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

EPMA Journal https://doi.org/10.1007/s13167-018-0138-6 RESEARCH Titanium implants and silent inflammation in jawbone—a critical interplay of dissolved titanium particles and cytokines TNF-α and RANTES/CCL5 on overall health? Johann Lechner 1 & Sammy Noumbissi 2 & Volker von Baehr 3 Received: 29 March 2018 / Accepted: 16 May 2018 # The Author(s) 2018 Abstract 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. Results 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. Discussion 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. Conclusion 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. Keywords Dental titanium implants . TNF-α . RANTES/CCL5 . Fatty degenerative osteonecrosis of the jawbone . Immune system disorders . Silent inflammation . Preventive medicine * Johann Lechner 1 Clinic for Integrative Dentistry, Grünwalder Str. 10A, Munich, Germany 2 Miles of Smiles Implant Dentistry, 801 Wayne Ave no. G200, Silver Spring, USA 3 Institute for Medical Diagnostics in MVZ GbR, Nicolaistr. 22, 12247 Berlin, Germany Abbreviations CFS Chronic fatigue syndrome CI Chronic inflammation FDOJ Fatty degenerative osteonecrosis of the jaw F D O J - T -Fatty degenerative osteonecrosis of the jaw adjaIMP cent to a titanium implant HJB Healthy jawbone ISD Immune system disorders MS Multiple sclerosis OvC Ovarian cancer EPMA Journal PPPM R/C RA TAU TI T-IMP TNF-α TrN Predictive Preventive Personalized Medicine RANTES/CCL5 Rheumatic arthritis Transalveolar ultrasound technology Titanium Titanium implant Tumor necrosis factor-alpha Atypical facial pain/trigeminal neuralgia role of cytokines in areas of FDOJ surrounding implants in a cohort of patients with immune system disorders (ISD). We propose the following hypothesis: T-IMPs may be a possible contributor to the development of CI of the jawbone extending beyond the local condition of peri-implantitis. Individuals with specific risk factors may be more susceptible to subsequently developing certain types of systemic diseases (i.e., ISD). Background Material and methods Tooth replacement is a long-sought-after and practiced solution in dentistry. In modern dentistry, one of the most established and proven methods is the replacement of lost or missing teeth with dental implants. The most popular and proven implant materials are titanium and titanium alloys which have shown to be very successful in terms of their integration with surrounding tissue. However, removal of the tooth and subsequent implantation submit the jawbone and body to an inflammatory process that, in most cases, leads to uneventful healing and implant stability. Multiple investigators have found that titanium implants can induce inflammation in the surrounding tissue over time, leading to the expression of certain mediators known to cause local and systemic health problems. While acute disease is unavoidable, chronic diseases (cancer, autoimmune diseases, etc.) are the clinical and visible manifestations of a constantly stimulated immune system [1–4]. These triggers lead to the activation of signaling pathways which favor a predisposition to the development of chronic disease. In general, cell communication systems are organized as cascades with sequenced stages [5]. Signaling messengers like cytokines carry instructions and are received by those cells with specific receptors which are able to recognize them. In earlier publications, we defined this chronic inflammatory process as fatty degenerative osteonecrosis in the medullary spaces of the jawbone (FDOJ) [6, 7]. Peri-implant pathology also commonly known as “peri-implantitis” is a widely discussed phenomenon based on immunological susceptibility to TI and macrophage reaction which can ultimately lead to titanium implant (T-IMP) failure [1, 8, 9]. In daily dental practice, the effects of implants on overall health are often overlooked because local problems appear to resolve after the implants are healed and integrated. Objectives This research aims to elucidate the transition from acute trauma during the insertion of dental implants to chronic inflammation (CI) of the jawbone. Herein, we attempt to define the Groups of patients examined Patients with T-IMP (n = 14) were selected. This T-IMP group consisted of patients with well-osseointegrated T-IMPs and with clinical symptoms of ISD diagnosed by internal medicine physicians with the following ISD as inclusion criteria: rheumatic arthritis (RA) = 7, neurodegenerative diseases characterized by a progressive loss of neuron function including chronic fatigue syndrome (CFS) and multiple sclerosis (MS) = 3, ovarian cancer (OvC) = 1, and atypical facial pain/trigeminal neuralgia (TrN) = 3. A second mandatory inclusion criterion for the T-IMP group was local diagnosis of FDOJ (...truncated)