bisphosphonate-related osteonecrosis of the jaw
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Medication-related osteonecrosis of the jaw (MON, MRONJ) is progressive death of the jawbone in a person exposed to a medication known to increase the risk of disease, in the absence of a previous radiation treatment. It may lead to surgical complication in the form of impaired
wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
following oral and maxillofacial surgery, periodontal surgery, or
endodontic therapy Root canal treatment (also known as endodontic therapy, endodontic treatment, or root canal therapy) is a treatment sequence for the infected pulp of a tooth which is intended to result in the elimination of infection and the protection o ...
. Particular medications can result in MRONJ, a serious but uncommon side effect in certain individuals. Such medications are frequently used to treat diseases that cause bone resorption such as osteoporosis, or to treat cancer. The main groups of drugs involved are anti-resorptive drugs, and anti-angiogenic drugs. This condition was previously known as bisphosphonate-related
osteonecrosis Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Co ...
of the jaw (BON or BRONJ) because osteonecrosis of the jaw correlating with bisphosphonate treatment was frequently encountered, with its first incident occurring in 2003. Osteonecrotic complications associated with
denosumab Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone. Denosumab is contraindicated in people with low blood calci ...
, another antiresorptive drug from a different drug category, were soon determined to be related to this condition. Newer medications such as anti-
angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...
drugs have been potentially implicated causing a very similar condition and consensus shifted to refer to the related conditions as MRONJ; however, this has not been definitively demonstrated. There is no known prevention for bisphosphonate-associated osteonecrosis of the jaw.''Osteoporosis medications and your dental health'' pamphlet #W418, American Dental Association/ National Osteoporosis Foundation, 2008 Avoiding the use of bisphosphonates is not a viable preventive strategy on a general-population basis because the medications are beneficial in the treatment and prevention of osteoporosis (including prevention of bony fractures) and treatment of
bone cancer A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thy ...
s. Current recommendations are for a 2-month drug holiday prior to dental surgery for those who are at risk (intravenous drug therapy, greater than 4 years of by-mouth drug therapy, other factors that increase risk such as steroid therapy). It usually develops after dental treatments involving exposure of bone or trauma, but may arise spontaneously. Patients who develop MRONJ may experience prolonged healing, pain, swelling, infection and exposed bone after dental procedures, though some patients may have no signs/symptoms.


Definition

According to the updated 2014 AAOMS position paper (modified from 2009), in order to distinguish MRONJ, the working definition claims patients may be considered to have MRONJ if all the following characteristics are present: :1. Current or previous treatment with antiresorptive or antiangiogenic agents. :2. Exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for longer than 8 weeks. :3. No history of radiation therapy to the jaws or obvious metastatic disease to the jaws.
Osteonecrosis Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Co ...
, or localized death of
bone tissue A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, a ...
, of the
jaw The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term ''jaws'' is also broadly applied to the whole of the structures constituting the vault of the mouth and serv ...
s, is a rare potential complication in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
patients receiving treatments including radiation,
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
, or in patients with
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s or infectious
emboli An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule ( fat embolism), a bubble of air or other gas (gas embolism), amniotic fluid ( amni ...
c events. In 2003, reports surfaced of the increased risk of osteonecrosis in patients receiving these therapies concomitant with intravenous
bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
. Matrix metalloproteinase-2 may be a candidate gene for bisphosphonate-associated osteonecrosis of the jaws, since it is the only gene known to be associated with both bone abnormalities and atrial fibrillation, another side effect of bisphosphonates. In response to the growing base of literature on this association, the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
issued a broad drug class warning of this complication for all bisphosphonates in 2005.


Signs and symptoms

Classically, MRONJ will cause an ulcer or areas of necrotic bone for weeks, months, or even years following a tooth extraction. While the exposed, dead bone does not cause symptoms these areas often have mild pain from the inflammation of the surrounding tissues. Clinical signs and symptoms associated with, but not limited to MRONJ, include: *Jaw pain and neuropathy *Loose teeth *Mucosal swelling *
Erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
*
Suppuration Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
*Soft tissue
ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
persisting for more than 8 weeks *
Trismus Trismus, commonly called ''lockjaw'' as associated with tetanus, is a condition of limited jaw mobility. It may be caused by spasm of the muscles of mastication or a variety of other causes. Temporary trismus occurs much more frequently than perma ...
*Non-healing extraction sockets *
Paraesthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
or numbness in the jaw *
Bad breath Bad breath, also known as halitosis, is a symptom in which a noticeably unpleasant breath odour is present. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder. Th ...
*Exposed necrotic jaw bone


Cause

Cases of MRONJ have also been associated with the use of the following two intravenous and three oral bisphosphonates, respectively:
zoledronic acid Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due ...
and
pamidronate Pamidronic acid or pamidronate disodium or APD (marketed as Aredia among others), is a nitrogen-containing bisphosphonate used to prevent osteoporosis. It was patented in 1971 and approved for medical use in 1987. Medical uses It is used to pre ...
and
alendronate Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementati ...
,
risedronate Risedronic acid, often used as its sodium salt risedronate sodium, is a bisphosphonate. It slows down the cells which break down bone. It's used to treat or prevent osteoporosis, and treat Paget's disease of bone. It is taken by mouth. It was pa ...
, and ibandronate. Despite the fact that it remains vague as to what the actual cause is, scientists and doctors believe that there is a correlation between the necrosis of the jaw and time of exposure to bisphosphonates. Causes are also thought to be related to bone injury in patients using bisphosphonates as stated by Remy H Blanchaert in an article about the matter.


Risk factors

The overwhelming majority of MRONJ diagnoses, however, were associated with intravenous administration of bisphosphonates (94%). Only the remaining 6% of cases arose in patients taking bisphosphonates orally. Although the total
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prescriptions for oral bisphosphonates exceeded 30 million in 2006, less than 10% of MRONJ cases were associated with patients taking oral bisphosphonate drugs. Studies have estimated that BRONJ occurs in roughly 20% of patients taking intravenous zoledronic acid for cancer therapy and in between 0–0.04% of patients taking orally administered bisphosphonates. Owing to prolonged embedding of bisphosphonate drugs in the bone tissues, the risk for MRONJ is elevated even after stopping the administration of the medication for several years. Patients who stopped taking anti-angiogenic drugs are exposed to the same risk as patients who have never taken the drugs because anti-angiogenic drugs do not normally reside in the body for a long period of time. Risk factors include: * Dental treatment (e.g. dentoalveolar surgery/procedure that impacts bone) – it is possible for MRONJ to occur spontaneously without any recent invasive dental treatment * Duration of
bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
drug therapy – increased risk with increased cumulative dose of drug * Other concurrent medication – use of chronic systemic glucocorticoid increases risk when they are taken in combination with anti-resorptive drugs * Dental implants * Drug holidays – no evidence to support a reduction in MRONJ risk if patients stop taking bisphosphonates temporarily/permanently, as drugs can persist in skeletal tissues for many years * Treatment in the past with anti-resorptive/anti-angiogenic drugs * Patient being treated for cancer – higher risk * Patients being treated for osteoporosis/non-malignant bone diseases (e.g. Paget's disease) – lower risk


Research findings

‘The risk of MRONJ after dental extraction was significantly higher in patients treated with ARD (antiresorptive drugs) for oncological reasons (3.2%) than in those treated with ARD for OP (osteoporosis) (0.15%) (''p'' < 0.0001). Dental extraction performed with adjusted extraction protocols decreased MRONJ development significantly. Potential risk indicators such as concomitant medications and pre-existing osteomyelitis were identified.’


Patient risk categories

Low: * Treatment of osteoporosis or non-malignant bone disease with oral bisphosphonates for <5 years (not taking systemic glucocorticoids) * Treatment of osteoporosis or non-malignant bone disease with quarterly/yearly infusions of intravenous bisphosphonates for <5 years (not taking systemic glucocorticoids) * Treatment of osteoporosis or non-malignant bone disease with
denosumab Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone. Denosumab is contraindicated in people with low blood calci ...
(not taking systemic glucocorticoids) High: * Patients being treated for osteoporosis or non-malignant bone disease with oral bisphosphonates/quarterly or yearly infusions of intravenous bisphosphonates for >5 years * Patients being treated for osteoporosis or non-malignant bone disease with bisphosphonates/denosumab for any length of time as well as being treated with systemic glucocorticoids * Patients being treated with anti-resorptive/anti-angiogenic drugs/both as part of cancer management * Previous MRONJ diagnosis ''"N.B. Patients who have taken bisphosphonate drugs at any time in the past and those who have taken denosumab in the last nine months are allocated to a risk group as if they are still taking the drug."''


Anti-resorptive drugs

Anti-resorptive drugs inhibit osteoclast differentiation and function, slowing down the breakdown of bone. They are usually prescribed for patients with osteoporosis or other metastatic bone diseases, such as Paget's disease, osteogenesis imperfecta and fibrous dysplasia. The two main types of anti-resorptive drugs are bisphosphonate and denosumab. These drugs help to decrease the risk of bone fracture and bone pain. Because the mandible has a faster remodeling rate compared to other bones in the body, it is more affected by the effects of these drugs. #
Bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
#* Bisphosphonates are either administrated orally or intravenously. They reduces bone resorption. #* Mechanism of action: Bisphosphonate binds to the mineral component of the bone and inhibits enzymes (i.e. farnesyl-pyrophosphate synthase) responsible for bone formation, osteoclast recruitment and osteoclast function. #* This type of drug has a high affinity for hydroxyapatite and stays in bone tissue for a long period of time, with alendronate, it has a half-life of approximately ten years. #* The risk of a patient having MRONJ after discontinuing this medication is unknown. #* There are suggestions that bisphosphonate may inhibit the proliferation of soft tissue cells and increases apoptosis. This may result in delayed soft tissue healing. #* Examples of bisphosphonates: : Zoledronic acid (Reclast, Zometa), Risedronate (Actonel), Alendronate (Fosamax), Etidronate (Didronel), Ibandronate (Boniva), Pamidronate (Aredia), Tiludronate (Skelid). #
Denosumab Denosumab (trade names Prolia and Xgeva) is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone. Denosumab is contraindicated in people with low blood calci ...
#* Denosumab is a monoclonal antibody which is administrated subcutaneously. It inhibits osteoclast differentiation and activation, reduces bone resorption, improves bone density and lessens skeletal-related events associated with metastasis. #* Mechanism of action: The drug binds to receptor activator nuclear factor κB ligand (RANKL), preventing the interaction with
RANK Rank is the relative position, value, worth, complexity, power, importance, authority, level, etc. of a person or object within a ranking, such as: Level or position in a hierarchical organization * Academic rank * Diplomatic rank * Hierarchy * ...
. #* It does not bind to bone and its effect on bone diminishes in 9 months.


Anti-angiogenic drugs

Osteonecrosis of the jaw has been identified as one of the possible complications of taking anti-angiogenic drugs; the association of the disease with the medication is known as MRONJ. This has been stated in the Drug Safety Updates by the MHRA. Angiogenesis inhibitors interfere with blood vessel formation by interfering with the angiogenesis signalling cascade. They are used primarily to treat cancer. These cancer-fighting agents tend to hinder the growth of blood vessels that supply the tumour, rather than killing tumour cells directly. They prevent the tumour from growing. For example, bevacizumab/
aflibercept Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the Europe ...
is a monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF), preventing VEGF from binding to receptors on the surface of normal endothelial cells. Sunitinib is a different example of an anti-angiogenic drug; it inhibits cellular signalling by targeting multiple receptor
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
s. It reduces the blood supply to the tumour by inhibiting new blood vessel formation in the tumor. The tumour may stop growing or even shrink.


Pathogenesis

Although the methods of action are not yet completely understood, it is hypothesized that medication-associated osteonecrosis of the jaw is related to a defect in jaw bone healing and remodelling. The inhibition of
osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
differentiation and function, precipitated by drug therapy, leads to decreased
bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...
and remodelling. Evidence also suggests bisphosphonates induce apoptosis of osteoclasts. Another suggested factor is inhibition of angiogenesis due to bisphosphonates; this effect remains uncertain. Several studies have proposed that bisphosphonates cause excessive reduction of bone turnover, resulting in a higher risk of bone necrosis when repair is needed. It is also thought that bisphosphonates bind to osteoclasts and interfere with the remodeling mechanism in bone. To be more specific, the drug interferes with the cholesterol biosynthesis pathway through the inhibition of farnesyl diphosphate synthase. Over time, the cytoskeleton of the osteoclasts loses its function and the essential border needed for bone resorption does not form. Like aminobisphosphonates, bisphosphonates have shown to have antiangiogenic properties. Therefore, effects include an overall decrease in bone recycling/turnover as well as an increased inhibition of the absorptive bone abilities. One theory is that because bisphosphonates are preferentially deposited in bone with high turnover, it is possible that the levels of bisphosphonate within the jaw are selectively elevated. To date, there have been no reported cases of bisphosphonate-associated complications within bones outside the craniofacial skeleton.


Diagnosis

A
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
of bisphosphonate-associated osteonecrosis of the jaw relies on three criteria: # the patient possesses an area of exposed bone in the jaw persisting for more than 8 weeks, # the patient must present with no history of
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
to the head and neck # the patient must be taking or have taken bisphosphonate medication. According to the updated 2009 BRONJ Position Paper published by the American Association of Oral and Maxillofacial Surgeons, both the
potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...
of and the length of exposure to bisphosphonates are linked to the
risk In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environm ...
of developing bisphosphonate-associated osteonecrosis of the jaw. In the 2014 AAOMS update on MRONJ, a staging and treatment strategies table was created:


Prevention

Tooth extraction is the major risk factor for development of MRONJ. Prevention including the maintenance of good oral hygiene, comprehensive dental examination and dental treatment including extraction of teeth of poor prognosis and dentoalveolar surgery should completed prior to commencing any medication which is likely to cause osteonecrosis (ONJ). Patients with removable prostheses should be examined for areas of mucosal irritation. Procedures which are likely to cause direct osseous trauma, e.g. tooth extraction, dental implants, complex restoration, deep root planning, should be avoided in preference of other dental treatments. There are limited data to support or refute the benefits of a drug holiday for osteoporotic patients receiving antiresorptive therapy. However, a theoretical benefit may still apply for those patients with extended exposure histories (>4 yr), and current recommendations are for a 2 month holiday for those at risk. There was low quality evidence suggesting taking antibiotics prior to the dental extraction, as well as the use of post operative techniques for wound closure lowered the risk of patients developing medication-related osteonecrosis of the jaw compared with the usual standard care received for regular dental extractions. Post operative wound closure has been suggested to prevent the contamination of the underlying bone. More evidence is needed to assess the use of antibiotics prior to treatment and the use of wound closure to prevent contamination of the bone, as the quality of evidence evaluated was low. Patients may be advised to limit alcohol consumption, stop smoking, and practice good dental hygiene. It is also advised for individuals who take bisphosphonates to never allow the tablet to dissolve in the mouth as this causes damage to the oral mucosa.


Management

Treatment usually involves antimicrobial mouth washes and oral antibiotics to help the immune system fight the attendant infection, and it also often involves local resection of the necrotic bone lesion. Many patients with MRONJ have successful outcomes after treatment, meaning that the local osteonecrosis is stopped, the infection is cleared, and the mucosa heals and once again covers the bone. The treatment the person receives depends on the severity of osteonecrosis of the jaw.


Conservative

Indicated in patients who have evidence of exposed bone but no evidence of infection. It may not necessarily eliminate all the lesions, but it may provide patients with long term relief. This approach involves a combination of antiseptic mouthwashes and analgesics and the use of
teriparatide Teriparatide, sold under the brand name Forteo, is a form of parathyroid hormone (PTH) consisting of the first ( N-terminus) 34 amino acids, which is the bioactive portion of the hormone. It is an effective anabolic (promoting bone formation) ag ...
. Splints may be used to protect sites of exposed necrotic bone.


Non-surgical

Indicated for people with exposed bone with symptoms of infection. This treatment modality may also be utilised for patients with other co-morbidities which precludes invasive surgical methods. This approach requires antimicrobial mouthwashes, systemic antibiotics and antifungal medication and analgesics.


Surgery

Surgical intervention is indicated in patients with symptomatic exposed bone with fistula formation and one or more of the following: exposed and necrotic bone extending beyond the alveolar bone resulting in pathological fracture; extra-oral fistula; oral antral communication or osteolysis extending from the inferior border of the mandible or the sinus floor. Surgical management involves necrotic bone resection, removal of loose sequestra of necrotic bone and reconstructive surgery. The objective of surgical management is to eliminate areas of exposed bone to prevent the risk of further inflammation and infection. The amount of surgical debridement required remains controversial.


Other

*
Hyperbaric oxygen therapy Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
*Ultrasonic therapy


Antibiotics

Antibiotics are used to treat cases involving infections. Penicillin is the first line of choice, although if this is contraindicated commonly used antimicrobials are: clindamycin,
fluoroquinolones A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...
and/or
metronidazole Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It i ...
. Intravenous antibiotics may be used if the infection resists oral treatment. However, there is little evidence of intravenous antibiotics being more efficacious than other methods of treatment.


Epidemiology

The likelihood of this condition developing varies widely from less than 1/10,000 to 1/100, as many other factors need to be considered, such as the type, dose and frequency of intake of drug, how long it has been taken for, and why it has been taken. In patients taking drugs for cancer, the likelihood of MRONJ development varies from 0 - 12%. This again, varies with the type of cancer, although prostate cancer and multiple myeloma are reported to be at a higher risk. In patients taking oral drugs for osteoporosis, the likelihood of MRONJ development varies from 0 - 0.2%.


See also

* C-terminal telopeptide, commonly known as CTX, a serum biomarker for bone turnover rate and a tool used to evaluate patient risk for complications due to BRONJ *
Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws (the maxilla and the mandible). Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature. Oste ...
, see section on Bisphosphonates *
Osteoradionecrosis Osteoradionecrosis (ORN) is a serious complication of radiation therapy in cancer treatment where radiated bone becomes necrotic and exposed. ORN occurs most commonly in the mouth during the treatment of head and neck cancer, and can arise over 5 y ...
, a term for osteonecrosis caused by radiotherapy *
Phossy jaw Phossy jaw, formally known as phosphorus necrosis of the jaw, was an occupational disease affecting those who worked with white phosphorus (also known as ''yellow phosphorus'') without proper safeguards. It was most commonly seen in workers in th ...


References


External links

{{Medical resources , DiseasesDB = , ICD10 = {{ICD10, K10.2 + {{ICD10, Y40-Y59 , ICD9 = , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = D059266 * https://web.archive.org/web/20120901140540/http://www.ada.org/sections/professionalResources/pdfs/topics_ARONJ_report.pdf Osteonecrosis Jaw disorders