Evidence map›Paper›PMID 19036117›Full record

ArticleBritish journal of haematology2009

Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis.

Mark A Scheper, Ashraf Badros, Risa Chaisuparat, Kevin J Cullen, Timothy F Meiller

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in British journal of haematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
6.4field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 155 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Zoledronic acid affects the process ofFrontiers in cellular and infection microbiology · 2023
    Article
  14. Article
  15. Frontiers in cellular and infection microbiology · 2022
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  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

5 authors at 2 institutions in 2 countries.

Mark A ScheperDepartment of Oncology and Diagnostic Sciences, Dental School, University of Maryland Medical Center, Baltimore, MD 21201, USA. mscheper@umaryland.edu
Ashraf Badros
Risa Chaisuparat
Kevin J Cullen
Timothy F Meiller
University of Maryland, Baltimore · USUniversity of Dental Medicine · MM

Funding

UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANTP30CA134274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI FEYRUZ VIRGILIA RASSOOL · 2008 to 2026
$51.0M
Clinical Research Career Development (RMI)K12RR023250 · NCRR · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2005 to 2009
$13.3M
NCI NIH HHS P30 CA134274NCRR NIH HHS K12 RR023250
6 · The paper itself

Abstract

Osteonecrosis of the jaw secondary to bisphosphonate infusion (zoledronic acid-ZA) is assumed to be a bone disease. This study investigated the effects of ZA on soft tissues using oral mucosal cells as an in vitro model of soft tissue cell death in the pathogenesis of bone necrosis. Human gingival fibroblast and keratinocyte cell lines were exposed to different concentrations of ZA (0.25-3 micromol/l), using 1 micromol/l as the expected baseline concentration. A dose-response effect on apoptosis and cell proliferation [Terminal deoxynucleotidyl transferase-mediated dUTP-Biotin End Labelling and Annexin V or Coulter counter and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), respectively] was observed with increasing ZA concentrations; both reversed using siRNA against caspase 3 or 9. Gene expression analysis using RT(2) Profiler polymerase chain reaction Arrays demonstrated the differential expression of multiple genes involved in apoptosis including those that encode TNF, BCL-2, Caspase, IAP, TRAF and Death Domain families. Western blot analysis confirmed the presence of activated forms of caspase 3 and 9 and underexpression of survivin protein expression. This study demonstrated that low concentrations of ZA rapidly and directly affected the oral mucosal tissues though the induction of a gene-regulated apoptotic process. These findings support the potential for soft tissue injury as an initiating/potentiating event for osteonecrosis.

Indexed as

ApoptosisBlotting, WesternBone Density Conservation AgentsCaspase 3Caspase 9Cell LineCell ProliferationDiphosphonatesDose-Response Relationship, DrugEpithelial CellsFibroblastsGene ExpressionGene Expression ProfilingGingivaHumansImidazolesBone Density Conservation AgentsCaspase 3Caspase 9DiphosphonatesImidazolesRNA, Small InterferingZoledronic Acid

Identifiers

PMID19036117
PMCPMC2739302
OpenAlexW2073500618

What OpenQuestion holds

Textmetadata
LicenceTDM
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.