Causes of Ischemic Bone Damage

©The Maxillofacial Center for Diagnostics & Research

Other Links

NICO Clinical Page
NICO Home Page
Home Page


A Very Brief Review
The Causes
The Clotting Disorders

Typical NICO cavitation appearance on x-ray: oval, poorly-defined radiolucency (cav) with hint of peripheral sclerosis; 
hollow space extends to ends of dotted line.  "Xs" mark a residual lamina dura (laminar rain).

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


A Very Brief Review of Ischemic Osteonecrosis

Ischemic osteonecrosis means, literally, "dead bone from poor blood flow."  It may have either dead bone or bone marrow that has been slowly strangulated or nutrient-starved.  Bone with chronically poor blood flow 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.

The Causes of Ischemic Osteonecrosis of the Jaws (NICO)

Ischemic osteonecrosis is not so much a disease in its own right as it is the localized 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).  Some of these etiologic factors are much more significant than others.  Some are primary causes and others act as triggering mechanisms or "second hits" in persons otherwise susceptible to bone marrow flow problems.  

The most important underlying, and almost always undiagnosed, susceptibility comes from coagulation disorders, i.e. an hypercoagulation state or prothrombotic state.  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.  For more detail about the hypercoagulable states, click on the hypercoagulation button at the top of this page.

The jaws are especially susceptible to reduced blood flow problems.  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?), and oral or root canal (endodontic) or gum (periodontic) surgery.  To these potential causes we can add others which are rather unique to dental procedures: local anesthetics used to numb to jaw for tooth procedures 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 one of the undiagnosed hypercoagulation disorders previously mentioned.  Moreover, the poor outflow characteristic of osteonecrosis means that the vasoconstrictor can remain in the area much, much longer than the few minutes needed for profound local anesthesia.  And to add injury to insult, literally, the reperfusion of the bone after the vasoconstrictor wears off releases large numbers of tissue-damaging oxyradicals.   Normal tissues can withstand this onslaught nicely, but a nutrient-starved ischemic marrow is at risk.

Additional risk factors for ischemic disease of the maxillofacial bones include the common practice of prescribing prednisone or prednisolone to prevent swelling after oral surgical procedures.  Corticosteroid use is the most common cause of non-traumatic osteonecrosis.  Although the risk appears to be dose dependent and time-of-use dependent, there are reports of massive hip disease from a single week's use of Medrol.  And finally, recurring maxillary sinus infections with potential seeding of bacteria as far as the alveolar bone, producing osteomyelitis (bone infection), is a major risk factor.  The inflammatory mediators at work in this chronic process are capable of increasing local and systemic coagulation.  This is generally not a problem for a normal person but can be, again, disastrous for the 6% or more of us who have undiagnosed or "silent" hypercoagulation states.


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

Disease or Etiologic Factor


Alcohol abuse



Subchondral cyst
Subchondral marrow edema

Atmospheric pressure variations

Caisson's disease
Deep sea diving

Blood dyscrasias

Disseminated intravascular coagulation
Sickle cell anemia


Chemotherapy for cancer
Cancer-induced hypercoagulation
Metastatic intraosseous carcinoma
Radiation therapy for cancer

Chronic inactivity

Full body cast


Inflammatory bowel disease
Lupus erythematosus


Birth control pills
Estrogen replacement therapy
Fertility drugs
Prostate chemotherapy
Transient ischemic osteoporosis

Gaucher's disease




Hypercoagulable state, local

Acute infection/inflammation
Chronic infection/inflammation
Increased intramedullary pressures

Hypercoagulable state, systemic

Antiphospholipid antibody syndrome
Factor VLeiden gene mutation Hyperhomocystinemia
Homozygosity for MTHFR or CBS *
Protein C deficiency
Protein S deficiency

Hyperlipidemia & embolic fat

Diabetes mellitus
Dysbaric phenomena
Fracture of bone
Osteomyelitis, acute

Hypersensitivity reactions

Allograft organ rejection
Anaphylactic shock
Immune globulin therapy
Shwartzman reaction to endotoxin
Transfusion reactions





Inflammation, intraosseous

Infection, bacterial and viral
Trauma (mild or severe)

Lupus erythematosus

With corticosteroid therapy
Without corticosteroid therapy


Brain injury/surgery


Regional or generalized


Anorexia nervosa

Storage diseases

Gaucherís disease

Tobacco use

Tobacco smoking

Vascular occlusive disease





Local anesthetic use
Raynaudís phenomenon

* MTHFR: methylene tetrahydrofolate reductase ; CBS: cystathionine beta-synthetase


Table 2: Coagulation disorders found in patients with ischemic osteonecrosis of the hips, knees and jaws, compared to the proportions found in patients with deep vein thrombosis of soft tissues and with the normal population. Thrombophilia = increased tendency to develop thrombi; hypofibrinolysis = reduced ability to lyse thrombi.

Coagulation Defect Normal
Deep Vein
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) 2-7% 20-50% 65-87%

                   * usually autosomal dominant