An observational study in Peri-Implantitis and Peri-implant Mucositis, Hypoxia and Ferroptosis, sponsored by Ege University. Completed at 1 site in Turkey. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-07.
Sponsored by Ege University · Observational
Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. This study investigates whether low oxygen levels (hypoxia) in the peri-implant environment influence ferroptosis, a type of cell death associated with oxidative stress. The research focuses on three key biomarkers: hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA).
A total of 45 participants with 62 dental implants were included in the study. They were divided into three groups: peri-implant health, peri-implant mucositis, and peri-implantitis. Peri-implant crevicular fluid (PICF) samples were collected, and the levels of HIF-1α, GPX-4, and MDA were measured using laboratory tests.
The study aims to determine whether hypoxia affects ferroptosis-related pathways by altering GPX-4 and MDA levels. Understanding these mechanisms could provide new insights into peri-implant disease progression and help develop improved treatment strategies.
Peri-implant diseases are characterized by an inflammatory response leading to progressive bone loss around dental implants. While microbial biofilms and host immune responses contribute to disease progression, recent studies have suggested that programmed cell death pathways, including ferroptosis, may also play a role. Ferroptosis is an iron-dependent form of non-apoptotic cell death that is regulated by GPX-4, a key enzyme that prevents lipid peroxidation, and MDA, a biomarker of oxidative damage. Hypoxia, a common feature in peri-implant disease, is known to modulate oxidative stress and inflammatory responses through HIF-1α, but its role in ferroptosis remains unclear.
This cross-sectional study aims to evaluate the relationship between hypoxia and ferroptosis in peri-implant diseases by measuring the levels of HIF-1α, GPX-4, and MDA in peri-implant crevicular fluid (PICF). A total of 45 participants with 62 dental implants were included in the study, categorized into peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (PP) groups. PICF samples were collected using standardized paper strips, and biomarker levels were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Kruskal-Wallis and Spearman correlation tests, were performed to assess differences among groups and potential associations between biomarkers.
The findings demonstrated that MDA levels were significantly lower in the peri-implantitis and peri-implant mucositis groups compared to peri-implant health, while GPX-4 levels were elevated in peri-implant mucositis and decreased in peri-implantitis. HIF-1α levels showed no significant differences among groups, but a positive correlation was observed between HIF-1α and GPX-4, suggesting a potential interaction between hypoxia and ferroptotic regulation in peri-implant tissues. These results imply that hypoxic conditions in peri-implant diseases may inhibit ferroptosis by modulating GPX-4 activity and reducing lipid peroxidation.
The study provides novel insights into the pathophysiology of peri-implant diseases, suggesting that the peri-implant microenvironment may exhibit unique regulatory mechanisms affecting ferroptotic pathways. While these findings contribute to our understanding of peri-implant disease pathogenesis, further longitudinal studies are needed to establish causal relationships and explore potential therapeutic strategies targeting hypoxia-ferroptosis interactions.
488 studies on the registry are indexed under Mucositis; 70 are open to participants now.
This study's enrollment of 45 is below the median of 102 across 66 observational studies indexed under Mucositis.
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This study included individuals with at least one dental implant, recruited from the Department of Periodontology, Ege University, Faculty of Dentistry. Participants were selected based on specific eligibility criteria, ensuring that they had an implant functioning for at least one year and no history of systemic diseases or recent periodontal treatments. The study population consisted of individuals diagnosed with peri-implant health, peri-implant mucositis, or peri-implantitis, classified according to clinical and radiographic findings. All participants provided informed consent before sample collection.
Exclusion Criteria:
Diabetes mellitus Rheumatoid arthritis Cardiovascular disorders Immunological disorders Mucocutaneous diseases Contagious or communicable diseases
Immunosuppressants Steroids Non-steroidal anti-inflammatory drugs (NSAIDs) Antiepileptics Calcium channel blockers Beta-blockers Anticoagulants Hormonal contraceptives Nutritional supplements
Participants with no clinical signs of peri-implant disease. These individuals exhibit healthy peri-implant soft tissues with no bleeding on probing (BOP), probing depth (PD) ≤ 4 mm, and no radiographic bone loss.
Participants diagnosed with peri-implant mucositis, characterized by bleeding on probing (BOP) and/or signs of inflammation (redness, swelling), but without radiographic bone loss beyond early remodeling.
Participants diagnosed with peri-implantitis, defined by increased probing depth (PD \> 5 mm), bleeding on probing (BOP) or suppuration, and radiographic evidence of bone loss beyond initial remodeling.
HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid
Measurement of hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA) levels in peri-implant crevicular fluid using enzyme-linked immunosorbent assay (ELISA) to assess their association with peri-implant health, mucositis, and peri-implantitis.
Time frame: Cross-sectional measurement at a single time point
Plan to share: Undecided — The decision regarding individual participant data (IPD) sharing has not yet been finalized. Factors such as data privacy regulations, institutional policies, and publication plans will be considered before determining whether and to what extent the collected IPD will be shared.
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