Susan W. Herring, Ph.D., University of Washington, Seattle, WA

• Stephen Feinberg, Ph.D., D.D.S. M.S., University of Michigan Medical Center, Ann Arbor, MI
• Stephen B. Milam, D.D.S., Ph.D. University of Texas Health Science Center, San Antonio, TX
• Randall Wilk, D.D.S., Ph.D., M.D., Louisiana State University, LA

• David E. Altobelli, D.M.D., M.D., DEKA Research and Development, Manchester, NH
• Thomas F. Budinger, M.D., Ph.D., University of California, Berkeley, CA
• Stephen L. Gordon, Ph.D., Cognate Therapeutics, Bethesda, MD
• John Watson, Ph.D., University of California San Diego, La Jolla, CA
• Jon-Kar Zubieta, M.D., Ph.D., University of Michigan, Ann Arbor, MI

1. Currently available non-invasive imaging technologies (CT 3D X-ray, micro CT, PET, SPECT, MRI, fMRI, MRS, and thermography) should be utilized to establish, validate, and standardize the clinical diagnostic criteria to assess the etiology and mechanisms of chronic pain and dysfunction in TMJ Disorders.

2. Studies should integrate interdisciplinary experts related to structure, mechanical function, metabolism, blood flow of bone, joints, muscle, central and peripheral neural pathways, and the endocrine, paracrine, cytokine factors that impact upon these craniofacial structures that could be expected to be the underlying cause of such pain and jaw dysfunction.

3. A cohort database should be developed to assess “risk” for TMJ disorders in subjects that present with pain in the TM region (from mild to severe), together with normal subjects that have not yet exhibited any clinical manifestations of TMJ dysfunction. Protocols should be developed which include self-reported health status, as well as physical examinations by experts in medical sub-specialties to diagnose co-morbid conditions and overall health status of the TMJ patients.

4. Prospective longitudinal studies of the most vulnerable population are needed to establish where on the distribution-time curve intervention and therapy is recommended and at what point associated risk factors and co-morbid conditions emerge.

5. Genetic linkage studies should be carried out to map the phenotypes defined by the standardized imaging strategies and other related phenotypes that are considered to be likely determinants of the pain associated with TMJ disorders. Efforts should be made to reduce population heterogeneity in order to increase the statistical power of these studies. Subjects should be screened using standardized methodologies described above.

6. Novel therapeutic approaches should be developed that will provide “joint assistance” to improve range of motion and reduce the pain of joint motion and for “joint replacement” as required.

7. Methods to expedite the transfer of this information to all health care disciplines should be developed.

The Third Scientific Meeting of the TMJ Association was stimulated by the critical need to establish improved research and diagnostic criteria for temporomandibular Diseases and Disorders. Clinicians and scientists interested in studying these conditions have been handicapped by an absence of standardized and accepted diagnostic criteria. It was the goal of the organizers to bring basic and clinical scientists from a number of disciplines together with experts in physics, bioengineering, bioimaging, computational biology, and modeling to assess the challenges currently faced, and explore novel methods to define TMJ-vulnerable populations. It was also the goal to stimulate interest among young investigators in a multidisciplinary approach to research on TMJ diseases and disorders.

The majority of the support for the meeting was obtained from five agencies of the National Institutes of Health following submission and competitive peer review of an R13 meeting grant. These agencies included the National Institute of Dental and Craniofacial Research, the Office of Rare Diseases, the National Institute of Biomedical Imaging and Bioengineering, the Office of Research on Women’s Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. These resources were supplemented by individual patient and family donations and student travel support by the Whitaker Foundation.

1. Continued NIH support of TMJA Scientific Meetings.

2. Biomechanics to biology: Further studies are needed that advance the characterization of the biomechanics of the TM joint and muscle in order to utilize these approaches for diagnosis and predictions of pathology. Cowley commented that this work should include the derivation of patient- specific anatomically based computational models (such as finite element analysis) that include structures of the bone and fibrous tissue, neuromuscular units, metabolism and blood supply, and sensory and motor regions of the CNS that are related to the craniofacial structures. Experimental and clinical validation of these models will be required, utilizing imaging technologies such as fast CT 3D X-ray), micro CT, PET MRI, fMRI, MRS, thermography and any other non-invasive technologies that can capture the required data).

3. In light of the evidence that TMJ is a multifactorial disease, population studies will be required to determine its genetic and environmental etiology. It is recommended that efforts be made to build a uniform infrastructure to recruit and phenotype a broad spectrum of subjects from normal to severely diseased. It was recommended (Cowley) that standardization of affordable phenotyping methodologies and technologies will be imperative to advance these efforts.

4. It is recommended that new clinical criteria for defining TMJ diseases and disorders, given the current availability of remarkably fast and sensitive imaging technologies that can now be applied to study the craniofacial and neural structures as demonstrated at this meeting. This need was greatly expanded upon in many discussions throughout the meeting; imaging of joint-muscle-blood flow-O2-inflammation; study the structures during active motion; longitudinal studies, etc. Establish where on the distribution-time curve intervention is recommended and at what point associated risk factors emerge.

1. Recommends studies to determine if routinely carried out body scans using FDF PET techniques (for diagnosis of tumors) could be used for detection of jaw muscle (e.g., pterygoid) metabolic activity (e.g., stress) i.e., TMJ-bone/joint stress.

2. Recommendations were made to begin by mining the data (whole body scans) already available at many institutions to obtain preliminary data, and then designing prospective studies using routine PET scans that would be extended to routinely include the head and neck regions. (He believes these could be done at a cost of only about $450 per person).

3. Recommendations were made to determine if high resolution 18F (ionic) PET techniques can be used to characterized changes in TM bone blood flow.

1. Recommended utilizing both imaging techniques and chemical markers to determine the mechanisms behind the pain in TMJ and the relationship of pain in the TM joints and muscles to other body pain.

2. Recommended studies to determine the biological basis of TMJ pain and the relationship of pain to the ongoing bone and soft tissue destruction (e.g., cytokine and TNF-alpha focus) in order to predict future destruction of the TM joints.

3. It was recommended (Milam) that nanoparticle technology be utilized to image local regions of inflammation that would be related to these cytokine responses and also the use of “pinpoint” fluorescent or isotopic techniques (Budinger) to image inflammatory regions in joints just as they are used to detect vascular plaques.

4. Prospective studies based on the above strategies were proposed that would provide targets for early diagnosis and treatment.

1. Recommended that fMRI and PET scanning techniques be utilized to evaluate the complex neurobiological pathways in both normal and TMJ disease states.

2. Recommendations were made to study the risk for TMJ disease in normal subjects who have not exhibited any clinical manifestations of TMJ dysfunction (prospective longitudinal studies of the most vulnerable population such as young Caucasian women).

3. Recommendations were made to screen disease subjects using these technologies in order to stratify them for more extensive phenotyping and genotyping studies.

1. Recommended development of a registry for TM joint- and muscle-related animal model systems, which could be used to elucidate human joint problems. These would include knockout models or animals that over express genes related to TM tissues and functional pathways.

2. Recommended adding TMJ phenotyping to genetic population studies that are currently established in order to utilize the broad array of already available phenotypes to provide considerable added value to the mapping and identification of polymorphisms related to TMJ diseases.

1. Recommended that new algorithms and diagnostic approaches be used to establish a classification system and framework of understanding and treatment of TMJ diseases.

2. Recommendations were made to make available current imaging and diagnostic tools for use by “frontline” dentists and physicians to define the stages of disease development for the early diagnosis and treatment of the disease.

3. Recommended that the NIH support the development of a centralized national patient database where this information could be correlated and mined to establish the algorithms for diagnosis and treatment.

1. Recommended development of a virtual reality model of TMJ (anatomy, kinematic studies, and biomechanics) that could be utilized for teaching, research and treatment.

2. Recommended improved education in dental and medical schools.

3. Recommended recruitment of clinicians (MDs) in studies involving technical advances.

1. Recommended that imaging parameters be established for different stages of the disease.

2. Recommended imaging techniques not only for diagnosis but for outcome analysis of specific interventions.

John Watson, PhD

1. Recommended that studies be supported to develop algorithms to better quantify and define the understanding of joint motion and mechanics (“equations of motion” of the TMJ).

2. Recommended utilization of thermal imaging technologies to define inflammation in craniofacial structures and systemic regions of the body.

3. Recommended the development of more affordable approaches of biological imaging (for material properties, mechanics, inflammation and other diagnostics) in order to obtain special, quantitative characteristics of the joints and muscles.

4. Recommended that imaging modalities and longitudinal studies using X-ray techniques be designed to reduce radiation doses by 80 percent.

5. Proposed a 10-year prospective study in which the difficulty and cost of various diagnostic approaches be compared to determine what is predictive of TMJ disorders.

6. Recommended the use of R21 exploratory grants.

7. Recommended an annual research-wide meeting of clinicians, grantees, contractors, and patients