The clinical significance of "neuralgia inducing cavitational osteonecrosis" (NICO), or cavitational osteopathosis, has been called into question. Dodes and Schissel (2000) reviewed the history of this syndrome. They explained that the American Academy of Biological Dentistry and other proponents of NICO claim that facial pain is caused by infected "cavities" within the jawbones. In addition, some proponents claim they can cure such conditions as arthritis, heart disease, and pain throughout the body by removing these infected cavities from the patient's jawbones. Unlike abscesses, cysts, or periapical lesions, these cavities are not apparent on x-ray films, but are only purportedly detectable with an ultrasonograph bone densitometer.

Proponents claim that these infected cavities are not treatable with antibiotics, but the infection must be cured by surgically scraping them out. Some practitioners have advocated rinsing the "cavity" with colloidal silver and administering chelation therapy and intravenous vitamin C. Some proponents of biological dentistry have claimed that root-canal-treated teeth cause NICO as well as a host of other chronic systemic diseases. These proponents remove all root-canal-treated teeth and most of the vital teeth close to the area where they say an infection exists. As a result, patients have had healthy teeth removed without any improvement in their diseases.

Dodes and Schissel (2000) concluded, however, that there is no scientific evidence to support these assertions or the diagnostic and treatment methods based on them. The prime promoter of NICO is J.E. Bouquot, D.D.S., M.S.D., a West Virginia oral pathologist who coined the term in the 1980s. Dodes and Schissel reported that several oral pathologists who blindly reviewed the same tissue blocks that Dr. Bouquot had diagnosed as having NICO judged the tissue to be entirely normal.

The Food and Drug Administration-cleared labeling on one device used to assist in diagnosing NICO or NICO-type conditions states that the clinical significance of the images is unknown. The indications section of the product labeling contains the following statement: "The clinical significance and correlation of the [device’s] images, including column height and color grading, has not been established for specific osseous pathology, or normal bone. Positive images represent alveolar regions that attenuate ultrasound signals."

An ultrasonograph bone densitometer purportedly detects and precisely images porosity of the bone to aid medical professionals in diagnosing bone marrow edema syndrome, NICO, osteomyelitis and periodontal pockets of the buccal bone. However, there are no articles on the effectiveness of the device published in peer-reviewed medical journals. The manufacturer cites a number of abstracts in support of the effectiveness of the device. However, abstracts do not undergo the detailed peer review that is required for publication of an article in a quality peer-reviewed medical journal. Furthermore, the abstracts provide insufficient description of study methodology to allow one to draw conclusions about the validity of the results. For example, the abstracts fail to provide sufficient detail about how subjects for study were selected, inadequate description of the gold standard, whether the investigators were blinded to results of competing studies, and whether the results of the ultrasonography improved outcomes.

In a series of articles reviewing unconventional dental practices and products published in the Journal of the Canadian Dental Association, Goldstein and Epstein (2000) stated that "papers supporting 'scientific' aspects of NICO have been published in peer-reviewed mainstream journals. The publications offer changing explanations with only anecdotal case reports and no definitive etiology, biochemistry, histopathology, neuropathology or diagnosable clinical features meeting scientific standards of proof, while advocating repeated surgical procedures for diagnosis and therapy, also without proof of effectiveness. At present, the existence of NICO as a clinical entity remains unproven and unaccepted by the majority of science-based practitioners. NICO must be evaluated by well-designed studies; until then, unproven concepts should not be the basis for invasive dental surgical procedures".

Sciubba (2009) stated that NICO remains controversial several years following the initial description. Changing etiologic concepts have led to confusion as well as the significant departures from the concept first defined by Ratner, which served as the basis for the explaining the pain syndrome with features of trigeminal neuralgia. Since the earliest publications on the subject by Bouquot et al, there have been many challenges and counter-claims to the concept introduced. The author noted that absence of any form of research design and approval by institutional review panels remains a weakness in terms of acceptance of the information provided in the literature said to support the stated etiology of this entity.

Glueck et al (2010) hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with NICO. In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction; and 2 healthy normal control subjects were matched per case by race and gender. Homozygosity for the mutant eNOS allele was present in 6 out of 22 patients (27 %) with NICO compared with 0 out of 44 (0 %) race- and gender-matched control subjects; heterozygosity was present in 8 patients (36 %) versus 15 control subjects (34 %); and the wild-type normal genotype was present in 9 patients (36 %) versus 29 controls (66 %) (p = 0.0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45 %]) than in control subjects (15 out of 88 [17 %]) (p = 0.0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (p = 0.13). The authors concluded that the eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.

Klassner and Epstein (2011) reviewed the literature for NICO, and stated that "the etiology, pathogenesis and treatment of NICO are speculative and not well defined, and the reported bone changes may represent variations of normal changes. As a result, one can argue that the symptoms of chronic pain attributed to NICO are better explained by established concepts of neuropathic pain; thus, they should be approached medically and not managed surgically." The authors concluded: "Without a confirmed clinical diagnosis of localized bone pathosis, aggressive and invasive procedures are not warranted. Such interventions may have no effect or may even worsen the pain by increasing sensitization of the central nervous system."

In a position statement, the American Association of Endodontists (AAE, 2012) has stated that the association "cannot condone surgical interventions intended to treat suspected NICO lesions.... In addition, the practice of recommending the extraction of endodontically treated teeth for the prevention of NICO, or any other disease, is unethical and should be reported immediately to the appropriate state board of dentistry."

In a systematic review, Sekundo and colleagues (2021) examined the etiologic factors, proposed diagnostic means and treatment strategies for NICO. These investigators carried out a search of the literature published up to June 2020 using Medline, the Cochrane Library, PsycINFO, CINAHL and Web of Science. The scientific quality of the evidence was rated according to NIH Quality Assessment Tools. A total of 4,051 articles were found, 59 were reviewed in full text, and 29 studies were included. With the exception of hereditary coagulopathies, which were identified as potential risk factors in 5 studies, suggestions concerning the etiology varied widely. No gold standard diagnostic mean could be identified. Treatment was most often performed by surgical curettage of the affected bone. Surgical treatment outcomes were equally varied: significant facial pain remission was reported in 66 % to 100 % for periods varying between 2 months to 18 years, whereas no or little relief and recurrences were reported in up to 1/3 of cases. All studies were observational in their design. All investigations were rated as poor quality because of high risk of bias and non-transparent reporting. The authors concluded that the evidence concerning the etiology, diagnosis and treatment of NICO is poor. They stated that prospective diagnostic and therapeutic studies are needed before the usefulness of invasive therapeutic procedures can be evaluated.

Scope of Policy

This Clinical Policy Bulletin addresses neuralgia inducing cavitational osteonecrosis (NICO) and ultrasonograph bone densitometer to detect NICO .

Experimental and Investigational

Aetna considers surgery (including scraping of "infected cavities" and removal of root-canal-treated teeth) and/or any other therapies (e.g., rinsing the "cavity" with colloidal silver and administering chelation therapy and intravenous vitamin C) and bone graft replacement for the treatment of neuralgia inducing cavitational osteonecrosis (NICO)-related diagnoses to be experimental and investigational because the clinical significance of this syndrome is in question.

Aetna considers the use of devices to image the jawbones to diagnose NICO or NICO-type conditions experimental and investigational because there is no adequate scientific evidence to support their clinical value.