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Fracture risk following intermission of osteoporosis therapy

Fracture risk following intermission of osteoporosis therapy
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 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.
0937-941X
1-11
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Kanis, J.A.
ec5ad011-1ed5-43e9-acac-b0d4f535f5b1
Bruyère, O.
ba727e54-ca17-4fa8-be3d-4729fb4b8c0d
Silverman, S.
dfe0f214-17ef-41de-b403-7e2b3105f178
McCloskey, E.
6d3df4aa-b438-4a83-bd06-06b6cbe3980f
Abrahamsen, B.
fee8b1eb-c267-4d2a-952a-d1b9f20d0125
Prieto-Alhambra, D.
051113cd-2da1-4e0d-aa4b-d7b1fe63cd12
Ferrari, S.L.
b5425bf6-92cc-4d6e-be9d-a722495d778a
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Kanis, J.A.
ec5ad011-1ed5-43e9-acac-b0d4f535f5b1
Bruyère, O.
ba727e54-ca17-4fa8-be3d-4729fb4b8c0d
Silverman, S.
dfe0f214-17ef-41de-b403-7e2b3105f178
McCloskey, E.
6d3df4aa-b438-4a83-bd06-06b6cbe3980f
Abrahamsen, B.
fee8b1eb-c267-4d2a-952a-d1b9f20d0125
Prieto-Alhambra, D.
051113cd-2da1-4e0d-aa4b-d7b1fe63cd12
Ferrari, S.L.
b5425bf6-92cc-4d6e-be9d-a722495d778a

Dennison, E.M., Cooper, C., Kanis, J.A., Bruyère, O., Silverman, S., McCloskey, E., Abrahamsen, B., Prieto-Alhambra, D. and Ferrari, S.L. (2019) Fracture risk following intermission of osteoporosis therapy. Osteoporosis International, 1-11. (doi:10.1007/s00198-019-05002-w).

Record type: Article

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.

Text
IOF WG Interruption accepted March 2019 - Accepted Manuscript
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More information

Accepted/In Press date: 26 March 2019
e-pub ahead of print date: 7 June 2019

Identifiers

Local EPrints ID: 429724
URI: http://eprints.soton.ac.uk/id/eprint/429724
ISSN: 0937-941X
PURE UUID: 98ecde2c-a724-45f2-b473-4fb6fb26933c
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

Catalogue record

Date deposited: 04 Apr 2019 16:30
Last modified: 26 Nov 2021 05:32

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Contributors

Author: E.M. Dennison ORCID iD
Author: C. Cooper ORCID iD
Author: J.A. Kanis
Author: O. Bruyère
Author: S. Silverman
Author: E. McCloskey
Author: B. Abrahamsen
Author: D. Prieto-Alhambra
Author: S.L. Ferrari

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