Evidence map›Paper›PMID 40231895›Full record

ArticleJournal of periodontology2025

Peri-implant inflammation increases the risk of osteonecrosis in mice treated with bisphosphonate.

Ana Bujila, Davi N A Silva, Sepehr Monajemzadeh, Taciane M da Silveira, Naseim Elzakra, Maísa Casarin, Kimberly Flores, Clara Magyar, Julie Marchesan, Reuben Kim and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of periodontology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

12 authors.

Ana BujilaSection of Periodontics, School of Dentistry, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0009-0002-8121-4096
Davi N A SilvaSection of Periodontics, School of Dentistry, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-4292-0118
Sepehr MonajemzadehSection of Periodontics, School of Dentistry, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-1953-5975
Taciane M da SilveiraSchool of Dentistry, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.ORCID https://orcid.org/0000-0002-1863-4146
Naseim ElzakraSection of Oral and Maxillofacial Radiology, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-6829-5461
Maísa CasarinSchool of Dentistry, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.ORCID https://orcid.org/0000-0002-3750-5091
Kimberly FloresDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0009-0002-0173-317X
Clara MagyarDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0003-2261-0187
Julie MarchesanDepartment of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0003-0610-3193
Reuben KimSchool of Dentistry, Section of Restorative Dentistry, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0001-5635-7728
Sotirios TetradisSection of Oral and Maxillofacial Radiology, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-0157-1855
Flavia Q PirihSection of Periodontics, School of Dentistry, University of California, Los Angeles, California, USA.ORCID https://orcid.org/0000-0003-1670-7345

Funding

Pathophysiologic Mechanisms of Bisphosphonate Related Osteonecrosis of the JawsR01DE019465 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TETRADIS, SOTIRIOS · 2009 to 2024
$5.4M
Mouse Genome-Wide Association Studies in LPS-Induced Bone LossR21DE023901 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIRIH, FLAVIA · 2014 to 2015
$407k
Osteomucosal healing and immunity in medication-related osteonecrosis of the jawR56DE033281 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GWACK, YOUSANG, KIM, REUBEN HAN-KYU · 2023 to 2023
$390k
NIDCR NIH HHS R01 DE019465NIDCR NIH HHS R21 DE023901NIDCR NIH HHS R56 DE033281
6 · The paper itself

Abstract

backgroundBisphosphonates (BPs) are effective in managing bone diseases due to their anti-resorptive properties but are linked to medication-related osteonecrosis of the jaw (MRONJ), particularly concerning dental implants. This study explored the combined impact of ligature-induced peri-implant inflammation and zoledronic acid (ZA), a BP, using a murine model.

methodsTwenty-four mice underwent bilateral maxillary molar extractions and implant placements, with ZA or vehicle treatment and ligature placement on the left side. Two groups were defined: group 1 (vehicle-treated) with control (Veh-C) and ligature (Veh-L) implants, and group 2 (ZA-treated) with control (ZA-C) and ligature (ZA-L) implants. Clinical, micro-CT, histological, and immunohistochemical analyses were performed. We hypothesized that peri-implant inflammation elevates MRONJ risk with BP treatment.

resultsLigature groups showed increased soft tissue edema compared to controls, without differences between vehicle and ZA treatments. The Veh-L group exhibited significantly greater bone loss than other groups. Histology showed higher inflammatory infiltrate in ligature groups. Osteocyte empty lacunae and osteonecrosis were significantly greater in ZA-L. Picrosirius red staining revealed disorganized collagen fibers and separation in ZA-L. Immunohistochemistry showed increased neutrophils (NIMP-R14+) and monocytes/macrophages (CD11b+) in the ligature groups, with no significant differences between Veh-C and ZA-C.

conclusionLigature treatment enhances peri-implant inflammation, with ZA heightening the risk of MRONJ. These findings highlight the critical importance of early detection and management of peri-implant inflammation in patients undergoing BP therapy, particularly those at high risk of MRONJ. Clinicians should emphasize preventive measures, such as regular monitoring of peri-implant health and reducing local inflammatory triggers, to mitigate the adverse effects of BPs on peri-implant bone health. PLAIN LANGUAGE SUMMARY: Dental implants are a reliable solution to replace missing teeth. However, like natural teeth, implants can develop inflammation around them-peri-implantitis. Our study found that, when this inflammation occurs in patients taking BPs (a medication commonly used to treat osteoporosis and other bone diseases), the risk of developing a serious jaw condition called osteonecrosis (ONJ) increases significantly. ONJ prevents the jawbone from healing properly, leading to pain, infection, and even exposed bone. These findings highlight the importance of preventing and managing inflammation around dental implants to reduce the risk of complications, especially in patients taking BPs. Our research suggests regular dental check-ups and proper oral hygiene can help maintain implant health and prevent severe bone-related conditions. Patients and healthcare providers can take proactive steps to improve long-term oral health outcomes by understanding these risks.

Indexed as

Bisphosphonate-Associated Osteonecrosis of the JawBone Density Conservation AgentsDental ImplantsDiphosphonatesPeri-ImplantitisZoledronic AcidAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLRisk FactorsX-Ray MicrotomographyBone Density Conservation AgentsDental ImplantsDiphosphonatesZoledronic Acidalveolar bone lossesbone tissuedental implantosteoclastperi‐implantitis

Identifiers

PMID40231895
PMCPMC12353669

What OpenQuestion holds

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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.