which premature cell death can occur depends on the cell type and the degree and duration of the anoxia. haematopoietic cells, in bone marrow, are sensitive to anoxia and are the first to die after reduction or removal of the blood supply. in anoxic conditions they usually die within 12 hours. experimental evidence suggests that bone cells composed of osteocytes, osteoclasts, and osteoblasts die within 12–48 hours, and marrow fat cells die within 120 hours. the death of bone does not alter its radiographic opacity nor its mineral density. necrotic bone does not undergo resorption; therefore, it appears relatively more opaque. attempts at repair of ischaemic-damaged bone will usual occur in 2 phases. first, when dead bone abuts live marrow, capillaries and undifferentiated mesenchymal cells grow into the dead marrow spaces, while macrophages degrade dead cellular and fat debris. second, mesenchymal cells differentiate into osteoblasts or fibroblasts. under favorable conditions, layers of new bone form on the surface of dead spongy trabeculae. if sufficiently thickened, these layers may decrease the radiodensity of the bone; therefore, the first radiographic evidence of previous osteonecrosis may be patchy sclerosis resulting from repair. under unfavorable conditions repeated attempts at repair in ischaemic conditions can be seen histologically and are characterized by extensive delamination or microcracking along cement lines as well as the formation of excessive cement lines. ultimate failure of repair mechanisms due to persistent and repeated ischaemic events is manifested as trabecular fractures that occur in the dead bone under functional load. later followed by cracks and fissures leading to structural collapse of the area involved (osteocavitation). diagnosis classification gradesize (diameter*) 1asingle lesion, <0.5 cm 1bmultiple lesions, largest <0.5 cm 2asingle lesion <1.0 cm 2bmultiple lesions, largest <1.0 cm 3asingle lesion, ≤2.0 cm 3bmultiple lesions, largest ≤2.0 cm 4asingle lesion >2.0 cm 4bmultiple lesions, largest >2.0 cm *lesion size measured as the largest diameter gradeseverity 1asymptomatic 2mild 3moderate 4severe osteonecrosis of the jaw is classified based on severity, number of lesions, and lesion size. osteonecrosis of greater severity is given a higher grade, with asymptomatic onj designated as grade 1 and severe onj as grade 4. treatment the treatment should be tailored to the cause involved and the severity of the disease process. with oral osteoporosis, the emphasis should be on good nutrient absorption and metabolic wastes elimination through a healthy gastro-intestinal function, effective hepatic metabolism of toxicants such as exogenous estrogens, endogenous acetaldehyde and heavy metals, a balanced diet, healthy lifestyle, assessment of factors related to potential coagulopathies, and treatment of periodontal diseases and other oral and dental infections. in cases of advanced oral ischaemic osteoporosis and/or onj that are not bisphosphonates related, clinical evidence has shown that surgically removing the damaged marrow, usually by curettage and decortication, will eliminate the problem (and the pain) in 74% of patients with jaw involvement. repeat surgeries, usually smaller procedures than the first, may be required. almost a third of jawbone patients will need surgery in one or more other parts of the jaws because the disease so frequently present multiple lesions, i.e., multiple sites in the same or similar bones, with normal marrow in between. in the hip, at least half of all patients will get the disease in the opposite hip over time; this pattern occurs in the jaws as well. recently, it has been found that some osteonecrosis patients respond to anticoagulation therapies alone. the earlier the diagnosis the better the prognosis. research is ongoing on other non-surgical therapeutic modalities that could alone or in combination with surgery further improve the prognosis and reduce the morbidity of onj. a greater emphasis on minimizing or correcting known causes is necessary while further research is conducted on chronic ischaemic bone diseases such as oral osteoporosis and onj. in patients with bisphosphonates-associated onj, the response to surgical treatment is usually poor. conservative debridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this form of onj. although an effective treatment for bisphosphonate-associated bone lesions has not yet been established, and this is unlikely to occur until this form of onj is better understood, there have been clinical reports of some improvement after 6 months or more of complete cessation of bisphosphonate therapy. history onj is not a new disease: around 1850, forms of "chemical osteomyelitis" resulting from environmental pollutants, such as lead and the white phosphorus used in early (non-safety) matches (phossy jaw), as well as from popular medications containing mercury, arsenic or bismuth, were reported in the literature. this disease apparently did not often occur in individuals with good gingival health, and usually targeted the mandible first. it was associated with localized or generalized deep ache or pain, often of multiple jawbone sites. the teeth often appeared sound and suppuration was not present. even so, the dentist often began extracting one tooth after another in the region of pain, often with temporary relief but usually to no real effect. today a growing body of scientific evidence indicates that this disease process, in the cancellous bone and bone marrow, is caused by bone infarcts mediated by a range of local and systemic factors. bone infarcts as well as damage to the deeper portion of the cancellous bone is an insidious process. it is certainly not visible clinically and routine imaging techniques such as radiographs are not effective for that sort of damage. "an important and often incompletely understood principle of radiography is the amount of bone destruction that goes undetected by routine x-rays procedures; this has been demonstrated by numerous investigators. destruction confined to the cancellous portion of the bone cannot be detected radiographically, as radiolucencies appear only when there is internal or external erosion or destruction of the bone cortex." in fact no radiographic findings are specific for bone infarction / osteonecrosis. a variety of pathologies may mimic bone infarction, including stress fractures, infections, inflammations, and metabolic and neoplastic processes. the limitations apply to all imaging modalities, including plain radiography, radionuclide studies, ct scans, and magnetic resonance imaging (mri). through-transmission alveolar ultrasound, based on quantitative ultrasound (qus) in combination with panoramic dental radiography (orthopantomography) is helpful in assessing changes in jawbone density. when practitioners have an up-to-date understanding of the disease process and a good medical history is combined with detailed clinical findings, the diagnosis, with the help of various imaging modalities, can be achieved earlier in most patients. in the modern dental profession, it is only recently, when severe cases associated with bisphosphonates came to light, that the issue of onj has been brought to the attention of a majority of dentists. at present, the focus is mostly on bisphosphonate-associated cases, and is sometimes referred to colloquially as "phossy jaw", a similar, earlier occupational disease. however, the pharmaceutical manufacturers of bisphosphonates drugs such as merck and novartis have stated that onj in patients on this class of drug, can be related to a pre-existing condition, coagulopathy, anemia, infection, use of corticosteroids, alcoholism and other conditions already known to be associated with onj in the absence of bisphosphonate therapy. the implication is that bisphosphonates may not be the initiating cause of onj and that other pre-existing or concurrent systemic and/or local dental factors are involved. since onj has been diagnosed in many patients who did not take bisphosphonates, it is thus logical to assume that bisphosphonates are not the only factor in onj. while the oversuppression of bone turnover seems to play a major role in aggravating the disease process, other factors can and do initiate the pathophysiological mechanisms responsible for onj. in non-bisphosphonate cases of onj, it is mainly the cancellous portion of the bone and its marrow content that are involved in the disease process. the first stage is an oedema of the bone marrow initiated by a bone infarct, which is itself modulated by numerous causes, leading to myelofibrosis as a result of hypoxia and gradual loss of bone density characteristic of ischaemic osteoporosis. further deterioration can be triggered by additional bone infarcts leading to anoxia and localized areas of osteonecrosis within the osteoporotic cancellous bone. secondary events such as dental infection, injection of local anaesthetics with vasoconstrictors, such as epinephrine, and trauma can add further complications to the disease process and chronic non-pus forming bone infection osteomyelitis can also be associated with onj. however, in patients on bisphosphonates, the cortical bone is frequently involved as well. spontaneous exposure of necrotic bone tissue through the oral soft tissues or following non-healing bone exposure after routine dental surgery, characteristics of this form of onj, may be the result of late diagnosis of a disease process that has been masked by the oversuppression of osteoclastic activity, allowing pre-existing factors to further aggravate bone damage.