Evidence map›Paper›PMID 26254598›Full record

ArticleClinical oral investigations2016

Mouse anti-RANKL antibody delays oral wound healing and increases TRAP-positive mononuclear cells in bone marrow.

Shinichiro Kuroshima, Zeina Al-Salihi, Junro Yamashita

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical oral investigations, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  4. Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025
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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

3 authors at 2 institutions in 2 countries.

Shinichiro KuroshimaDepartment of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, Nagasaki, 852-8588, Japan.
Zeina Al-SalihiDepartment of Biologic and Materials Sciences, Prosthodontic Division, School of Dentistry, University of Michigan, 1011 North University Ave., Ann Arbor, MI, 48109, USA.
Junro YamashitaDepartment of Biologic and Materials Sciences, Prosthodontic Division, School of Dentistry, University of Michigan, 1011 North University Ave., Ann Arbor, MI, 48109, USA. yamashit@umich.edu.
University of Michigan–Ann Arbor · USNagasaki University · JP

Funding

Antiresorptive-Induced Fragile Oral Wound HealingR01DE023538 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YAMASHITA, JUNRO · 2013 to 2017
$1.4M
NIDCR NIH HHS R01 DE023538
6 · The paper itself

Abstract

objectivesDenosumab, a human monoclonal antibody (mAb) that neutralizes receptor activator for nuclear factor κB ligand (RANKL), is associated with osteonecrosis of the jaw. However, the effect of denosumab on oral wounds is unclear. The aim was to determine the effect of anti-RANKL mAb on oral wounds and bone marrow. MATERIALS AND

methodsThe direct effect of the mAb on fibroblasts, macrophages, and osteoclasts were assessed in vitro. In vivo, mouse anti-RANKL mAb was administered to mice for 9 weeks prior to palatal bone denudation surgery. Mice were euthanized 3 weeks post-surgery, and wound healing was histomorphometrically analyzed. Long bones were assessed using micro-computed tomography, quantitative real-time polymerase chain reaction, and flow cytometry.

resultsThe mAb had no effect on macrophages and fibroblasts but significantly suppressed osteoclast proliferation in vitro. The mAb treatment significantly increased bone mass by suppressing osteoclasts in vivo. The expression of pro-osteoclastic genes was promoted in the bone marrow of the mAb-administered animals. Consistently, the mAb significantly induced the development of tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (MNCs) but not osteoclasts in bone marrow. The mAb treatment had no effect on gross healing of the palatal wounds. However, significant inflammation was retained in the connective tissue facing the once denuded bone surface.

conclusionsRepair of the damaged palate was delayed, and significant inflammation was sustained in the connective tissue by anti-RANKL mAb treatment. CLINICAL RELEVANCE: Denosumab impairs osteoclastic bone repair. Care should be exercised to minimize osseous trauma when invasive procedures are performed on patients taking denosumab.

Indexed as

Bone Marrow CellsRANK LigandAnimalsAntibodiesBone MarrowDenosumabFibroblastsHumansMacrophagesMiceOsteoclastsX-Ray MicrotomographyAntibodiesDenosumabRANK LigandAntiresorptivesInflammationMouse anti-RANKL monoclonal antibodyTRAP-positive mononuclear cellsWound healing

Identifiers

PMID26254598
PMCPMC4840226
OpenAlexW1920239374

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.