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EPMA J. 2018 Jun 8;9(3):331-343. doi: 10.1007/s13167-018-0138-6. eCollection 2018 Sep.

Titanium implants and silent inflammation in jawbone-a critical interplay of dissolved titanium particles and cytokines TNF-α and RANTES/CCL5 on overall health?

Author information

Clinic for Integrative Dentistry, Grünwalder Str. 10A, Munich, Germany.
Miles of Smiles Implant Dentistry, 801 Wayne Ave no. G200, Silver Spring, USA.
Institute for Medical Diagnostics in MVZ GbR, Nicolaistr. 22, 12247 Berlin, Germany.


Background and introduction:

It is a well-known fact that titanium particles deriving from dental titanium implants (DTI) dissolve into the surrounding bone. Although titanium (TI) is regarded as a compatible implant material, increasing concern is coming up that the dissolved titanium particles induce inflammatory reactions around the implant. Specifically, the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) is expressed in the adjacent bone. The transition from TNF-α-induced local inflammation following insertion of DTI surgery to a chronic stage of "silent inflammation" could be a neglected cause of unexplained medical conditions.

Material and methods:

The signaling pathways involved in the induction of cytokine release were analyzed by multiplex analysis. We examined samples of jawbone (JB) for seven cytokines in two groups: specimens from 14 patients were analyzed in areas of DTI for particle-mediated release of cytokines. Each of the adjacent to DTI tissue samples showed clinically fatty degenerated and osteonecrotic medullary changes in the JB (FDOJ). Specimens from 19 patients were of healthy JB. In five cases, we measured the concentration of dissolved Ti particles by spectrometry.


All DTI-FDOJ samples showed RANTES/CCL5 (R/C) as the only extremely overexpressed cytokine. DTI-FDOJ cohort showed a 30-fold mean overexpression of R/C as compared with a control cohort of 19 healthy JB samples. Concentration of dissolved Ti particles in DTI-FDOJ was 30-fold higher than an estimated maximum of 1.000 μg/kg.


As R/C is discussed in the literature as a possible contributor to inflammatory diseases, the here-presented research examines the question of whether common DTI may provoke the development of chronic inflammation in the jawbone in an impaired state of healing. Such changes in areas of the JB may lead to hyperactivated signaling pathways of TNF-α induced R/C overexpression, and result in unrecognized sources of silent inflammation. This may contribute to disease patterns like rheumatic arthritis, multiple sclerosis, and other systemic-inflammatory diseases, which is widely discussed in scientific papers.


From a systemic perspective, we recommend that more attention be paid to the cytokine cross-talk that is provoked by dissolved Ti particles from DTI in medicine and dentistry. This may contribute to further development of personalized strategies in preventive medicine.


Dental titanium implants; Fatty degenerative osteonecrosis of the jawbone; Immune system disorders; Preventive medicine; RANTES/CCL5; Silent inflammation; TNF-α

Conflict of interest statement

The authors declare that they have no competing interests.Not applicable.All the patients were informed about the purposes of the study and consequently have signed their “consent of the patient.” All investigations conformed to the principles outlined in the Declaration of Helsinki and were performed with permission by the responsible Ethics Committee of IMD-Berlin forensic accredited Institute DIN EN 15189/DIN EN 17025. This article does not contain any studies with animals performed by any of the authors.

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