Non-Cochrane · other · PM41624011

Specific gene expression patterns associated as reliable biomarkers for predicting dental implant successful osseointegration: a literature review and focused meta-analysis.

Serrato-Pedrosa Jesus Alejandro, Bocanegra-García Virgilio, Villanueva-Fierro Ignacio, et al. · Frontiers in physiology · 2025 · PubMed · doi:10.3389/fphys.2025.1682440

Findings

6 findings

Population
In vitro osteogenic cell models of dental implant osseointegrationModified titanium implant surfaceControl (unmodified) titanium surfaceRUNX2 gene expression (relative expression)
In vitro laboratory
Unresolved: the two extractors disagree on this row.
SMD 5.38 [0.66, 10.1]
Low
Downgraded: risk of bias, inconsistency, indirectness
4 studies · 32 participants
In vitro osteogenic cell models of dental implant osseointegrationModified titanium implant surfaceControl (unmodified) titanium surfaceRUNX2 gene expression (relative expression)
In vitro laboratory · Estimate as reported in the abstract (differs from Figure 2)
Unresolved: the two extractors disagree on this row.
SMD 2.58 [1.21, 3.95]
GRADE not reported
Studies not reported
In vitro, animal and human studies of pro-osteogenic markers on implant surfacesModified implant surfaceControl surfaceUpregulation of pro-osteogenic markers (RUNX2)
GRADE summary, all 13 primary studies
Unresolved: the two extractors disagree on this row.
Not applicable (13 primary studies, including 6 in vitro studies in meta-analysis); LOW
Low
Downgraded: risk of bias, imprecision, inconsistency, indirectness
13 studies
Dental implant failure and peri-implantitis (clinical, animal and in vitro studies)Increased RANKL/OPG ratioSuccessful osseointegration / normal ratioImplant failure (association with RANKL/OPG ratio)Table 3: 3 primary studies (clinical, animal, in vitro); Low certainty; upgraded one level for large effect (20-fold decrease in OPG)
Low
Downgraded: inconsistency, indirectness
3 studies
Dental implant failure and peri-implantitis (clinical, animal and in vitro studies)Elevated pro-inflammatory cytokines (IL-1B, IL-6, TNF-alpha)Successful osseointegration / normal expressionImplant failure (association with cytokine expression)Table 3: 11 primary studies (clinical, animal, in vitro); Low certainty; upgraded one level for large effect (20-fold increase in CCL5)
Low
Downgraded: risk of bias, inconsistency, indirectness
11 studies
In vitro and animal models of dental implant osseointegrationImplant surface modificationsControl or standard surfacesModulation of key signaling pathways (NF-kB, Wnt)Table 3: 7 primary studies (in vitro, animal); Very Low certainty
Very low
Downgraded: risk of bias, inconsistency, indirectness
7 studies

Included primary studies 60

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Manor 2021
A retrospective analysis of dental implantation under anticoagulant treatment.
PMID:32506326
20211 other reviewnot statednot extracted yet
Manor et al. (2021)
A retrospective analysis of dental implantation under anticoagulant treatment
DOI:10.1007/s00784-020-03389-z
20201 other reviewnot statednot extracted yet
Alkhoury 2020
Studies on the Mechanisms of Anti-Inflammatory Activity of Heparin- and Hyaluronan-Containing Multilayer Coatings-Targeting NF-κB…
PMID:32466274
2020this review onlynot statednot extracted yet
Bayandurov 2024
Selected osteointegration markers in different timeframes after dental implantation: findings and prognostic value.
PMID:38721304
2024this review onlynot statednot extracted yet
Bayandurov et al. (2024)
Selected osteointegration markers in different timeframes after dental implantation: findings and prognostic value
DOI:10.3389/abp.2024.12433
2024this review onlynot statednot extracted yet
Benalcazar-Jalkh 2023
Impact of implant thread design on insertion torque and osseointegration: a preclinical model.
PMID:36173722
2023this review onlynot statednot extracted yet
Cirera 2020
Osseointegration around dental implants biofunctionalized with TGFβ-1 inhibitor peptides: an in vivo study in beagle dogs.
PMID:32696084
2020this review onlynot statednot extracted yet
Cirera et al. (2020)
Osseointegration around dental implants biofunctionalized with TGFβ-1 inhibitor peptides: an in vivo study in beagle dogs
DOI:10.1007/s10856-020-06397-3
2020this review onlynot statednot extracted yet
da Cruz 2022
Laser surface treatment on Yttria-stabilized zirconia dental implants: Influence on cell behavior.
PMID:34278714
2022this review onlynot statednot extracted yet
da Cruz et al. (2022)
Laser surface treatment on Yttria‐stabilized zirconia dental implants: Influence on cell behavior
DOI:10.1002/jbm.b.34909
2021this review onlynot statednot extracted yet
dos Santos Trento 2020
Gene expression, immunohistochemical and microarchitectural evaluation of bone formation around two implant surfaces placed in bone…
PMID:33258065
2020this review onlynot statednot extracted yet
dos Santos Trento et al. (2020)
Gene expression, immunohistochemical and microarchitectural evaluation of bone formation around two implant surfaces placed in bone…
DOI:10.1186/s40729-020-00279-7
2020this review onlynot statednot extracted yet
Gil 2022
The effect of using Al2O3 and TiO2 in sandblasting of titanium dental implants
DOI:10.1557/s43578-022-00534-0
2022this review onlynot statednot extracted yet
Gnanajothi 2024
Inflammatory Status of Patients with Dental Implants of Different Microgeometry using ELISA: A Prospective Clinical Study
DOI:10.4103/jioh.jioh_47_24
2024this review onlynot statednot extracted yet
Han 2025a
Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants.
PMID:39579168
2025this review onlynot statednot extracted yet
Han et al. (2025a)
matched by author and year (probable)
NRthis review onlynot statednot extracted yet
Hergem et al. (2022)
Osteocalcin and Runx2 Expression in Anterior Maxillary Reconstructions Using Bone Xenografts Associated to Bone Marrow Aspirate Concentrate
DOI:10.4103/ccd.ccd_723_20
2022this review onlynot statednot extracted yet
Hergemoller 2022
Osteocalcin and Runx2 Expression in Anterior Maxillary Reconstructions Using Bone Xenografts Associated to Bone Marrow Aspirate Concentrate.
PMID:36213846
2022this review onlynot statednot extracted yet
Irandoust 2020
The interplay between bone healing and remodeling around dental implants.
PMID:32152332
2020this review onlynot statednot extracted yet
Irandoust and Müftü (2020)
The interplay between bone healing and remodeling around dental implants
DOI:10.1038/s41598-020-60735-7
2020this review onlynot statednot extracted yet
Jung 2021
The Effects of NF-kB Inhibition with p65-TMD-Linked PTD on Inflammatory Responses at Peri-implantitis Sites.
PMID:34169410
2021this review onlynot statednot extracted yet
Jung et al. (2021)
The Effects of NF-kB Inhibition with p65-TMD-Linked PTD on Inflammatory Responses at Peri-implantitis Sites
DOI:10.1007/s10753-021-01500-4
2021this review onlynot statednot extracted yet
Komatsu 2025
Advancing osseointegration research: A dynamic three-dimensional (3D) in vitro culture model for dental implants.
PMID:39873044
2025this review onlynot statednot extracted yet
Komatsu et al. (2025)
Advancing osseointegration research: A dynamic three-dimensional (3D) in vitro culture model for dental implants
DOI:10.1016/j.jds.2024.06.018
2025this review onlynot statednot extracted yet
Le 2021
Bioactivation Treatment with Mixed Acid and Heat on Titanium Implants Fabricated by Selective Laser Melting Enhances Preosteoblast Cell…
PMID:33921268
2021this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Le et al. (2021)
Bioactivation Treatment with Mixed Acid and Heat on Titanium Implants Fabricated by Selective Laser Melting Enhances Preosteoblast Cell…
DOI:10.3390/nano11040987
2021this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Lechner 2024
Osseointegration and osteoimmunology in implantology: assessment of the immune sustainability of dental implants using advanced…
PMID:38259068
2024this review onlynot statednot extracted yet
Lechner et al. (2024)
Osseointegration and osteoimmunology in implantology: assessment of the immune sustainability of dental implants using advanced…
DOI:10.1177/03000605231224161
2024this review onlynot statednot extracted yet
Maghsoudi 2022
Bone remodeling around dental implants after 1-1.5 years of functional loading: A retrospective analysis of two-stage implants.
PMID:35427440
2022this review onlynot statednot extracted yet
Maghsoudi et al. (2022)
Bone remodeling around dental implants after 1–1.5 years of functional loading: A retrospective analysis of two‐stage implants
DOI:10.1002/cre2.574
2022this review onlynot statednot extracted yet
Mukaddam 2025
TNF-α Activates NF-κB Signalling Pathway in MG-63 Cells on Titanium and Zirconia Implant Surfaces.
PMID:40004407
2025this review onlynot statednot extracted yet
Mukaddam et al. (2025)
TNF-α Activates NF-κB Signalling Pathway in MG-63 Cells on Titanium and Zirconia Implant Surfaces
DOI:10.3390/ma18040884
2025this review onlynot statednot extracted yet
Palermo 2022
Use of CGF in Oral and Implant Surgery: From Laboratory Evidence to Clinical Evaluation.
PMID:36499489
2022this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Palermo et al. (2022)
Use of CGF in Oral and Implant Surgery: From Laboratory Evidence to Clinical Evaluation
DOI:10.3390/ijms232315164
2022this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Romero-Gavilan 2023
Proteomic evaluation of human osteoblast responses to titanium implants over time.
PMID:36054528
2023this review onlynot statednot extracted yet
Romero-Gavilán et al. (2023)
Proteomic evaluation of human osteoblast responses to titanium implants over time
DOI:10.1002/jbm.a.37444
2022this review onlynot statednot extracted yet
Roy 2024
Biocompatibility of Subperiosteal Dental Implants: Changes in the Expression of Osteogenesis-Related Genes in Osteoblasts Exposed to…
PMID:38921520
2024this review onlynot statednot extracted yet
Roy et al. (2024)
Biocompatibility of Subperiosteal Dental Implants: Changes in the Expression of Osteogenesis-Related Genes in Osteoblasts Exposed to…
DOI:10.3390/jfb15060146
2024this review onlynot statednot extracted yet
Sadrkhah 2023
An In-Vivo Study on Nanostructured Ti Dental Implant Produced by Caliber Rolling and Surface Modification by SLActive
DOI:10.1007/s11837-023-06050-8
2023this review onlynot statednot extracted yet
Schluessel 2022
Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation.
PMID:35222398
2022this review onlynot statednot extracted yet
Schluessel et al. (2022)
Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation
DOI:10.3389/fimmu.2022.820843
2022this review onlynot statednot extracted yet
Shin 2022
Enhanced osseointegration of dental implants with reduced graphene oxide coating.
PMID:35313996
2022this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Shin et al. (2022)
Enhanced osseointegration of dental implants with reduced graphene oxide coating
DOI:10.1186/s40824-022-00257-7
2022this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Tang 2021
Role of the Hippo-YAP/NF-κB signaling pathway crosstalk in regulating biological behaviors of macrophages under titanium ion exposure.
PMID:33058278
2021this review onlynot statednot extracted yet
Tavelli 2024
Characterization of oral biomarkers during early healing at augmented dental implant sites.
PMID:39090529
2025this review onlynot statednot extracted yet
Tavelli et al. (2023)
Wound healing dynamics, morbidity, and complications of palatal soft‐tissue harvesting
DOI:10.1111/prd.12466
2022this review onlynot statednot extracted yet
Tavelli et al. (2024)
Characterization of oral biomarkers during early healing at augmented dental implant sites
DOI:10.1111/jre.13328
2024this review onlynot statednot extracted yet
Valente 2021
Collagen Fibres Orientation in the Bone Matrix around Dental Implants: Does the Implant's Thread Design Play a Role?
PMID:34360630
2021this review onlynot statednot extracted yet
Valente et al. (2021)
Collagen Fibres Orientation in the Bone Matrix around Dental Implants: Does the Implant’s Thread Design Play a Role?
DOI:10.3390/ijms22157860
2021this review onlynot statednot extracted yet
Wang 2020
Flame-sprayed strontium- and magnesium-doped hydroxyapatite on titanium implants for osseointegration enhancement
DOI:10.1016/j.surfcoat.2020.125452
2020this review onlyUpregulation of pro-osteogenic markers (RUNX2)not extracted yet
Wang 2021a
Potential biomarkers of abnormal osseointegration of implants in type II diabetes mellitus.
PMID:34794414
2021this review onlynot statednot extracted yet
Wang 2021b
Expression Level and Clinical Significance of Inflammatory Cytokines and Biochemical Markers in Gingival Crevicular Fluid During Different…
PMID:34397028
2021this review onlynot statednot extracted yet
Wang et al. (2021a)
matched by author and year (probable)
NRthis review onlynot statednot extracted yet
Wang et al. (2021b)
matched by author and year (probable)
NRthis review onlynot statednot extracted yet
Wu 2021
Melatonin prevents peri‑implantitis via suppression of TLR4/NF-κB.
PMID:34271168
2021this review onlynot statednot extracted yet
Wu et al. (2021)
Melatonin prevents peri‑implantitis via suppression of TLR4/NF-κB
DOI:10.1016/j.actbio.2021.07.017
2021this review onlynot statednot extracted yet
Zhang 2021a
Mechanical properties and osteoblast proliferation of complex porous dental implants filled with magnesium alloy based on 3D printing.
PMID:32915665
2021this review onlynot statednot extracted yet
Zhang 2023a
Improving the osseointegration and soft tissue sealing of zirconia ceramics by the incorporation of akermanite via sol infiltration for…
PMID:37115523
2023this review onlynot statednot extracted yet
Zhang et al. (2021a)
matched by author and year (probable)
NRthis review onlynot statednot extracted yet
Zhang et al. (2023a)
matched by author and year (probable)
NRthis review onlynot statednot extracted yet

Overlap with other reviews

Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.

Review question

ElementPlanned (methods)Found (results)
PopulationIn vitro (cell lines, organoids), in vivo (animal models) and human studies related to dental implant osseointegrationIn vitro, animal and human studies (n=32 studies)
InterventionAssessment of gene expression patterns, biomarkers or molecular signaling pathways towards osseointegrationGene expression biomarkers and signaling pathways; implant surface modifications
ComparisonBaseline or traditional understanding of osseointegration vs new technologies such as surface modificationsControl or traditional implant surfaces
OutcomesMarkers of successful osseointegration (e.g. RUNX2 upregulation) or implant failure (inflammatory cytokines, RANKL/OPG imbalance)RUNX2 and other pro-osteogenic markers; pro-inflammatory cytokines (IL-1b, IL-6, TNF-a); RANKL/OPG ratio; signaling pathways (NF-kB, Wnt)
Study designsPrimary research: in vitro, in vivo animal, prospective/retrospective clinical studies, January 2020 to May 2025, EnglishIn vitro, animal and clinical studies (n=32); meta-analysis of 4 in vitro studies
TimingNot specifiedNot specified