Aseptic-avascular osteonecrosis: local “silent inflammation” in the jawbone and RANTES/CCL5 overexpression

Abstract

Of the definitions listed in the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10), two disease descriptions can be found together: “idiopathic aseptic bone necrosis” and “avascular bone necrosis.” The relevant literature on both the conditions abbreviates both as “aseptic ischemic osteonecrosis in the jawbone” (AIOJ). To shed light on the clinical details of this condition, osteolytic jawbone samples of 24 patients with different systemic immunological diseases were examined using four steps: presurgical dental X-ray, postsurgical histology, polymerase chain reaction DNA analysis (PCR DNA) of bacteria, and RANTES/CCL5 (R/C) expression. These four steps showed that neither X-ray nor histology delivered unambiguous results with respect to inflammatory processes; furthermore, the PCR results did not show evidence of any microbial load within the jaw samples. However, there is a striking, coherent overexpression of chemokine R/C in the AIOJ samples. This study proved the aseptic existence of “silent inflammation” within the jawbone. The ICD-10 (AIOJ) definition, which is hard to interpret, can now be substantiated with clinical evidence, while the cytokine expressions described in this report can explain the systemic immunological effects observed within the group of examined patients.

Osteoimmunology of tumor necrosis factor-alpha, IL-6, and RANTES/CCL5: a review of known and poorly understood inflammatory patterns in osteonecrosis

“…Bacterial events, which are usually associated with high levels of TNF-α and IL-6 expression, could be ruled out within the FDOJ area. 60 Thus, R/C overexpression alone is involved in the characteristic and bone-degrading element of an FDOJ. TNF-α and IL-6 signaling in all other bone resorptive processes are excluded ( Figure 10 ).…”

<p>Ultrasound Sonography to Detect Focal Osteoporotic Jawbone Marrow Defects: Clinical Comparative Study with Corresponding Hounsfield Units and RANTES/CCL5 Expression</p>

“…The authors examined in detail the tissue in such jaw lesions that appears as fatty lumps inside an intact cortical bone. 6,7 They showed that the fatty lumps found are biochemically extremely active and produce certain cytokines in large quantities, in particular the chemokine RANTES/CCL-5 (R/ C). The expression levels of these cytokines are also elevated in a number of systemic diseases such as cancer, dementia, multiple sclerosis or arthritis.…”

“…However, in most of these cases, the local effect of neuralgic pain is missing. 6,7,21,22 It has also been plausibly shown that AIOJ/BMD/FDOJ describes the pathological condition of the jawbone, which is listed in code M87.0 of the ICD-10 (International Code of Diseases, Tenth Revision (ICD-10)). Figure 7 on the right shows the typical fatty-degenerative morphology of a BMD/AIOJ/FDOJ sample.…”

“…4 For the first time, the authors recommend the use of an ultrasound device 5 to detect these lesions. With respect to the conspicuous morphology, we proposed the term "fatty-degenerative osteonecrosis/osteolysis of jawbone" (FDOJ) for this cavitational osteonecrosis, 6,7 additionally to the term of AIOJ. According to publications by AI-Nawas, the status of the cancellous jawbone is of utmost importance for the success of dental implants.…”

CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

“…Abnormal immune response, imbalanced immune cell subpopulations, and higher plasma levels of inflammatory cytokines in patients with osteonecrosis suggest that inflammation plays a crucial role in this disorder [ 12 – 14 ]. Moreover, chemokines and cytokines released by necrotic cells recruit inflammatory cells, inducing local and systemic immune response in patients with osteonecrosis [ 15 – 17 ]. However, whether these inflammatory processes are also involved in SCD osteonecrosis has rarely been investigated.…”