Evidence map›Paper›PMID 31175404›Full record

SynthesisOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2019

Fracture risk following intermission of osteoporosis therapy.

E M Dennison, C Cooper, J A Kanis, O Bruyère, S Silverman, E McCloskey, B Abrahamsen, D Prieto-Alhambra, S Ferrari, IOF Epidemiology/Quality of Life Working Group

Open access · greenAbstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 5 pooled it
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 5 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Guideline
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  4. Pooled it
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  6. Review
  7. Clarifying clinically treatment-naive status for osteoporosis patients.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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  9. Article
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  17. Osteoporosis in 2022: Care gaps to screening and personalised medicine.Best practice & research. Clinical rheumatology · 2022
    Review
  18. Review
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 7 countries.

E M DennisonMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK.
C CooperMRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK. cc@mrc.soton.ac.uk.
J A KanisCentre for Metabolic Bone Diseases, University of Sheffield Medical School, University of Sheffield, Sheffield, UK.
O BruyèreWorld Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Ageing, Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
S SilvermanCedars-Sinai/UCLA Medical Center and OMC Clinical Research Center, Beverly Hills, CA, USA.
E McCloskeyAcademic Unit of Bone Metabolism, Department of Oncology and Metabolism, The Mellanby Centre For Bone Research, University of Sheffield, Sheffield, UK.
B AbrahamsenDepartment of Medicine, Holbaek Hospital, Holbaek, Denmark.
D Prieto-AlhambraNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
S FerrariDivision of Bone Disease, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland.
IOF Epidemiology/Quality of Life Working Group
Cedars-Sinai Medical Center · USNuffield Orthopaedic Centre · GBUniversitat Autònoma de Barcelona · ESMRC Lifecourse Epidemiology Unit · GBUniversity Hospital of Geneva · CHUniversity of Liège · BEUniversity of Southern Denmark · DK

Funding

Medical Research Council G0400491Medical Research Council MC_U147585819Medical Research Council MC_U147585824Medical Research Council MC_UP_A620_1014Medical Research Council MC_UU_12011/1Versus Arthritis 19583
6 · The paper itself

Abstract

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.

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.

Indexed as

Age FactorsBisphosphonate-Associated Osteonecrosis of the JawBone DensityBone Density Conservation AgentsClinical Decision-MakingDenosumabDiphosphonatesDrug Administration ScheduleHumansOsteoporosis, PostmenopausalOsteoporotic FracturesRisk AssessmentRisk FactorsWithholding TreatmentBone Density Conservation AgentsDenosumabDiphosphonatesAtypical fractureBisphosphonatesDenosumabDrug holiday

Identifiers

PMID31175404
OpenAlexW2954352310

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.