TMJ Bioengineering Conference - Boulder Colorado May 25-27, 2006 Presentation by Terrie Cowley, President of The TMJ Association

Transcription

1 TMJ Bioengineering Conference - Boulder Colorado May 25-27, 2006 Presentation by Terrie Cowley, President of The TMJ Association Let me congratulate Michael Detamore, Kerry Athanasiou and Jeremy Mao for organizing a scientific meeting on temporomandibular diseases and disorders. Speaking for TMJ patients, we are grateful that well-respected scientists are turning their attention to a joint which has long deserved scientific scrutiny, but which it has long lacked. Bringing new players to the field is so important and we commend the organizers for inviting researchers who may be naïve to the complexities of the temporomandibular joint and its problems. The organizers of this meeting have asked me to do three things. Provide background information and history, identify the problems and provide directives. Let me begin with background. As you no doubt know, the temporomandibular joints are the two joints which enable the jaw to move up and down, side to side and forward and backward under the control of a complex set of muscles. The combination of hinge and sliding motions allowing 3-dimensional movements, and the fact that these joints are co-dependent make the TM joints among the most complex in the body. The joints, located at the base of the skull, are situated amidst the most sensitive and vulnerable areas of the head, at the convergence of the body s major cardiovascular, neurological, auditory and ocular systems. In 1996, the National Institutes of Health defined temporomandibular disorders as a collection of medical and dental conditions affecting the temporomandibular joint and/or the muscles of mastication, as well as contiguous tissue components. While conditions such as degenerative arthritis and trauma underlie some joint problems, for the most part TMJ diseases and disorders comprise a heterogeneous group with no common etiology. What the conditions have in common are pain and dysfunction of the jaw, but these, too, vary widely in extent and severity. Pain may be limited to the face or jaw joint area, but may include headaches and earaches, dizziness, masticatory musculature hypertrophy, limited mouth opening, inability to open or close the mouth, joint sounds and other complaints. The severity of pain can range from mild to intractable, and jaw dysfunction may range from a bite that feels off, to the need for a feeding tube for sustenance. 1

2 Interestingly, as information has accumulated in the past few years, it appears that many patients with temporomandibular disorders also exhibit co-morbidities associated with other body systems. Examples include chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, multiple chemical sensitivity/allergies, tension and migraine headaches, and a variety of cardiovascular symptoms including mitral valve prolapse and arrhythmias, and sleep disturbances. With the recognition of these co-morbidities, the TMJ problem is now being viewed as just one component of a multi-systems illness. As a result, TM diseases and disorders, once considered dental problems, are being recognized as a complex disease influenced by gender, genes, environmental and behavioral triggers. The epidemiological data for TMJ problems are all over the place we really don t have good incidence and prevalence figures of who is affected by TMJ problems. The lowest prevalence puts the number at over ten million people. One thing we do know is that overwhelmingly an estimated 90 percent of those seeking treatment -- are women in their childbearing years: teenagers through menopause. For the past 70 years there have been dozens of theories, philosophies and treatment programs for TMDs, essentially proposed by dentists. These theories mainly revolved around the occlusion, the position of the condyle, and ways to recapture the disc. In addition, there were many it s all in your head practitioners who attributed joint problems to psychological causes. The various theories and treatment regimens were, and I add, continue to be zealously promoted by what one editorial writer described as Hilton University TMJD seminars. He went on to write that in the early days most dentists believed TMJ to be related to medicine and most physicians believed it to be primarily a dental problem. It was a no man s land of diagnosis and treatment, a classic case of a condition that fell through the cracks, where it still lies. In 1989, Enid Neidle, then the scientific advisor to the American Dental Association, wrote, TMJ is the hottest area of unorthodoxy and out-and-out quackery. Seven years later not much had changed. Conclusions from the 1996 NIH-sponsored Technology Assessment Conference on Management of Temporomandibular Disorders were summarized by a Washington Post 2

3 reporter who wrote, and I ll paraphrase, the professionals don t know what pain in the jaw signifies, don t know what to call it, don t know who should treat it, don t know what works, and a lot of people s lives are being destroyed. In 2001, the Health Technology Assessment Information Service of ECRI (a non-profit health service research agency) and the Agency for Healthcare Research and Quality published reports on several TMJ treatments. These two studies confirmed the findings of the 1996 technology assessment conference and reinforced other reviews of the literature that decried the lack of large randomized clinical trials or other types of rigorous studies that could demonstrate the safety and efficacy of treatments for TMJ diseases and disorders. As well, there was no consensus regarding the etiology, course of disease, and even diagnostics of TMJDs. Today as many as 25 different types of practitioners, including general dentists, orthodontists, prosthodontists, oral surgeons, nutritionists, chiropractors, osteopaths, physical therapists, those who treat pain and psychologists treat TMJDs. It is said that the floor where you exit the elevator in a building determines the treatment you ll get. And what are these treatments? In 1994 there were 49 treatments being recommended to TMJ patients and hardly a month goes by when we don t hear of yet another new cure or gimmick. You will have gathered by this time that these treatments are mainly based on faith and anecdotes. You should also understand that many patients get better without treatment. What we don t know is how many patients are unaffected, improved or harmed by one or many of the treatments they receive or if in fact the placebo effect is responsible for the success of some treatments. What we do know is that TMJ patients are being treated in a system where no one professional takes responsibility for the patient a system in which an unbelievable number of referrals, with unscientific, unproven treatments, and hope, is sold to the patient by each referrer. One of the 50+ treatments is TMJ implants of varying kinds. A frequent problem with jaw joints is that the disc that serves as a cushion between the skull and the condyle tears or dislocates. One procedure to solve this problem has involved removal of the disc and replacing it with one composed of reinforced Silastic sheeting by Dow Corning, or Proplast-Teflon by the Vitek Company. These implants, no larger than a thumbnail, are manufactured individually or custom cut from sheets or blocks in the operating room by the surgeons and then sutured to the skull or condyle. Basically, Silicone products had been grandfathered into use in the jaw by the FDA 3

4 because they were on the market before the Safe Medical Devices Act was passed. The FDA also approved the Vitek Proplast-Teflon implant in 1983, saying it was substantially equivalent to the Silicone products. These devices lacked fundamental bioengineering and biocompatibility testing. Reports of failure of the Vitek implant began surfacing in 1984 and, amazingly, the scientific advisor to the company, following the removal of one of the implants, wrote to the manufacturer that they may have a calamity of unbelievable proportions on our hands. Nevertheless, he and the manufacturer continued to aggressively market the material and surgeons continued to implant it. In 1990, the FDA recalled the product because the implants ate away at bone and tissue; in some cases making a cavity which perforated the skull into the brain. The FDA called this, open communication to the brain. They also said that the device would fail 100% of the time. Several months after the recall the FDA seized all implants at Vitek. The founder and president moved the patents offshore, declared bankruptcy and fled the country leaving FDA to handle a class I recall for the first time in its history. When I asked an FDA official how this could happen he simply said, TMJ implants fell through the cracks here. When I asked what they were going to do about the Silastic implant, which we knew was also causing problems, he replied, There haven t been any studies on those, so we can t do anything. Silastic is still being used in TM joints off label. Implantation of autogenous and cadaver materials, such as ear or femur cartilage, temporalis muscle flap, rib grafts, fat grafts, etc. are common procedures but are relatively unsuccessful. Total joint devices made of various materials and whose components are screwed to the skull and mandible began to be aggressively marketed as the remedy to the joint destruction that had been caused by Silastic and Proplast-Teflon. Over one thousand people with these devices reported the various following problems to us: severe pain, facial deformity, infections, metalosis, extreme facial swelling, allergic reactions to the materials, the components cracking and/or breaking, a component breaking through the 4

5 middle ear, the skull, exiting the side of the face, screws coming loose, paralysis and numbness causing inability to swallow, make facial expressions and close one s eyes. Total joint devices, too, have had a catastrophic history at FDA. These devices remained unclassified until 1999 when PMA s were called for. Some devices were approved with woefully inadequate testing and clinical data. The Safety and Summary Statement Inclusion Criteria for one basically says that we don t know who this device will help but we are sure it will help someone. Another device went to the Dental Products Panel, received approval and three weeks later the FDA inspected the offices of one of the two implanting surgeons taking part in the study. They found violations which included failure to obtain signed consent documents, to conduct the study in accordance with the investigation plan, to maintain accurate and complete subject records and to use the IRB approved consent form for subjects. At least half of the subjects had to be dropped from the panel approved study. TMJ implants provide the perfect segue for me to explain my passion about this problem and why there is a TMJ Association. In 1980, a dentist determined that I had hypermobile jaw and he refused to even clean my teeth until my jaw was stabilized. Two years, four dentists, three splints, and two equilibration sessions later, surgery was recommended and I opted for it, thinking if it was done at an academic institution, it had to be OK. And if this was the only way I could get my teeth cleaned I had no choice. Before the operation the surgeon told me, You will never know you had a problem. You will be at work the day after surgery and the material we use is from Dow Corning, and they make the best cookware around. Two months later, enduring excruciating pain, and still unable to drive or work, I asked the surgeon if I was going to die, asked him what had gone wrong. He simply said, I don t know what s wrong with you, your joints are fine, when in fact the implants had already broken. I have never had a day since the surgery that I do not know I have a jaw problem. I am never without some degree of pain and, like the thousands of other implant patients we ve heard from, I continue to endure life-altering consequences of these implants. Four years after my surgery I met another TMJ patient and we instantly knew we had to do something about this. We formed a support group in Milwaukee which became The TMJ 5

6 Association. We interviewed everyone in town we knew who was treating the condition, read the literature and over the next four years with enlisted scientific expertise determined that there wasn t credible science behind what practitioners were doing. We also met many patients who were in far worse straits than we were. By 1990, we knew we had to change the quality and direction of TMJ research and demand that treatments be based in sound science. In 1991, I was so outraged over the Vitek disaster that I began to look to Congress for help. After visits to about 25 representatives and senators, in 1992, New York Congressman Ted Weiss held a hearing titled, Are FDA and NIH Ignoring the Dangers of FDA implants? The investigation revealed sordid details of the roles of manufacturers, oral surgeons, clinical scientists working with manufacturers, and the impotence of the FDA and NIH in what the Wall Street Journal, in their longest article to date, dubbed a medical mess. What ensued was a who s on first blame game with the FDA blaming the manufacturers, the manufacturers blaming the surgeons and patients and the surgeons blaming all of the above. No one was accountable, no one responsible. Following the congressional hearing, phone calls, letters and s began pouring in from across the country to the TMJA office located in a spare bedroom in our house. I networked with other TMJ patients, who were board members, across the country by phone and fax. Most implant patients told us that their skulls and condyles were degenerating. Many experienced repeated bouts of heterotopic bone growth, limiting their ability to open their mouths to the point that they had to shove pieces of food through a 5 mm opening, or were forced to subsist on a liquid diet or have repeated surgical procedures to chop away the bone. Jaw positions changed. Many developed an open bite which means their mouths were never able to close completely. Most patients experienced increased pain, while others were asymptomatic while major degeneration took place. What we heard over and over was that people had numerous surgeries and some had as many as 6 sets of implants. The record holder in our database was a woman in Pittsburgh who died at the age of 41 after her 62 nd jaw surgery. And may I remind you, the ages of these implant victims were in their teens through 50s. What we hear from these patients is that the systemic problems are as troubling as the craniofacial problems they face. 6

7 Some of the symptoms or diagnoses reported to us are fibromyalgia, neurological problems (atypical MS, dizziness, balance problems, seizures), fatigue and malaise repeated bouts of fever, night sweats, vomiting, weakness, visual problems, hearing problems and ear pain, immunological diseases, cardiovascular problems, neurological problems, sleep apnea. Many patients experienced a gradual systems breakdown which resulted in the deaths of many patients that I ve known. Unquestionably treatment failures have had devastating effects on the lives of many of the patients who have contacted us and their loved ones. In response to a survey we conducted, one patient wrote, You should have asked a question relating to personality changes. I, myself, can mark the day that everything changed for me and I became a different person. I miss the person I used to be and so does my husband of 30 years. Another said, I went into the OR one woman and came out someone different. Promising careers fade, jobs are lost, and hopes of having children are abandoned. Parents once again become caretakers of their adult children or children take care of parents. Friends are lost because of the overwhelming presence of TMJ in the patient s life and the unpredictability of knowing how you will feel from hour to hour. Dining out, contemporary society s way of interacting in a social manner is embarrassingly difficult because of the oral disability. In the 80s, groups treating TMJ advertised their seminars in dental journals and enticed practitioners by referring to this as TMJ, The Money Joint. Ironically, in other languages, TMJ is ATM. Most TMJ patients who have experienced multiple treatments are not wealthy if they once were. Because of the lack of scientific evidence to justify treatments, TMJ joins cosmetic surgery as routine exclusions to insurance policies; the patient must pay and in most cases sign contracts in order to receive diagnostic testing, splints, etc. We ve heard costs as high as $7,000. When it comes to total joint devices -- explantation of failed ones and implantation of new ones you re looking at costs in excess of $125,000 implants costing $25,000 35,000, surgery fees $25,000 and the rest in hospital costs. And you better have a certified check on the surgeon s desk one week in advance of the surgery. Spouses of TMJ patients are forced to assume household and childrearing responsibilities and often take on second jobs because of the loss of the spouse s income. Many marriages don t survive TMJ. Many couples do not share their bed. I ve heard from so many patients who sleep 7

8 in lounge chairs because if they lie down the unsupported mandible falls back and impinges on their trachea and they can t breathe. Others have nightmares and flashbacks of their multiple surgeries or are kept awake by pain. Needless to say, once pleasurable sensations like being touched, hugged, kissed, having one s face stroked, things that are an integral part of lovemaking and affection sharing, are for many excruciatingly painful. To add insult to injury those treating TMJ have very often blamed the patient for treatment failure or imply they are hypochondriacs. This usually happens after the patient has exhausted financial resources or the provider has run out of options. One patient wrote, All these years he told me my pain was psychosomatic so I continued with his treatments counseling, biofeedback, TENS, hypnosis, 13 surgeries. I cannot believe I ve been deceived all these years. The only way I learned about my condition was out of a magazine. Ten years ago a man from New Jersey called and was sobbing. He would not identify himself, just told me about his wife and then begged me to keep doing what I was doing for patients. His wife had 11 surgeries and three different implants. She was suffering greatly. He accompanied her on a visit to the oral surgeon. They sat in his office and the surgeon reared back in his chair and told the husband, There s nothing wrong with your wife that a good shrink can t cure. When they got home they argued, the husband asked his wife, He s the expert, who should I believe you or him? Upon which she went into the bedroom and shot herself. We recognize that there are clear indications for jaw surgeries and joint replacements. We also recognize that there are people who have had surgical procedures and implants that have improved their lives. However, there are so many unsolved problems, complexities and contradictions in this field compared to most others that we cannot make rational and informed decisions based on what is currently known. A treatment may work for one person and harm another. Implant failure occurs in all shades of gray. It is exactly these observations that tell us what we don t know and what we need to know to advance this field. The risk-benefit ratios of our treatments have not been determined in any scientific manner and there are no scientifically acceptable outcome studies that go beyond the patient s ability to chew and the pain index. To not have made progress in all this time indicates that we do not have the right science with the right people! Our challenge to you is to improve our odds substantially through new avenues of research with the right science and the right scientists and now! 8

9 Based on 20 years of experience and interactions with such patients and the recommendations that have resulted from the three scientific meetings of The TMJ Association, co-sponsored by multiple agencies of the National Institutes of Health, we urge the following: Generate in vitro, in vivo, transgenic and computer models of the jaw and its component parts, making use of data from human and animal studies of jaw motion and load-bearing characteristics. Data from failed and explanted jaw devices will also be valuable in constructing dynamic models robotic jaws, if you like. As far as materials are concerned you are well aware of the range of tests needed to assure against deformation, wear, and incompatibility with human tissues. You also know the potential for combining inert materials with living cells and resorbable scaffolding to construct a working joint. Today s ever-improving imaging techniques are essential aids in your research, enabling a fine tuning of the anatomy and physiology of the joint, including its blood supply, its complex network of muscles and nerves and their central control. Conducting this research demands a team approach with bioengineers working side by side with mathematicians, cell physiologists, neuroscientists, geneticists, endocrine specialists and others who can talk the language of bioinformatics and gene arrays, who study how the jaw responds to stress or injury, how endocrine factors affect jaw function, and how chronic pain may contribute to progressive joint deterioration. But let s not restrict this research technique to the joint and let s not restrict it to the dental community! Until now, TMJ research has revolved around the cultural, intellectual and scientific resources available to this community, thereby drastically limiting progress in the field. It has also reinforced the disconnect with what the patients are experiencing health-wise and what those treating us think we re experiencing. Over the years, the most frustrating cry we hear from the patients is -- This is not a dental condition, it s medical! We now know that TMJ is a complex disease with associated medical co-morbidities and that alone dictates that the healthcare needs of many patients will not be met in dentistry. It is also a joint with affiliated tissue components, like all the other joints in the body joints that enjoy the benefit of the expertise of orthopedists and rheumatologists. The pain component is consistent with many other medically treated pain conditions, for example, fibromyalgia, treated in rheumatology. Therefore, it is imperative that the TMJ research teams need the inclusion of the medical 9

10 sciences if we are ever to make progress in this disease. It is way past due that we reconnect the head to the body and study the patient within the entire biological system. As we have described the team that we need to work on the TM joint, we need to expand that team to investigate the TMJ diseases and disorders in a comprehensive manner. In this postgenomic age, the biological sciences have become overwhelmingly dominated by an enormity of qualitative and descriptive facts with too little understanding of how they quantitatively relate to each other. In other words, it is not enough to know that there are genes and proteins, hormones, and so forth, but that we know how they operate together and integrally within the individual. The concept of a systems biology research approach that is emerging within the scientific community and is being encouraged by the NIH Roadmap directive is clearly necessary to study complex diseases like TMJDs. In order to initiate this approach we must develop cross-cutting teams of scientists in computational biology, bone, cartilage, skeletal muscle, vasculature, the neurosciences, endocrinology, molecular genetics, genomics, proteomics, bioinformatics, inflammation and free radical chemistry, immunology, tissue engineering and the sub-specialties that bring their expertise to bear upon these complex diseases, like TMJ. These teams must develop novel computational and experimental approaches leading to the convergence of genetic sequence, proteome data, cell, tissue and organ data into quantitative mathematical models capable of predicting the physiology and pathophysiology of the patient. Similar teams must develop novel non-invasive diagnostic approaches and safe therapies for TMJ patients. Though bioengineering is only one component of these integrated cross-cutting teams, it is you, the engineers and computational biologists that are best trained to think about how the various elements of a complex system work together to provide the whole that is greater than the sum of its parts. I recognize that this would be a remarkable achievement in any field of biology, but TMJ patients would ask why not start with us? In fact, Dr. Tabak, Director of the National Institute of Dental and Craniofacial Research, asked the same question at the close of our last scientific meeting -- Can we create a team that is truly multi-disciplinary to take what the next step needs to be in order to solve this thing? I think we can and we can begin right here at this meeting! The topics being discussed are state-of-the-art in 10

11 their respective areas and I must say exciting to this TMJ patient advocate! Though the culmination of such a team project may be years off -- you, the attendees at this meeting have the opportunity to form the collaborations and team building that I described and endorsed by the NIH and requested by Dr. Tabak. Such team science will yield the information that will improve the quality of healthcare and life for the millions of TMJ patients. The hope of the patients is in science and I hope you will join us in changing the face of TMJ. Let me close by giving you a few specific directives from some of the patients I surveyed in anticipation of this meeting. Betsy in Minneapolis asked me to, Tell them to design a joint that will let me chew, talk, cry, swallow and smile without pain, one that will restore my mandibular function and my facial structure.one that will not make me worse than I already am or eventually kill me. Oh, and be ready to prove to me that it does all those things. That sentiment was echoed by all the patients with whom I talked. Other requests are, Please find out why we keep growing heterotopic bone. Study TMJ in connection with other connective tissue diseases. For example, are there inheritable differences in the makeup of the collagens in the TMJ disc and other regions such as the mitral valves that predispose them to dysfunction? Importantly, why are women more likely to get TMJ disorders and does being a woman predispose them to greater implant failure? Could we get away from hardware joints, please? For those of us in the cold climates the metal conducts the cold and causes me to get migraine headaches. Sometimes the imprint of the device stays on my skin for a day. Lastly, patients ask why they aren t consulted by device teams. I encourage you to talk to the patients, form focus groups and just let them talk about the experience of having implants. You ll be surprised what you will learn. In the recent past patients and patient advocates have become partners with those involved in the science that affects their lives. I encourage you to contact me if you think that those involved with this organization or I may be helpful to you in anyway. I m honored to represent the TMJ patients at this most important and impressive meeting and I thank you for the opportunity. 11