Maxillofacial Osteonecrosis (NICO*)
A Review for Patients
Frequently asked Questions
 

It's diseased marrow from poor blood flow.
Ischemic osteonecrosis (literally, "dead bone from poor blood flow") is a bone marrow disease with either dead bone or bone marrow that has been slowly or abruptly strangulated or nutrient-starved. It is not so much a disease in its own right as it is the localized result, in any bone, of anything which significantly reduces the blood flow through the bone marrow.  Once called coronary disease of the hip because of the associated marrow ischemia (reduced blood flow) and infarction (complete blockage of a vessel) in cases involving the femoral head, the list of diseases and biological phenomena capable of producing this damage has grown to an impressive size during recent years (click on "The causes" on left).

It is not an infection.
Ischemic osteonecrosis, even in its mild or minor forms, creates a marrow environment that allows bacteria to grow, and since many persons have low-grade infections of the teeth and gums, this probably is one of the major mechanisms by which the marrow blood flow problem becomes worse (any local infection/inflammation will cause increased pressures and clotting)...no other bones have this mechanism as a major risk factor for osteonecrosis. Are the bacteria there? Usually. Is it a single, unique bacteria? No, a wide variety of bacteria have been cultured from NICO lesions. Typically, they are the same bacteria as those found in diseased gums or teeth. Are the bacteria present in large numbers? Almost never, according to special staining of biopsied tissues. Is NICO an infection? Usually not, but many cases have a secondary, very low-level of bacterial infection. Fungus infections do not seem to be a problem, but viral infections have not been studied. Some viruses, such as the smallpox virus (no longer existent) produce osteonecrosis in at least 5% of infected persons, usually in the leg bones.

It presents in different ways.
Regardless of the underlying cause, the bone develops either a fibrous marrow (fibers can live in nutrient starved areas), a greasy, dead fatty marrow ("wet rot"), a very dry, sometimes leathery marrow ("dry rot"), or a completely hollow marrow space ("cavitation"). Pain may or may not be part of the disease. Special tests, such as the tech99 bone scan (on left) may be needed to find the areas of diseased marrow, they often do not show up on x-rays.
    

NICO: Neuralgia-Inducing Cavitational Osteonecrosis (pronounced "neeko")
When jaw osteonecrosis, i.e. bone damaged by poor blood flow,  is painful it is given the name of NICO (neuralgia-inducing cavitational osteonecrosis). For those patients without pain, the more generic term, maxillofacial osteonecrosis can be used, although some prefer the term silent NICO, in keeping with the orthopedic surgeons' use of silent hip for painless osteonecrosis of the hip. The name NICO was first used in 1989 in a research paper presented to the International Association for Dental Research. It incorporates the two most unique features of osteonecrosis, i.e. the often neuralgia-like nature of the associated pain and the hollow spaces created within the bone marrow (as in photo at left). Older names for this disease include: Robert's bone cavity, Ratner bone cyst, chronic osteitis, interference field, and trigger point bone cavity. The first report of such a lesion in the jaws dates back to the 1860s, when it was thought to be purely an infection and was often associated with severe toxicity.
   

Hips, knees and jaws are most often affected.
This disease can affect any bone in the body, but those most often affected are the hips, knees, jaws (or facial bones), and lower spine. Which bone gets involved may depend on the sex and age of the patient. Hip disease, for example, is seen in adolescent and teenage boys (Perthes disease) and in pregnant women (transient ischemic osteoporosis, regional ischemic osteoporosis) and in middle-aged men and women (avascular necrosis, bone marrow edema, ischemic osteonecrosis).  In the jaws, women aged 30-55 account for more than 80% of all cases, but they have been affected in teenagers and in persons more than 90 years of age.  Overall, this disease now is responsible for almost a third of all hip replacement surgeries performed each year, while 20 years ago it was an extremely rare reason for hip replacement (cases were misdiagnosed as arthritis).

Wisdom teeth sites are half the cases.
The wisdom tooth sites, top or bottom, are the most often involved sites (almost half of all cases), perhaps because these have the blood vessels furthest "from the heart," i.e. the ends of the longest blood vessels to the tooth-bearing regions and the place where the pressures are less and the flow is somewhat irregular -- both conditions favor the formation of clots.  Virtually any part of the jaw, however, can be involved, usually the tooth bearing bones (click on x-ray at left) but sometimes the jaw joint (temporomandibular joint) or the flat portion of bone in the back of the lower jaw,  just in front of the ears (ramus of the mandible). Sinus walls, the base of the skull, and the ear canal (external otitis maligna) may also be affected.
   

It may be very common.
Maxillofacial osteonecrosis is probably not a rare disease. In a preliminary population study of NICO cases in West Virginia, the point prevalence rate for biopsy-proven cases, i.e. the number of new and old cases in the population at a specific point in time, was one of every 2,200-5,000 adults. For middle-aged females the rate was one in every1,009-2,500. This makes NICO the second most common form of osteonecrotic diseases, affecting more than 68,000 U.S. adults annually. If the majority of affected patients have no pain, which can be inferred from the work of Dr. Box (University of Toronto), then the prevalence of maxillofacial osteonecrosis must be considerably higher than the NICO rates.
    

Middle-aged women are affected far more than others.
Maxillofacial osteonecrosis and NICO have been microscopically confirmed in patients as young as 9 years of age and as old as 94. However, more than 80% of patients are 35-55 years of age. It has been reported in both genders, but more than 80% of cases are diagnosed in women. Another disease, traumatic bone cyst, is probably a variant of osteonecrosis; it occurs primarily in the teens and twenties.
     

causes
What 
causes it?

It has multiple causes.
There are numerous of local and systemic problems capable of producing this bone disease (Table 1), but more than 4/5 of patients with osteonecrosis have a tendency, usually inherited, toward excessive production of blood clots in their blood vessels (Table 2). These are not normally picked up with routine blood studies. Bone is particularly susceptible to this problem and develops greatly dilated blood vessels (from backup pressure), increased, often painful, internal pressures, stagnation of blood, even infarctions (completely blocked vessels with death of surrounding tissues). This hypercoagulation problem might be suggested by a family history of stroke and heart attacks at an early age (less than 55 years), hip replacement or "arthritis" (especially at an early age), and deep vein thrombosis. Chronic fatigue syndrome and fibromyalgia are also associated with excess coagulation and are frequently found in patients with osteonecrosis, but the significance of this association is not yet known. The jaws have a special problem with this disease because, once damaged, the diseased bone is poorly able to withstand low-grade infections from tooth and gum bacteria.  Also, when a dentist works on a tooth he or she uses strong chemicals (vasoconstrictors, e.g., epinephrine) designed to make local blood vessels smaller and thus keep the local anesthetic in place longer.  For someone who already has a problem with poor blood flow through the jaws, this may be disastrous.
    

NICO occurs in marrow around the teeth.
Most NICO sites are old extraction sites, but many are found in the marrow around a root canal treated tooth. Typical dental infection produces granulation tissue at the ends of the roots where the endodontist does his or her surgery (apicoectomy, in region of white circles on the photo to the left).  This granulation tissue is almost always walled off from the marrow by a thin or thick bony wall. A biopsy taken from the apex, i.e. the end of the root, will not show the diseased marrow, only the dental infection.

NICO and root canal treated teeth.
The reason so many root canal treated teeth are near NICO sites is open to debate.  Some dentists believe that the treatment itself is the cause, because endodontically treated teeth always leave a certain number of bacteria in the root canal or because the body reacts to the foreign materials used to fill the treated root canal.  Moreover, studies have shown that a large proportion (more than 40%) of endodontically treated teeth are not done in a technically acceptable manner.  These are facts not disputed by endodontists. We assume that a well-performed root canal procedure cleans out enough bacteria from the root canal and provides a good enough seal at the end of the root that the body's own immune defenses can keep in check the remaining bacteria, as it does with bacteria in other parts of the body. The materials used in root canal treatment have been declared biocompatible, but this is such a difficult area of research that it is almost impossible to say that anything is completely biocompatible if left in the body over long periods of time. The usual root canal filling, gutta percha, is a rubber product which can cause an excessive immune response in some individuals.

Most NICO lesions are not associated with root canal teeth.
Blaming root canal treated teeth does not explain why the majority of NICO cases occur in the wisdom tooth areas, as these teeth are seldom treated endodontically.  But the infection and the minor surgical trauma of the root canal treatment most certainly create a mild inflammation (the body's response to infection and trauma) in the bone and marrow near the diseased tooth.  Inflammation releases several chemicals capable of increasing local blood clotting.  It is designed to do this and this phenomenon is beneficial under normal circumstances, but for a person who already has a compromised marrow blood flow, and especially one who tends to clot excessively because of an inherited clotting disorder, the minor increase in local clotting can be disastrous, leading to painful infarction and marrow death.  This phenomenon is made worse, of course, by the use of vasoconstrictors (drugs used to make blood vessels smaller) in the numbing agents or local anesthetics used during root canal treatment.  Many NICO patients first began experiencing their intense pain shortly after root canal treatment, and it continues or is made worst by extraction of the offending tooth.  But many also begin their pain saga with routine dental treatment, where nothing is done in or near the bone and the only logical explanation for reduced blood flow/infarction is the anesthetic.
    

It's an old, old disease.
Ischemic osteonecrosis is as old as the dinosaurs but only recently has it gained enough recognition to be commonly diagnosed. In humans, osteonecrosis was once a common disease in the practice of dentistry and medicine. This was due, in part, because of the popular use of mercury, arsenic and bismuth in medicinal remedies, and also because so many people had to work around the fumes of phosphorus (safety matches), lead and other heavy metals.  These chemicals all interfere with blood flow to and through the bones and settle in highest concentrations in regions of chronic infection, e.g. the gums.  Known variously as chemical osteomyelitis, bone caries (today tooth decay is called caries, i.e. destruction without pus), phossy jaw and argyria, these jawbone cases most likely represented a combination of osteonecrosis from these environmental toxins and osteomyelitis (infection of bone marrow) originating from abscessed teeth (periapical abscess) and gum disease (periodontitis).
     

It's not always painful. 
Pain from osteonecrosis is often severe, but at least a third of patients do not experience pain, whether the disease is in the long bones or the facial bones. It is extremely important to understand that osteonecrosis can produce major destruction or damage to bone marrow with minimal or no pain. In the hip, for example, it is not unusual for a patient's first sign of disease to be the collapse of the joint. In the jaws, many cases have presented with large, completely hollowed-out spaces in the marrow, with no history of pain. 

Jaw pain is like hip pain.
The pain in NICO is similar to the pain in osteonecrosis of the hip or knees or spine, but some NICO patients have extreme or unusual pain, sometimes mimicking trigeminal neuralgia, the "granddaddy" of facial pains, which presents with lightning burst of pain radiating from the mouth or face to the ear, scalp, throat or neck.  This may be related to the fact that the jaws are the only bones in humans which contain large sensory (pain sensing) nerves, all of which are branches of one of the body's most complicated and extensive nerves, the trigeminal nerve. In this light, it may be significant that facial or trigeminal neuralgias (pain from the nerves themselves) represent the largest proportion, by far, of all neuralgias in humans, representing perhaps more than 85% of all neuralgias. Could it be that branches of the trigeminal nerve are being stimulated or damaged by toxins, inflammatory chemicals, poor oxygenation and nutrition from stagnated and clotting blood, or increased marrow pressures (which can be 4-5 times higher than normal, a very painful phenomenon in and of itself) from diseased marrow as they traverse the jaws?

There are several types of associated pains.
 The pain of NICO is usually diagnosed as atypical facial neuralgia/pain (67%) or trigeminal neuralgia (10%) until a jawbone lesion is discovered.  An additional 23% are diagnosed with various headaches, sinusitis or phantom toothache/pain. The typical NICO patient has had his or her pain for approximately 6 years before a jawbone biopsy confirms the presence of ischemic osteonecrosis or low-grade osteomyelitis, some were in pain for up to 32 years before a proper diagnosis was made. The pain, and presumably the ischemic process, appears to be very slowly progressive over time, with increasing pain, increasing frequency of pain and increasing areas of involvement. The pain is often intermittent and may vary in extent, location and character over time. It is often difficult for the patient to describe and localize, and it is unusually resistant to the usual pain killers prescribed by doctors or sold over the counter.  Of the over-the-counter medications, Aleve (naproxen) may be of special help in some cases because it has the ability to open up blood vessels in bone marrow, improving the flow of blood.
     

Jawbones are especially susceptible.
The jaws and sinus walls are especially involved because so many of the causes of osteonecrosis are found in that region of the body.  Trauma and infection, for example, are primary triggering events for osteonecrosis and no other bones even come close to the level of trauma and infection experienced by the jaws, e.g. tooth and gum infections, tooth extractions, trauma (a fist to the face, perhaps?), sinus infections, and oral or root canal (endodontic) or gum (periodontic) surgery.  To these potential causes we can add two more that are rather unique to dental procedures.  Local anesthetics used to numb the jaw for dental work or oral surgery contain powerful chemicals (vasoconstrictors, e.g. epinephrine) designed to drastically reduce the blood flow in the area, thereby keeping the anesthetic in place longer and allowing more time to work.  This is good for the procedure itself but can be disastrous for someone with an underlying, and usually undiagnosed, coagulation disorder.  As it turns out, more than 6% of the population has such clotting disorders and 4/5 of osteonecrosis patients have them, regardless of which bone is involved. These disorders are of the type that are not picked up with routine blood studies. Click on "The causes" on the left for more detail.
      

It often involved multiple sites.
Ischemic osteonecrosis is well known to affect multiple bones and multiple sites of the same bone. When one hip is affected, for example, there is a 50-80% chance of the disease eventually occurring in the other hip. One-third of NICO patients have more than one quadrant of the jaws involved, not necessarily at the same time, and 10% have lesions in all four quadrants.  In our experience, the more jaw sites involved, the more likely the patient is to suffer from multiple systemic risk factors, including hypercoagulation disorders.
     

Overview/problems of treatment.
The bone has trouble healing under chronic conditions of ischemia or poor nutrition. In long bones it has been shown that about 1/3 of cases do indeed heal themselves, without the aid of a doctor. For the majority of cases, however, experience has shown that surgically removing the damaged marrow will "cure" the disease (and the pain). In the jaws, diseased marrow is usually removed by carefully scraping with curettes (firm scalpels). This eliminates the problem in almost 3/4 of patients, but repeat surgeries, usually smaller procedures than the first, may be required. Moreover, almost a third of jawbone patients will need surgery in one or more other parts of the jaws because the disease so frequently has "skip" lesions, i.e. multiple sites in the same or similar bones, with normal marrow between. In the hip, at least half of all patients will get the disease in the opposite hip over time; this phenomenon occurs in the jaws as well. Recently, it has been found that some osteonecrosis patients respond to anticoagulation therapies. At the present time there is no completely effective treatment for osteonecrosis. The following therapies have been tried for maxillofacial osteonecrosis (NICO) with variable success.

Curettage of the bone lesion is the standard treatment.
The abnormal intrabony tissues usually must be surgically removed via decortication and curettage, i.e. removing the outer hard layer of bone and scraping out fragments of diseased bone marrow. Once the bony walls of the defect feel hard and look normal again, the bony defect frequently heals and the intense facial pain subsides dramatically or disappears completely. This results in a 5-year "cure" (pain free) rate of at least 70% (Table 4), although many patients must have additional curettage procedures in the same site before the treatment "takes" and the bone is able to properly heal itself. A third of NICO patients thus treated, however, experience minimal or no pain relief, and 3% experience increased pain.

Antibiotics may work temporarily, usually don't.
Antibiotics may temporarily diminish the associated pain of NICO in cases with superimposed low-grade infection, but they are unlikely to effect cure. This is, in part, because  bacteria are usually present only in small numbers, and in part because the poor blood flow and scar tissue formation doesn't allow the antibiotic to get to the bone marrow in high enough concentrations to do much good.

Hyperbaric therapy may work, usually doesn't.
Combining surgery with antibiotic therapy, or surgery with hyperbaric chamber therapy, seems to have a slight positive effect on the outcome. Some NICO patients have experienced dramatic pain reduction; a few have experienced increase in pain.

Anticoagulants work in half the patients, but have side effects.
When systemic hypercoagulable states co-exist with other risk factors, the use of various anticlotting therapies (stanazolol, Coumadin, low molecular weight heparin, etc.) may prove to be of great benefit, as indicated by a recent study showing significant pain reduction with medication (no additional surgery) in at least 50% of patients who failed to improve with prior NICO surgery. Patients with homocystinemia associated with homozygosity for MTHFR can be treated with folic acid and pyridoxine. As a cost-effective follow-up measure, INR ratios can be determined and should remain in the 2.5-3.0 range for optimal coagulation function.
     

Many cases recur (never heal?), sometimes many times.
As we would expect in a disease which is often merely a sign of underlying systemic disorders, NICO has a strong tendency to recur and/or to develop in additional jawbone sites (1/3 of cases), often requiring multiple repetitions of the same surgical procedure. This is also true of osteonecrosis of the hips and knees. In jaw patients, thirty percent of affected patients who have subsequent post-surgical reduction of pain experience local recurrence of facial pain, although it is often of a different type or location than the original pain. Nevertheless, despite a high rate of recurrence and of new primary lesions necessitating multiple surgeries, the long-term (average = 4.6 years) abatement of neuralgia pain is total or almost total in 73% and moderate in an additional 16% of cases. Only 11% of patients consider the surgery to be without merit for the treatment of their maxillofacial pain. Appropriate pain management strategies with narcotic medications, psychological counseling and even temporary disability status with periodic family counseling should be considered in severe cases (70% of whom are disabled by pain). With future research, even this group of individuals may be helped by new therapeutic techniques, but until then we must be content with the suggestion by G. V. Black, the Father of Modern Dentistry, to remove "every particle of softened bone" and expect that "generally, the case makes a good recovery."