Osteonecrosis of the jaw ( ONJ ) is a severe bone disease (osteonecrosis) affecting the jaw (upper jaw and lower jaw). The various forms of ONJ have been described for the last 160 years, and a number of causes have been suggested in the literature.
Jaw osteonecrosis associated with bisphosphonate therapy, required by some cancer treatment regimens, has been identified and defined as a pathological entity (osteonecrosis-associated bisphosphonate in the jaw) since 2003. Possible risk of lower oral doses of bisphosphonates, taken by the patient to prevent or treating osteoporosis, remains uncertain.
Treatment options have been explored; however, a severe case of ONJ still requires surgical removal of the affected bone. Anamnesis and thorough assessment of pre-existing systemic problems and possible location of dental infection is needed to help prevent the condition, especially if bisphosphonate therapy is considered.
Video Osteonecrosis of the jaw
Signs and symptoms
The ONJ definitive symptom is the exposure of the mandibular or maxillary bone through a gingival lesion that does not heal. Pain, inflammation of the surrounding soft tissues, secondary infection or drainage may or may not be present. The development of lesions most commonly occurs after invasive dental procedures, such as extraction, and is also known to occur spontaneously. There may be no symptoms for weeks or months, until an open bone lesion appears. Lesions are more common in the mandible than the maxilla.
- Pain and neuropathy
- Erythema and suppuration
- Bad breath
Post-radiation osteonecrosis of the maxillary bone is something more common in the mandible (mandible) than the maxilla (maxilla) because there are more blood vessels in the lower jaw.
These symptoms are very similar to MRONJ symptoms. Patients experience a lot of pain, the area can swell, bone can be seen and fractures can occur. Patients may also have dry mouth and difficulty clearing their mouths. A patient who has osteonecrosis may also be susceptible to bacterial and fungal infections.
Osteoblasts, which form bone tissue are destroyed because of significant radiation causing increased osteoclast activity.
This condition can not be treated with antibiotics because there is no blood supply to the bone, making it difficult for antibiotics to reach potential infections.
This condition makes eating and drinking extremely difficult, and surgical management to remove necrotic bone improves circulation and reduces microorganisms.
Maps Osteonecrosis of the jaw
Cause
Toxic agents
Other factors such as toxins can adversely affect bone cells. Infections, chronic or acute, can affect blood flow by inducing platelet activation and aggregation, contributing to excessive coagulability (hypercoagulability) that may contribute to the formation of blood clots (thrombosis), the cause of bone infarction and known ischemia. Exogenous estrogens, also called hormonal disorders, have been associated with an increased tendency to clot (thrombophilia) and bone healing disorders.
Heavy metals such as lead and cadmium have been implicated in osteoporosis. Cadmium and lead increase the synthesis of plasminogen activator inhibitor-1 (PAI-1) which is the major inhibitor of fibrinolysis (the mechanism by which the body breaks freezing) and is shown to be the cause of hypofibrinolysis. Continuous blood clots can cause congestive blood flow (hyperemia) in the bone marrow, disruption of blood flow and ischemia in bone tissue resulting in lack of oxygen (hypoxia), bone cell damage and eventual cell death (apoptosis). Significance is the fact that the average concentration of cadmium in human bones in the 20th century has increased to about 10 times above the pre-industrial level.
Bisphosphonate
The first three cases of jaw-related bisphosphonate osteonecrosis were spontaneously reported to the FDA by oral surgeons in 2002, with toxicities described as potentially late-potentially toxic chemotherapy. In 2003 and 2004, three oral surgeons independently reported FDA information in 104 cancer patients with jaw-related bisphosphonate osteonecrosis seen in their referral practices in California, Florida, and New York. This case series is published as an article reviewed by colleagues in the Journal of Oral and Maxillofacial Surgery and one in the Journal of Clinical Oncology . Furthermore, many examples of people with ADR are reported to manufacturers and FDA. As of December 2006, 3607 cases of people with ADR have been reported to the FDA and 2227 cases have been reported to intravenous bisphosphonate manufacturers.
The Myeloma Foundation International web-based survey included 1203 respondents, 904 patients with myeloma and 299 with breast cancer and an estimate that after 36 months, jaw osteonecrosis has been diagnosed in 10% of 211 patients on zoledronate and 4% of 413 in pamidronate. A population-based study in Germany identified more than 300 cases of jaw osteonecrosis, 97% occurring in cancer patients (in high dose intravenous bisphosphonates) and 3 cases in 780,000 patients with osteoporosis for an incidence of 0.00038%. The time to the event ranges from 23-39 months and 42-46 months with intravenous bisphosphonates and high-dose oral. A prospective population-based study by Mavrokokki et al. . estimated incidence of jaw osteonecrosis 1.15% for intravenous bisphosphonates and 0.04% for oral bisphosphonates. Most cases (73%) were precipitated by tooth extraction. In contrast, producer-sponsored safety studies reported biphosphonate osteonecrosis associated with much lower jaw levels.
Although the majority of ONJ cases have occurred in cancer patients receiving high doses of intravenous bisphosphonates, nearly 800 cases have been reported in oral bisphosphonate users for osteoporosis or Paget's disease. In terms of severity the majority of ONJ cases in oral bisphosphonate users are stage 1-2 and tend to progress to resolution with conservative measures such as oral chlorhexidine rinse.
Because of the insertion of bisphosphonate drugs in bone tissue, the risk for BRONJ is high even after discontinuing drug administration for several years.
This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of reduction of bone turnover. However, bone health requires little more than just BMD. There are many other factors to consider.
In healthy bone tissue there is homeostasis between bone resorption and bone resorption. Diseased or damaged bones are resorbed through the osteoclast mediation process while the osteoblasts form new bones to replace them, thus maintaining healthy bone density. This process is commonly called remodeling.
However, osteoporosis is basically the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to the various causes and contributing factors, and bisphosphonates do not address these factors altogether.
In 2011, a proposal that incorporated reduced bone turnover and elements of infection from previous theories has been put forward. This cites the function of the affected macrophage disorder as the dominant factor in the development of ONJ.
In a systematic review of ONJ-related bisphosphonate cases until 2006, it was concluded that the mandible was more commonly affected than the maxilla (ratio 2: 1), and 60% of cases were preceded by dental surgical procedures. According to Woo, Hellstein and Kalmar, the oversuppression of bone turnover may be the primary mechanism for the development of ONJ forms, although there may be contributing co-morbid factors (as discussed elsewhere in this article). It is recommended that all potential jaw infection sites should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the need for subsequent dentoalveolar surgery. The risk of osteonecrosis in patients taking oral bisphosphonates, such as alendronate (Fosamax), for osteoporosis is uncertain and requires careful monitoring. Patients taking dexamethasone and other glucocorticoids are at higher risk.
The metalloproteinase 2 matrix may be a candidate gene for osteonecrosis of the jaw-related bisphosphonate, as this is the only gene known to be associated with bone abnormalities and atrial fibrillation, both of which are bisphosphonate side effects.
Pathophysiology
Histopathological changes
People with ONJ may have bone necrosis or bone marrow that is slowly strangled or malnourished. Bones with chronic blood flow poorly develop both fibrous marrow because the fibers can more easily live in areas of starvation of nutrients, oily, dead (wet decomposing) marrow, very dry, sometimes rough marrow (dry rot), or marrow really, true hollow space (osteocavitation), also typical ONJ. Blood flow disorders occur after bone infarction, blood clots formed in blood vessels smaller than the cancellous bone tissue.
Under ischemic conditions, many pathological changes in bone marrow and oral cancellous trabeculae have been documented. Microscopically, areas of "fatigue and/or necrotizing" degrees of fat and/or necrosis are evident, often with the fat collected from the crushed adipose cells (oil cyst) and with marrow fibrosis (reticular fat degeneration) seen. This change is present even if most bone trabeculae appear at first glance proper, mature and normal, but closer examination indicates the loss of osteocytes and variable microstructural cracks (splitting along the cleavage cleavage naturally).The microscopic features are similar to those of osteonecrosis ischemic or aseptic long bones, corticosteroid-induced osteonecrosis, and osteomyelitis caisson disease (deep-sea diver's) ".
In the cancellous part of the femoral head it is not uncommon to find trabeculae with seemingly intact osteocytes that seem "alive" but no longer synthesize collagen. This appears to be consistent with findings in the cancellous alveolar bone.
Osteonecrosis can affect any bone, but the hips, knees, and jaws are most often involved. Pain can often be severe, especially if the teeth and/or trigeminal nerve branches are involved, but many patients do not experience pain, at least in the early stages. When severe facial pain is said to be caused by osteonecrosis, the term NICO, for neuralgia-induces osteonecrosis of the cavity, is sometimes used, but it is controversial and far from being fully understood.
ONJ, even in the form of lightness or lightness, creates a marrow environment conducive to bacterial growth. Because many individuals have low-grade dental and gum infections, this may be one of the major mechanisms that cause the problem of increasingly severe marrow flow; Local infections/inflammation will cause increased pressure and freezing in the area involved. No other bone has this mechanism as a major risk factor for osteonecrosis. Various bacteria have been cultured from ONJ lesions. Typically, they are the same microorganisms as those found in periodontitis or dental devitalization. However, according to the special staining of the biopsied tissue, bacterial elements are rarely found in large quantities. Thus, while the ONJ is not primarily an infection, many cases have very low levels of secondary bacterial infections and chronic non-suppurative osteomyelitis can be attributed to ONJ. Fungal infections in the bone involved do not seem to be a problem, but viral infection has not been studied. Some viruses, such as smallpox virus (no longer in the wild) can produce osteonecrosis.
The effect of persistent ischemia on bone cells
The cortical bone is well vascularized by the surrounding soft tissues making it less susceptible to ischemic damage. Cancellous bones, with mesh-like structures and spaces filled with marrow tissue are more susceptible to damage by bone infarction, leading to Hypoxia (medical) and premature cell apoptosis. The mean lifespan of osteocytes has been estimated at 15 years in cancellous bone, and 25 years in cortical bone. while the average lifespan of human osteoclasts is about 2 to 6 weeks and the average lifespan of osteoblasts is about 3 months. In healthy bones these cells are constantly replaced by differentiation of bone marrow mesenchymal stem cells (MSC). However, in non-traumatic osteonecrosis and alcohol induced osteonecrosis of the femoral head, decreased ability of differentiation of the mesenchymal stem into bone cells has been demonstrated, and the changing osteoblastic function plays a role on the ON of the femoral head. If these results are extrapolated to ONJ, then the potential differentiation of mesenchymal bone marrow (MSC) cells coupled with altered osteoblastic activity and premature death of bone cells will explain the failure attempts at improvements seen in ischemic damaged canchemic bone tissue at ONJ..
The speed of premature cell death can occur depending on the cell type and degree and duration of anoxia. Hematopoietic cells, in the bone marrow, are sensitive to anoxia and are the first to die after a reduction or discharge of blood supply. In anoxic conditions they usually die within 12 hours. Experimental evidence suggests that bone cells consisting of osteocytes, osteoclasts, and osteoblasts die within 12-48 hours, and fatty marrow cells die within 120 hours. Bone death does not alter the radiographic opacity nor the mineral density. Necrotic bone does not undergo resorption; therefore, seems relatively more opaque.
An ischemic defective bone repair effort will usually occur in 2 phases. First, when the dead bone sounds live marrow, the capillaries and undifferentiated mesenchyme cells grow into the dead marrow space, while the macrophages lower the dead cells and dead fats. Second, mesenchymal cells differentiate into osteoblasts or fibroblasts. Under favorable conditions, new bone layers are formed on the surface of the bony trabeculae. If sufficiently thicken, these layers can decrease bone radiodensity; Therefore, the first radiographic evidence of previous osteonecrosis may be patchy sclerosis due to repair. Under unfavorable conditions, repeated attempts to improve ischemic conditions can be seen histologically and characterized by extensive delamination or microcracking along cement lines as well as the formation of excessive cement lines. The major failure of the repair mechanism due to persistent and repeated ischemic events is manifested as a trabecular fracture occurring in the dead bone under functional load. Then followed by cracks and crevices that cause structural collapse of the area involved (osteocavitation).
Diagnosis
Classification
Jaw osteonecrosis is classified by the severity, number of lesions, and size of the lesion. Higher osteonecrosis of severity is given higher values, with asymptomatic ONJs assigned as grade 1 and heavy ONJ as grade 4.
Treatment
Treatment should be tailored to the underlying cause and severity of the disease process. With oral osteoporosis the emphasis should be on good nutrient absorption and disposal of metabolic waste through healthy gastro-intestinal function, effective liver metabolism from toxins such as exogenous estrogens, endogenous acetaldehyde and heavy metals, balanced diet, healthy lifestyle, assessment of related factors for coagulopathy potential, and treatment of periodontal disease and other dental and oral infections.
In the case of advanced oral and/or non-bisphosphonated ischemic oral osteoporosis, clinical evidence has shown that surgery removing damaged marrow, usually with curettage and decortication, will remove the problem (and pain) in 74% of patients with involvement jaws. Repeat the operation, usually a procedure smaller than the first, may be required. Nearly a third of jawbone patients will require surgery on one or more other parts of the jaw because the disease often causes multiple lesions, ie, multiple sites in the same or similar bone, 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 jaw as well. Recently, it has been found that some osteonecrosis patients respond only to anticoagulation therapy. The earlier the diagnosis the better the prognosis. Ongoing studies on other non-surgical treatment modalities that may be alone or in combination with surgery further improve prognosis and reduce ONJ morbidity. A greater emphasis on minimizing or correcting known causes is needed while further research is conducted on chronic ischemic bone diseases such as oral osteoporosis and ONJ.
In patients with ONJ bisphosphonates, 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 preferred over aggressive surgical measures to treat ONJ forms. Although effective treatment for biphosphonate-related bone lesions has not been established, and this is unlikely to occur until this form of ONJ is better understood, there are clinical reports of some improvement after 6 months or more of complete cessation of bisphosphonate therapy..
History
ONJ is not a new disease: Approximately 1850 forms of "chemical osteomyelitis" resulting from environmental pollution, such as lead and white phosphorus used in early (unsafe) (Phossy jaw) games, as well as from popular drugs containing mercury, arsenic or bismuth , reported in the literature. This disease is apparently not common in individuals with good gingival health, and is usually targeted at the lower jaw first. It is associated with localized or generalized pain or pain, often from some jaw bone sites. His teeth often appear sound and pus not present. Even so, dentists often start taking one tooth one at a time in the pain area, often with temporary relief but usually have no real effect.
Today more and more scientific evidence suggests that the process of this disease, in cancellous bone and bone marrow, is caused by bone infarction mediated by various local and systemic factors. The infarct bone and damage to the deeper part of the cancellus bone is a dangerous process. This is certainly not seen clinically and routine imaging techniques such as radiography are not effective for such damage. "The radiographic principle that is important and often not fully understood is the amount of bone damage undetected by routine x-ray procedures, which has been demonstrated by many researchers." The limited damage to the cancellous bone can not be detected radiographically, since radiolucent only appears when there is an internal or external erosion or damage to the bone cortex. "In fact, no radiographic findings are specific to bone infarction/osteonecrosis. Pathologies may mimic bone infarction, including stress fractures, infections, inflammation, and metabolic and neoplastic processes. Limits apply to all imaging modalities, including plain radiography, radionuclide studies, CT scans, and magnetic resonance imaging (MRI). Through an alveolar ultrasound transmission, quantitative ultrasound (QUS) in combination with dor- panoramic dorphism (orthopantomography) is helpful in assessing changes in bone density of the jaw. When practitioners have a current understanding of the disease process and a good history combined with detailed clinical findings and series of events, the diagnosis, with the help of various imaging modalities, can be achieved early, in most patients.
In the modern dental profession, recently when the severe cases associated with bisphosphonates were revealed, that ONJ problems have been the concern of the majority of dentists. Currently, the focus is mostly on the associated bisphosphonate cases, and is sometimes referred to everyday language as "jaws," similar earlier work diseases. However, pharmaceutical manufacturers of bisphosphonates such as Merck and Novartis have stated that ONJ in patients in this class of drugs may be associated with pre-existing conditions, coagulopathy, anemia, infection, corticosteroid use, alcoholism and other known conditions associated with ONJ bisphosphonate therapy. The implication is that bisphosphonates may not be the original cause of ONJ and that other existing or simultaneous systemic and/or local factors are involved.
Because ONJ has been diagnosed in many patients who do not use bisphosphonates, it is logical to assume that bisphosphonates are not the only factor in ONJ. While oversuppression from bone turnover seems to play a major role in aggravating the disease process, other factors can and do initiate responsible pathophysiological mechanisms for ONJ. In the case of non-bisphosphonate ONJ, it is mainly the cancellous portion of the bone and its marrow content involved in the disease process. The first stage is bone marrow edema initiated by bone infarction, which itself is modulated by many causes, leading to myelofibrosis as a result of hypoxia and gradual loss of bone mineral density characteristics of ischemic osteoporosis. Further damage can be triggered by additional bone infarction leading to anoxia and localized osteonecrosis areas within the osteoporotic cancellous bone. Secondary occurrences such as dental infections, local anesthetic injection with vasoconstrictors, such as epinephrine, and trauma can add further complications to chronic disease processes and bone infections that do not cause osteomyelitis pus may also be associated with ONJ.
However, in patients with bisphosphonates, cortical bone is also often involved. Spontaneous exposure of necrotic bone tissue through the soft tissues of the mouth or after bone exposure that does not heal after routine dental surgery, this form of ONJ characteristic, may be the result of a final diagnosis of disease process that has been covered by osteoclastic oversupression. activity, allowing pre-existing causes to further aggravate bone damage.
References
External links
- Maxillofacial Education Center & amp; Research
Source of the article : Wikipedia
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