Next-generation anticancer treatments: what impact on osseointegration?

The advent of modern systemic therapies — immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents — has radically transformed the prognosis of solid and haematological cancers. With the prolongation of survival, the demand for oral rehabilitation using dental implants is becoming a daily issue for the implantologist. However, these molecules interfere with the fundamental pillars of oral surgery: angiogenesis, immune regulation and bone remodelling. The practitioner is faced with a therapeutic void: how to manage implant placement in a patient undergoing targeted therapy?

This systematic review, conducted in accordance with the PRISMA 2020 protocols (PROSPERO CRD420251142681), aimed to precisely assess the clinical outcomes and implant complications reported in patients receiving these new treatments. The objective was to synthesise the available data to identify specific risks, such as early failure or implant-associated osteonecrosis of the jaw (MRONJ). By analysing seven recent case reports (2017–2024), the authors tested the hypothesis that these agents could negatively modulate the peri-implant tissue response, thereby laying the foundations for a risk stratification necessary for safe multidisciplinary management.

Systematic review methodology

This systematic review was conducted according to the PRISMA 2020 guidelines and registered in the PROSPERO database (CRD420251142681). The objective was to synthesise clinical data regarding dental implant outcomes in patients treated with novel systemic oncological therapies.

The search protocol targeted English-language publications on PubMed/MEDLINE, Scopus, ScienceDirect and the Cochrane Library. Inclusion criteria focused on patients receiving:

• Immune checkpoint inhibitors (ICIs);
• Tyrosine kinase inhibitors (TKIs);
• Anti-angiogenic agents.

Study selection, data extraction and quality assessment were performed independently by two reviewers. The quality of evidence was assessed using the Joanna Briggs Institute (JBI) checklist for case reports. A total of 7 case reports published between 2017 and 2024 were included, representing level IV evidence. The authors analysed implant complications, including early failure and medication-related osteonecrosis of the jaw (MRONJ), according to the type of systemic treatment administered.

Results of the systematic review

The authors of this review included 7 case reports published between 2017 and 2024, representing level IV evidence. The analysis highlights a clear dichotomy in clinical outcomes according to the therapeutic class administered during implant rehabilitation.

The compiled data indicate that the most severe complications, notably medication-related osteonecrosis of the jaw (MRONJ) and early implant failures, are predominant in patients receiving anti-angiogenic agents. These complications have been observed whether the agent is administered alone or in combination with immune checkpoint inhibitors (ICIs) and antiresorptive agents.

Qualitatively, the reported observations highlight the following points:

• Functional morbidity: Failures associated with anti-angiogenic therapies have resulted in significant morbidity for patients.
• Need for interventions: Cases of MRONJ and failures often required invasive surgical interventions to be resolved.
• Inflammatory synergy: The authors suggest that ICIs could potentiate inflammatory bone loss, particularly when combined with anti-VEGF agents.
• Uncertainty regarding ICIs: The specific role of ICIs as monotherapy remains undetermined due to the scarcity of isolated clinical data.

Conversely, the two documented cases involving TKIs show that these molecules appear to be compatible with stable osseointegration in patients whose systemic condition is controlled. No p-value is reported in this review due to the descriptive nature of the included case studies.

Clinical analysis and impact on osseointegration

The results of this systematic review highlight a striking disparity between the different classes of targeted therapies. While tyrosine kinase inhibitors (TKIs) appear compatible with successful osseointegration in stable patients, anti-angiogenic agents prove to be significantly more problematic. In the reported cases, the latter are consistently associated with early failures and osteonecrosis of the jaw (MRONJ), particularly when combined with antiresorptive agents or immune checkpoint inhibitors (ICIs).

Study limitations and state of knowledge

The interpretation of these data must remain cautious: the study relies exclusively on seven case reports (level of evidence IV), which constitutes a weak statistical foundation. The specific role of ICIs in monotherapy remains uncertain due to a lack of sufficient data. Unlike better-documented conventional chemotherapy protocols, the impact of these new therapies on bone remodelling and peri-implant angiogenesis still lacks long-term clinical follow-up.

Implications for the practice

For the implantologist, this study requires rigorous risk stratification. Implant placement in a patient on active anti-VEGF therapy must be approached with extreme caution, given the observed risk of severe functional morbidity. Close coordination with the oncologist is essential to evaluate the surgical timing, as TKIs appear, pending confirmation, to be less detrimental to bone anchorage than therapies directly targeting vascularisation.

Summary of results

This systematic review of 7 case reports (2017-2024) highlights an increased risk of implant complications, notably early failures and MRONJ, in patients receiving anti-angiogenic agents, particularly in combination with ICIs or antiresorptive agents. Conversely, tyrosine kinase inhibitors (TKIs) demonstrated favourable osseointegration outcomes in the two documented cases, whereas the specific impact of ICIs as monotherapy remains undetermined.

In practical terms, for the practitioner:

• Major caution with anti-VEGF: Avoid or postpone elective implant placement during active anti-angiogenic therapy, as the risk of necrosis and functional morbidity is high.
• Vigilance regarding dual therapies: Be particularly vigilant with patients combining ICIs and anti-angiogenic or antiresorptive agents, a combination that appears to promote inflammatory bone loss.
• Oncological coordination: Systematically involve the oncologist in your therapeutic decision-making to assess the patient's stability and validate a safe intervention window prior to any implant surgery.

Technical glossary

Immune checkpoint inhibitors (ICIs): Monoclonal therapies that reactivate the antitumour immune response, but can induce inflammatory bone processes.

Tyrosine kinase inhibitors (TKIs): Molecules targeting specific enzymes involved in tumour growth; limited data suggest a relative compatibility with osseointegration.

Anti-angiogenic agents (Anti-VEGF): Medications (e.g. bevacizumab) blocking the formation of new blood vessels, essential for peri-implant bone healing.

MRONJ (Medication-Related Osteonecrosis of the Jaw): Medication-related osteonecrosis of the jaw, characterised by persistent bone exposure, here associated with anti-angiogenics.

PRISMA 2020: Standardised reporting protocol ensuring transparency and methodological rigour of systematic reviews.

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