Osteonecrosis of the jaw

Osteonecrosis of the jaws
Other names	Osteonecrosis of the mandible
Osteonecrosis of the jaw of the upper left jaw in a patient diagnosed with chronic venous insufficiency
Specialty	Rheumatology

Osteonecrosis of the jaw (ONJ) is a severe

Osteonecrosis of the jaw associated with

Treatment options have been explored; however, severe cases of ONJ still require surgical removal of the affected bone.[3] A thorough history and assessment of pre-existing systemic problems and possible sites of dental infection are required to help prevent the condition, especially if bisphosphonate therapy is considered.^[2]

Signs and symptoms

The definitive symptom of ONJ is the exposure of

• Pain and neuropathy^[6]
• Erythema and suppuration
• Bad breath

Post radiation maxillary bone osteonecrosis is something that is found more in the lower jaw (mandible) rather than the maxilla (upper jaw) this is because there are many more blood vessels in the upper jaw.^[7]

The symptoms of this are very similar to the symptoms of medication-related osteonecrosis of the jaw (MRONJ). Patients are in a lot of pain, the area may swell up, bone may be seen and fractures may take place. The patients may also have a dry mouth and find it difficult to keep their mouth clean. A patient that has osteonecrosis may also be susceptible to bacterial and fungal infections.^[8]

The osteoblasts, which form the bone tissue, are destroyed due to the radiation with increased activity of osteoclasts.^{[citation needed]}

This condition cannot be treated by antibiotics as there is no blood supply to the bone, making it difficult for the antibiotics to reach the potential infection.^{[citation needed]}

This condition makes eating and drinking very difficult, and surgical management removing the necrotic bone improves circulation and decreases microorganisms.^{[citation needed]}

Causes

Toxic agents

Other factors such as toxicants can adversely impact bone cells. Infections, chronic or acute, can affect blood flow by inducing platelet activation and aggregation, contributing to a localized state of excess coagulability (

The International Myeloma Foundation's web-based survey included 1203 respondents, 904 patients with myeloma and 299 with breast cancer and an estimate that after 36 months, osteonecrosis of the jaw had been diagnosed in 10% of 211 patients on zoledronate and 4% of 413 on pamidronate.^[16] A population based study in Germany identified more than 300 cases of osteonecrosis of the jaw, 97% occurring in cancer patients (on high-dose intravenous bisphosphonates) and 3 cases in 780,000 patients with osteoporosis for an incidence of 0.00038%. Time to event ranged from 23 to 39 months and 42–46 months with high dose intravenous and oral bisphosphonates.^[17] A prospective, population based study by Mavrokokki et al.. estimated an incidence of osteonecrosis of the jaw of 1.15% for intravenous bisphosphonates and 0.04% for oral bisphosphonates. Most cases (73%) were precipitated by dental extractions. In contrast, safety studies sponsored by the manufacturer reported bisphosphonate-associated osteonecrosis of the jaw rates that were much lower.^{[citation needed]}

Although the majority of cases of ONJ have occurred in cancer patients receiving high dose intravenous bisphosphonates, almost 800 cases have been reported in oral bisphosphonate users for osteoporosis or Pagets disease. In terms of severity most cases of ONJ in oral bisphosphonate users are stage 1–2 and tend to progress to resolution with conservative measures such as oral chlorhexidine rinses.^{[citation needed]}

Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for BRONJ is high even after stopping the administration of the medication for several years.^[18][19]

This form of therapy has been shown to prevent loss of bone mineral density (BMD) as a result of a reduction in bone turnover. However, bone health entails quite a bit more than just BMD. There are many other factors to consider.^{[citation needed]}

In healthy bone tissue there is a homeostasis between bone resorption and ossification. Diseased or damaged bone is resorbed through the osteoclasts mediated process while osteoblasts form new bone to replace it, thus maintaining healthy bone density. This process is commonly called remodelling.

However, osteoporosis is essentially the result of a lack of new bone formation in combination with bone resorption in reactive hyperemia, related to various causes and contributing factors, and bisphosphonates do not address these factors at all.

In 2011, a proposal incorporating both the reduced bone turnover and the infectious elements of previous theories has been put forward. It cites the impaired functionality of affected macrophages as the dominant factor in the development of ONJ.^[20]

In a systematic review of cases of bisphosphonate-associated ONJ up to 2006, it was concluded that the

Osteonecrosis can affect any bone, but the hips, knees and jaws are most often involved. Pain can often be severe, especially if teeth and/or a branch of the trigeminal nerve is involved, but many patients do not experience pain, at least in the earlier stages. When severe facial pain is purported to be caused by osteonecrosis, the term NICO, for neuralgia-inducing cavitational osteonecrosis, is sometimes used, but this is controversial and far from completely understood.^[26]

ONJ, even in its mild or minor forms, creates a marrow environment that is conducive to bacterial growth. Since many individuals have low-grade infections of the teeth and gums, this probably is one of the major mechanisms by which the marrow blood flow problem can worsen; any local infection /

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.^[3] 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.^[37] 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.^[38] Although an effective treatment for bisphosphonate-associated bone lesions has not yet been established,^[39] 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.^[40]

History

ONJ is not a new disease: around 1850, forms of "chemical osteomyelitis" resulting from environmental pollutants, such as lead and the

Today a growing body of scientific evidence indicates that this disease process, in the cancellous bone and bone marrow, is caused by bone

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.[51]^[52] 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.^[53][54]

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