Evidence map›Paper›PMID 28664276›Full record

ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017

Surgically treated osteonecrosis and osteomyelitis of the jaw and oral cavity in patients highly adherent to alendronate treatment: a nationwide user-only cohort study including over 60,000 alendronate users.

P A Eiken, D Prieto-Alhambra, R Eastell, B Abrahamsen

Abstract read
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Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 4 pooled it
1.6field-weighted citation impact, top 14% 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

24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023
    Guideline
  3. Pooled it
  4. Fracture risk following intermission of osteoporosis therapy.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Pooled it
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Treatment for osteoporosis and risk of osteonecrosis of the jaw among female patients in the United Kingdom Clinical Practice Research Datalink.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
    Article
  10. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023
    Article
  11. Long-term consequences of osteoporosis therapy with bisphosphonates.Archives of endocrinology and metabolism · 2023
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Side effects of drugs for osteoporosis and metastatic bone disease.British journal of clinical pharmacology · 2019
    Review
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

4 authors at 4 institutions in 3 countries.

P A EikenDepartment of Cardiology, Nephrology and Endocrinology, North Zealand Hospital, Hillerød, Dyrehavevej 29, 3400, Hillerød, Denmark. piei@regionh.dk.
D Prieto-AlhambraMusculoskeletal Pharmaco and Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK.
R EastellAcademic Unit of Bone Metabolism (AUBM), University of Sheffield, Herries Road, Sheffield, S5 7AU, UK.
B AbrahamsenDepartment of Clinical Research, Odense Patient Data Explorative Network, University of Southern Denmark, J.B. Winsløws Vej 9 A, 3. Sal, 5000, Odense, Denmark.
Holbæk Sygehus · DKInstitut Universitari d'Investigació en Atenció Primària Jordi Gol · ESUniversity of Sheffield · GBZealand University Hospital · DK

Funding

Medical Research Council MR/K006312/1
6 · The paper itself

Abstract

Osteonecrosis of the jaw (ONJ) is rare (2.53/10,000 person-years) among alendronate users, but long-term and compliant use are associated with an increased risk of surgically treated ONJ. Risk of surgically treated ONJ is higher in patients with rheumatoid diseases and use of proton pump inhibitors.

introductionONJ is a rare event in users of oral bisphosphonates. Our aims were to evaluate if the risk of surgically treated ONJ increases with longer or more compliant treatment with alendronate for osteoporosis and to identify risk factors for surgically treated ONJ.

methodsOpen nationwide register-based cohort study containing one nested case-control study. Patients were treatment-naïve incident users of alendronate 1996-2007 in Denmark, both genders, aged 50-94 at the time of beginning treatment (N = 61,990). Participants were followed to 31 December 2013.

resultsOver a mean of 6.8 years, 107 patients received surgery for ONJ or related conditions corresponding to an incidence rate of 2.53 (95% confidence interval (CI) 2.08 to 3.05) per 10,000 patient years. Recent use was associated with an adjusted odds ratio (OR) 4.13 (95% CI 1.94 to 8.79) compared to past use. Similarly, adherent users (medication possession ratio (MPR) >50%) were at two to threefold increased risk of ONJ compared to low adherence (MPR <50%), and long-term (>5 years) use was related with higher risk (adjusted OR 2.31 (95% CI (1.14 to 4.67)) than shorter-term use. History of rheumatoid disorders and use of proton pump inhibitors were independently associated with surgically treated ONJ.

conclusionsOur data suggest that recent, long-term, and compliant uses of alendronate are associated with an increased risk of surgically treated ONJ. Nevertheless, the rates remain low, even in long-term adherent users. ONJ risk appears higher in patients with conditions likely to indirectly affect the oral mucosa.

Indexed as

Administration, OralAgedAged, 80 and overAlendronateBisphosphonate-Associated Osteonecrosis of the JawBone Density Conservation AgentsCase-Control StudiesCohort StudiesComorbidityDenmarkDrug Administration ScheduleFemaleHumansMaleMiddle AgedOsteomyelitisAlendronateBone Density Conservation AgentsAlendronateBiphosphonatesEpidemiologyOsteomyelitis of the jawOsteonecrosis of the jawRisk factorsSurgery

Identifiers

PMID28664276
OpenAlexW2733593079

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.