anagnostis (5002_CR7) 2017; 101 DC Bauer (5002_CR49) 2014; 174 E Shane (5002_CR9) 2010; 25 MR McClung (5002_CR29) 2013; 24 J Schilcher (5002_CR60) 2015; 86 MR McClung (5002_CR43) 2017; 28 B Abrahamsen (5002_CR74) 2016; 353 DM Black (5002_CR39) 2006; 296 E Cairoli (5002_CR75) 2014; 25 G Bianchi (5002_CR14) 2012; 23 RE Marx (5002_CR65) 2003; 61 WS Choi (5002_CR72) 2017; 39 |
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Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis... Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies... SummaryGiven the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis... |
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| SubjectTerms | Age Factors Atypical fracture Bisphosphonate-Associated Osteonecrosis of the Jaw Bisphosphonate-Associated Osteonecrosis of the Jaw - epidemiology Bisphosphonate-Associated Osteonecrosis of the Jaw - etiology Bisphosphonates Bone Density Bone Density - physiology Bone Density Conservation Agents Bone Density Conservation Agents - administration & dosage Bone Density Conservation Agents - therapeutic use Bone loss Bone mineral density Bone strength Clinical Decision-Making Clinical Decision-Making - methods Decision making Denosumab Denosumab - administration & dosage Denosumab - therapeutic use Diphosphonates Diphosphonates - administration & dosage Diphosphonates - therapeutic use Drug Administration Schedule Drug holiday Endocrinology Femur Fractures Geriatrics Gériatrie Human health sciences Humans Immunotherapy info:eu-repo/classification/ddc/616 Medicine Medicine & Public Health Monoclonal antibodies Original Article Orthopedics Osteoporosis Osteoporosis, Postmenopausal Osteoporosis, Postmenopausal - drug therapy Osteoporosis, Postmenopausal - physiopathology Osteoporotic Fractures Osteoporotic Fractures - epidemiology Osteoporotic Fractures - prevention & control Pharmacokinetics Postmenopausal/drug therapy Public health, health care sciences & services Rheumatology Rhumatologie Risk Assessment Risk Assessment - methods Risk Factors Santé publique, services médicaux & soins de santé Sciences de la santé humaine Vertebrae Withholding Treatment |
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| Title | Fracture risk following intermission of osteoporosis therapy |
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