Clinical Features of 
Maxillofacial Osteonecrosis (NICO)

Hollow mandibular space (cavitation) seen in subpontic region 
of old extraction site (bridge is removed).
Photo courtesy of Dr. Thomas Colpitts, Tulsa, Oklahoma

Patient Age & Gender

Maxillofacial osteonecrosis (NICO) has been microscopically confirmed in patients as young as 14 years of age and as old as 94, and has been reported in both genders.  However, three-fourths of patients are 35-64 years of age and three-fourths are women.  These age and gender predilections are similar for patients with pain and those without pain.

Location of Lesions

Jawbone sites most often involved, in decreasing order of frequency, are the mandibular molar/retromolar areas, the maxillary molar/tuberosity areas, and the maxillary cuspid/lateral incisor areas (Table 1). Third molar (wisdom tooth) sites account for 45% of all jawbone involvement.  The vascular inflow of the mandible is quite different from the maxilla and one would not, therefore, expect even distribution of a vascular disease , but osteonecrosis is generally a disease of infarction and thrombosis of small vessels ischemic damage is more likely to occur in the distal portions

Most maxillofacial lesions are in old extraction sites, but another common presentation is a radiographically successful endodontic procedure which continues to be painful after therapy, even after extraction.  While the great majority of facial cases occur in the alveolar bone, i.e. the bone containing the teeth, osteonecrosis can affect the walls of the sinuses, walls of the external ear canal (malignant otitis externa), and the TMJ  or jaw joint (avascular necrosis of the condyle).  

Table 1: Location of 2,301 NICO lesions as reported on biopsy request forms from 1,333 patients with facial pain. Numbers represent the proportion (%) of all cases found at a specific site, first surgery only.

                                                            * includes tuberosity and retromolar areas

Multiple Sites are Often Involved

One-third of NICO patients have more than a single quadrant involved, not necessarily at the same time, and 10% have lesions in all four quadrants.  This is not unexpected, as it has long been known that 50-80% of hip cases eventually involve the opposite femoral head.  In our experience, the more generalized the condition, the more likely the jawbone patient is to suffer from multiple risk factors, including hyperthrombotic disorders.

Clinical Signs of Disease are Few

Maxillofacial osteonecrosis produce only subtle, if any, inflammatory changes of overlying soft tissues, including transient erythema (redness) and edema (swelling), but microscopic analysis of the overlying soft tissues demonstrates mild to moderate numbers of chronic inflammatory cells beneath the epithelium.

Sinus involvement.  Recurrent sinusitis may involve the bony walls and floor of the maxillary sinus, allowing bacteria and/or inflammatory toxins into alveolar bone on a recurring basis and perpetuating osteomyelitis/osteonecrosis of multiple maxillary sites. Roberts et al have suggested injecting a radiopaque dye into the maxillary sinus, with periapical radiographs taken at 20, 40, and 60 minutes, as a means by which to identify areas of sinus wall or floor perforation not otherwise apparent. Other walls are also affected, but less frequently. Some patients have shown considerable destruction of the infraorbital bone, and the lateral nasal wall appears to be especially susceptible, perhaps because of the popular use of corticosteroid nasal sprays.

Pain

Tenderness (Pain on Touching). Most maxillary lesions, especially those of the tuberosities (behind the upper wisdom teeth), are tender to palpation or can be aggravated by pressure, perhaps even triggering a "jump sign" similar to that elicited when palpating myofascial trigger points (see Travell & Simons). Mandibular lesions are more difficult to identify with digital pressure, presumably because of the greater density of the cortical bone.  A lack of local tenderness in the area of pain or of referring pain makes the diagnosis more difficult but does not exclude underlying marrow disease.  McMahon et al (1998) have shown that chronic inflammatory cells are found in small numbers beneath the mucosa in these areas of tenderness, presumably because of neurogenic inflammatory reactions.

In 1995 Friedman found focal areas of alveolar bone tenderness within the quadrant of pain in 15 of 18 patients with atypical facial neuralgia/pain; 17 of the 18 patients demonstrated a focus of increased mucosal temperature in the quadrant of pain.

Pain (Without Touching). When pain is associated with ischemic osteonecrosis of the jaws it is usually diagnosed as atypical facial neuralgia/pain (67% of all pain-associated cases) or trigeminal neuralgia (10%) until a jawbone lesion is discovered.⁶¹ 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 (range: 1 month to 32 years) before a jawbone biopsy confirms the presence of ischemic osteonecrosis or low-grade osteomyelitis.⁶¹ 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.

The pain in this disease can be produced by a variety of factors, such as ischemia of the nerves, fluid or gasseous pressures on the nerves, distended blood vessels, inflammatory mediators, damage to the nerves from chronic exposure to the toxins of dead or inflamed tissues.  It should not be surprising, then, that a variety of types of pain occur.  Most patients feel a deep ache or sharp pain deep in the bone.  This is often difficult to localize and may, in fact, move about from day to day or week to week (remember, the disease is a fluid/pressure phenomenon with small infarctions occurring over time).   Pain episodes may be separated by days or weeks without pain. Another common pain type is a very sharp, lancinating pain shooting up to the eye or along the edge of the nose or back to the ear, perhaps with temporary secondary pain in those sites.  This pain may or may not be triggered by touching a certain part of the alveolar bone or overlying facial skin.  Some patients describe their deep pain as "annoying" or "uncomfortable" rather than true pain, but these generally will go on to more severe pain over time.

Two abiding features of NICO pain are: the pain responds poorly to pain killing medications (except morphine) while likely to respond well, temporarily, to "anti-seizure" medicines, such as Tegretol and Neurontin; the pain in approximately 15% of cases will disappear for several days, weeks or months after injection of the primary site of pain with local anesthetics.  The reason for the former phenomenon is unknown, but may be related to myelin (nerve sheath) damage from the toxins of the diseased marrow.  The latter phenomenon may have to do with the fact that intraosseous blood flow is so slowed in some individuals that the anesthetic remains in place for long periods of time.  A third feature of NICO is that a local dental anesthetic injected into the periosteal tissues above the site of diseased marrow almost always reduces or completely eliminates the pain.

Other Symptoms

It is quite common for a patient to complain of an annoying pressure sensation in the area of involvement.  The pressure may, in fact, be a real phenomenon, as osteonecrosis is associated with internal bone pressures much higher than normal.  While the jaw cases have not been analyzed in this regard, surgeons have experienced lesions with enough pressure to produce an audible release of air when the cortex was surgically removed.  Occasionally, necrotic marrow debris will come "flying" out of the cavitation.  An additional common sensation in maxillofacial osteonecrosis patients is a strong sensation of burning deep in the bone.  This may be indicative of damage to the nerves themselves, but that has not yet been established.

One of the frightening features of ischemic osteonecrosis is the very large number of systemic and local diseases and factors capable of damaging the bone marrow.  Jones has listed them for years, with the list expanding dramatically in recent years (Table 2). 

More information relative to the causes of NICO.

Cavitations Defined & Explained



Completely hollow mandible ("dry rot") with 
alveolar nerve almost floating freely in cavitation.

Certainly one of the most unique and fascinating features of ischemic osteonecrosis is the presence of hollow spaces or "cavitations" within the marrow spaces.  By definition these must be larger than 5 mm. in diameter to warrant the use of the term cavitation, but in reality many older persons have smaller hollow spaces scattered throughout their bone marrow, at least as determined by Graff-Radford's cadaver study of the jawbones.  An expression of the uniqueness of these lesions can be found in the fact that the the first (1930) and only application of the term to bone pathology was for ischemic osteonecrosis and its variants.  

These spaces essentially represent "dry rot" of the bone and fatty marrow, a process which can only be explained by slow and chronic strangulation of the bone's blood supply, i.e. ischemia. In persons with a generalized marrow ischemia, such as those taking estrogen or corticosteroids, alcoholics or those with autoimmune diseases such as lupus erythematosus, multiple cavitations are common. Any bone can have them, but those most susceptible are the hip, the jaws and the knees. They may be associated with increased medullary pressures and are often associated with local or referred pain.

Cavitation can occur in only one of two conditions, according to osteonecrosis authorities consulted by this Center: ischemic osteonecrosis and unicameral bone cyst (called traumatic bone cyst in the jaws). The necessary ischemia is apparently a part of several significant bone diseases, such as osteoporosis (subchondral bone cysts) and florid osseous dysplasia (with traumatic bone cysts) of the jaws.

Most cavitations in the jaws are found in the third molar regions, and in the maxilla this phenomenon is referred to as a "hollow tuberosity." The walls are usually irregular and are often discolored brown and black ("blowtorched" appearance), but a sizeable proportion of lesions have very smooth, very hard (marble-like) walls. The more smooth the walls, the less likely is the cavitation to have a pool of blood at its base and the less likely it is to bleed during surgery (some examples have presented with almost no hemorrhage until the damaged/altered bony wall is removed and the surgeon enters the surrounding fatty marrow).

[Photo album of jaw cavitations, use NICO home page link to return to this page]

While many health professionals refer to the disease of osteonecrosis, or the resulting pain, as cavitations, these hollow spaces are not, in fact, the real disease. They merely represent one manifestation or sign of ischemic osteonecrosis, a disease produced by chronically poor blood flow through bone marrow. It is true that curetting the walls of a cavitation seems to eliminate or greatly reduce the pain of osteonecrosis, but this probably results from a combination of: the elimination of local toxins from necrosis and inflammation (and maybe from bacteria); the release of fluid or gaseous pressures in the marrow; the stimulation of fresh hemorrhage into this dried out area. Treating the cavitation is, however, not treating the disease itself, it is only treating one sign and perhaps a few associated symptoms, such as pain, pressure and a burning sensation.

Although ischemic marrow damage can be produced by a large number of systemic diseases, they result in a surprisingly small number of bone diseases.  Many names have been given to ischemic osteonecrosis and bone marrow edema over the years (click for listing) but excluding these, the following table lists those few bone diseases capable of creating true, "air-filled" intramedullary cavitations or hollow spaces.

Palpation

One of the most simple, most valuable and most often overlooked diagnostic tools for the localization of chronically diseased marrow is palpation of the alveolar bone by finger or blunt instrument pressure.  Nerve endings from hypersensitized alveolar nerves chronically attacked by marrow ischemic and inflammatory phenomena extend partially into the overlying periosteum and mucosa, imparting a mild to moderate (sometimes severe) tenderness to the area.  This is seldom accompanied by mucosal redness or swelling, although biopsy will typically show small numbers of scattered subepithelial and perivascular lymphocytes in the area, as a result of neuropathic inflammation.  The tender spot might not be in the region of the patient's pain, but diagnostic anesthesia into the region usually will confirm the site as the source of the pain.

Abnormal Responses to Local Anesthesia

Pain response to local anesthetics is used as a diagnostic tool in maxillofacial osteonecrosis (anesthetic confirmation, diagnostic local anesthesia).  Box appears to be the first to report the use of anesthetic confirmation, and recent authors have reaffirmed its usefulness, but it was Ratner & colleagues and McMahon and colleagues who developed a specific protocol of diagnostic local anesthetic injections for localizing the lesion(s) and determining the association between the diseased bone and the pain dilemma. In sorting out pain-producing mandibular pathology, this anesthesia/hyperesthesia test depends on localizing small zones of unanesthetized gingiva in an area which would normally be expected to be anesthetized after inferior alveolar and long buccal nerve blocks. These tissues are then directly infiltrated in order to obtain complete analgesia and checked for "full terminus" anesthesia (complete, to the lip).

Pain-producing maxillary pathology, whether dental or osseous in origin, can be assessed by beginning anteriorly and selectively infiltrating buccally and palatally, proceeding posteriorly, until the pain has been extinguished. Because of the many snares of referred trigeminal pain phenomena, the reader is encouraged to review Ratner et al and McMahon et al for further details. The reader is especially reminded to use only anesthetic solutions without vasoconstrictors, in order to avoid further compromise of a marginally inadequate medullary blood flow.

Electro-Acupuncture Testing

A certain number of dentists submitting biopsied tissue samples for maxillofacial osteonecrosis evaluation seem able to localize intramedullary disease through the identification of electrical disturbances of the mucosal surface. This is done through an electronic sensing device called a Computron. These practitioners may combine oral findings with diagnostic acupuncture techniques, a practice initiated by Voll and often called EAV, or electro-acupuncture according to Voll. Much research needs yet to be performed to more substantially validate this technique, but an informal review of tissue submitted for microscopic interpretation has shown that ischemic and inflammatory marrow disease is identified positively at the same level as that of practitioners using more conventional diagnostic techniques: somewhat more than 90% of samples submitted with a NICO or maxillofacial osteonecrosis clinical diagnosis prove to be so on microscopic evaluation.