Maxillofacial Osteonecrosis (NICO), A Review for Patients

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Mandible of patient with chronic facial pain. Brown mush represents areas
 of necrotic (dead) marrow, with scattered cystic spaces or "cavitations." 

The Maxillofacial Center, 165 Scott Avenue, Suite 100, Morgantown, WV 26508 USA
Phone: 304-292-4429   Fax: 304-291-5149    Email: MFC@aol.com


A Note to Patients with Jawbone Osteonecrosis (NICO, "neeko")

You have microscopic evidence of ischemic osteonecrosis (literally, "dead bone from poor blood flow"), a bone marrow disease with either dead bone or bone marrow that has been slowly strangulated or nutrient-starved. There are a number of local and systemic problems capable of producing this bone disease (Table 1), but more than 4 of every 5 patients with osteonecrosis have a problem, usually inherited, of 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, increased, often painful, internal pressures, stagnation of blood, even infarctions (completely blocked vessels). 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. 

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"). Any bone can be affected, but the hips, knees and jaws are most often involved. Pain is often severe but about 1/3 of patients do not experience pain. The body has trouble healing itself from this disease, but about 1/3 of cases do indeed heal themselves. For the others, experience has shown that surgically removing the damaged marrow, usually by scraping with curettes, will eliminate the problem (and the pain) in almost 3/4 of patients with jaw involvement. Repeat surgeries, usually smaller procedures than the first, may be required, and 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.

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A Somewhat Less than Brief Review of NICO

It is "dead or starved bone" from poor blood flow.  Ischemic osteonecrosis (literally, "dead bone from poor blood flow") is as old as the dinosaurs but only recently has it gained enough recognition to be commonly diagnosed.  It is not so much a disease in its own right as it is the localized (in any bone) result 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, Table 1 provides an abbreviated summary.

This disease can affect any bone in the body but the hips, knees and jaws (or facial bones) are most often attacked. It can also attack at any age, with hip lesions being 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 a rare reason for hip replacement (we were calling them simply arthritis)

An old, old disease.  Osteonecrosis was once a common disease in the practice of dentistry because of the mercury, arsenic and bismuth in popular medicines, and also because some many people had to work around the fumes of phosphorus (safety matches), lead and other heavy metals.  These chemicals all interfere with the 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, jawbone cases, then, 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).

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Why are jaws susceptible?  Even today 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 are the primary triggering events for osteonecrosis and no other bones 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 wonderful 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 (surprise! surprise!) 4 out of 5 osteonecrosis patients have them, regardless of which bone is involved (Table 2). and these disorders are of the type that are not picked up with routine blood studies (Table 3).  

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Disease names, with and without pain Many names have been used in the past for osteonecrosis of jaw bones.  The most popular term in use today is NICO (neuralgia-inducing cavitational osteonecrosis), but the term is usually reserved for those cases associated with chronic facial or jaw pain.  For those without pain, the more generic term, maxillofacial osteonecrosis (MFO) 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.  Whether or not there is pain, however, 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.

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?

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.

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Who Is Affected and Where? Maxillofacial osteonecrosis (MFO) has been microscopically confirmed in patients as young as 12 years of age and as old as 94, and has been reported in both genders. Typically, however, more than 80% of patients are 35-55 years of age and an equal proportion are women.  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 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).  

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 generalized the condition, the more likely the jawbone patient is to suffer from multiple risk factors, including hypercoagulation disorders.

Most MFO sites are old extraction sites, but many are found in the marrow around a root canal treated tooth, not at the ends of the roots where the endodontist does his or her surgery (apicoectomy).  In other words, a biopsy taken from the usual site, i.e. the ends of the roots, will not show the diseased marrow, only the dental infection.  

The reason so many root canal treated teeth are near MFO 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 of endodontically treated teeth are not done in a technically acceptable manner.  These are, in fact, features not disputed by the endodontists themselves, although they naturally assume that a well-performed root canal procedure cleans out enough bacterial from the root canal and provides a good enough seal at the end of the root that the body's own immune system can take care of the residual bacteria which might make it out of the canal.  Likewise, the materials used have usually been declared biocompatible, although 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.

Blaming root canal treated teeth does not explain why the majority of MFO 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 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.

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Is There an Effective Treatment?

At the present time there is no completely effective treatment for osteonecrosis. The following therapies have been tried for MFO with variable success.

Antibiotics. Antibiotics may temporarily diminish the associated pain of NICO in cases with superimposed low-grade infection, but they are unlikely to effect cure.

Curettage of bone lesion. 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 (Table 4). A third of NICO patients thus treated, however, experience minimal or no pain relief, and 3% experience increased pain.

Hyperbaric therapy. Combining surgery with antibiotic therapy, or surgery with hyperbaric chamber therapy, seems to have a slight positive effect on the outcome.

Anticoagulants. When systemic hypercoagulable states co-exist with other risk factors, the use of various anticlotting therapies (stanozolol, 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.

Recurrence of lesions. 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. Thirty percent of affected patients who have subsequent post-surgical reduction of pain experience local recurrence of jaw or facial pain, 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 (Table 6). 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 to remove "every particle of softened bone" and expect that "generally, the case makes a good recovery."

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How Common Is Maxillofacial Osteonecrosis?

Maxillofacial osteonecrosis does not appear to be 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 Box, then the prevalence of maxillofacial osteonecrosis must be considerably higher than the NICO rates.

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Table 1: Diseases, events, etc. associated with osteonecrosis of any bone.

Diseases/Phenomena Associated with Ischemic Osteonecrosis

Coagulation Disorders (Hypercoagulation)

Alcohol Abuse (Cirrhosis/Pancreatitis)

Estrogen or Cortisone/Prednisone Therapy

Cancer chemotherapy

Arteriosclerosis

Sickle cell anemia

Tobacco Use

Deep sea diving

Lupus erythematosus

Starvation (e.g. anorexia nervosa)

Arthritis & osteoporosis

Shwartzman reaction (serum sickness)

Osteomyelitis (infection in bone marrow)

Chronic inactivity (e.g. leg in cast)

Hypertension (high blood pressure)

Congestive heart failure (weak heart beat)

Local anesthesia use

Raynaud's phenomenon

 

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Table 2: Coagulation disorders found in patients with ischemic osteonecrosis of the hips, knees and jaws (NICO), compared to the proportions found in patients with deep vein thrombosis, a major clotting disorder, and with the normal population. Thrombophilia = increased tendency to develop clots inside vessels; hypofibrinolysis = reduced ability to breakdown the small clots always being formed and dissolved in blood vessels.

Coagulation Defect

Normal
Population
Deep Vein
Thrombosis

Osteonecrosis
Thrombophilia, hereditary types* 2-5% 5-9% 50-70%
Thrombophilia, acquired types 3-7% 20-50% 33%
Hypofibrinolysis, hereditary types * <1% 5-15% 18-22%
Hypofibrinolysis, acquired types <1% 20-25% 50%
Total (includes multiple coagulopathies) 4-7% 20-50% 65-87%

* usually autosomal dominant, i.e. it is not related to the gender of the child and each new baby has a 50% chance of inheriting the problem.

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Table 3: Coagulation disorders found in NICO patients who failed to improve with decortication and surgical debridement.

Coagulation Disorder

% In NICO

High levels of plasminogen activator inhibitor (the major inhibitor of fibrinolysis) 18%
Low levels of stimulated tissue plasminogen activator (the major stimulator of fibrinolysis) 22%
Low levels of Protein C or Protein S (thrombophilia) 8%
Resistance to activated Protein C (thrombophilia) 18%
High levels of lipoprotein A (a strongly atherogenic and hypofibrinolysis lipoprotein) 36%
Elevated levels of anticardiolipin antibodies (associated with thrombophilia and damaged endothelial cells) 33%
Factor V Leiden gene, heterozygotic by PCR DNA analysis (causes resistance to protein C) 23%
Methylene tetrahydrofolate reductase (MTHFR) mutation, heterozygotic or homozygotic by PCR DNA analysis (causes homocysteinemia and thrombophilia) 65%
Total ( includes patients with multiple coagulopathies): 78%

           

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Table 4. Long-term results of surgical curettage of NICO lesions of the jaws of 103 patients with facial neuralgias (atypical facial neuralgia or trigeminal neuralgia). Seventy-eight percent of individual lesions required only one surgery; 32% of patients had NICO in multiple quadrants. Patients were surveyed 1-18 years after last NICO surgery (average: 4.6 years). Only patients with follow-up ratings of 3 or 4 were considered cured. (Modified from ref. #61)

Follow-up Rating Reduction % Pain Present Status of Pain % of Total Cases
0 0-10 No improvement 8.8 *
1 11-33 Minimal improvement 2.9
2 34-75 Moderate improvement 15.5
3 76-99 Considerable improvement ** 13.6
4 100 No pain 59.2
Total: 100.0 %

 * 2.9% experienced increased pain after surgery (long-term)
** patients consider themselves cured, are taking no prescription medications for pain, and describe their pain condition as "almost gone," "only an occasional problem," or "very livable."

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