Evidence map›Paper›PMID 23021595›Full record

ArticleHead & face medicine2012

Short time administration of antirheumatic drugs - methotrexate as a strong inhibitor of osteoblast's proliferation in vitro.

Tobias Annussek, Johannes Kleinheinz, Szuwart Thomas, Ulrich Joos, Kai Wermker

Open access · goldAbstract readComparative Study
In one paragraph

Article in Head & face medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.2field-weighted citation impact, top 38% 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

6 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Osteonecrosis of the Jaw in the Absence of Antiresorptive or Antiangiogenic Exposure: A Series of 6 Cases.Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons · 2017
    Article
  6. 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 1 country.

Tobias AnnussekDepartment of Cranio-Maxillofacial Surgery, University Hospital Muenster, Germany. tobias.annussek@ukmuenster.de
Johannes Kleinheinz
Szuwart Thomas
Ulrich Joos
Kai Wermker
University Hospital Münster · DEUniversity of Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDue to increasing use of disease modifying antirheumatic drugs (DMARDs) as first line therapy in rheumatic diseases, dental and maxillofacial practitioner should be aware of drug related adverse events. Especially effects on bone-metabolism and its cells are discussed controversially. Therefore we investigate the in vitro effect of short time administration of low dose methotrexate (MTX) on osteoblasts as essential part of bone remodelling cells.

methodsPrimary bovine osteoblasts (OBs) were incubated with various concentrations of MTX, related to tissue concentrations, over a period of fourteen days by using a previously established standard protocol. The effect on cell proliferation as well as mitochondrial activity was assessed by using 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay, imaging and counting of living cells. Additionally, immunostaining of extracellular matrix proteins was used to survey osteogenic differentiation.

resultsAll methods indicate a strong inhibition of osteoblast`s proliferation by short time administration of low dose MTX within therapeutically relevant concentrations of 1 to 1000 nM, without affecting cell differentiation of middle-stage differentiated OBs in general. More over a significant decrease of cell numbers and mitochondrial activity was found at these MTX concentrations. The most sensitive method seems to be the MTT-assay. MTX-concentration of 0,01 nM and concentrations below had no inhibitory effects anymore.

conclusionEven low dose methotrexate acts as a potent inhibitor of osteoblast's proliferation and mitochondrial metabolism in vitro, without affecting main differentiation of pre-differentiated osteoblasts. These results suggest possible negative effects of DMARDs concerning bone healing and for example osseointegration of dental implants. Especially the specifics of the jaw bone with its high vascularisation and physiological high tissue metabolism, suggests possible negative effects of DMARD therapy concerning oral and cranio-maxillofacial bone surgery as could be seen in a similar way in bisphosphonate related osteonecrosis of the jaw.

Indexed as

AnimalsAntirheumatic AgentsArthritis, RheumatoidBone RemodelingCattleCell DivisionCell ProliferationCells, CulturedDose-Response Relationship, DrugDrug Administration ScheduleHumansImmunohistochemistryIn Vitro TechniquesMethotrexateOsteoblastsOsteocalcinAntirheumatic AgentsMethotrexateOsteocalcin

Identifiers

PMID23021595
PMCPMC3517327
OpenAlexW2101024570

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.