Medication-related osteonecrosis of the jaw

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Medication-related osteonecrosis of the jaw
Other namesMON of the jaw,
Medication-related osteonecrosis of the jaw (MRONJ),
Medication-induced osteonecrosis of the jaw (MIONJ),
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) (formerly)
Stage 2 MRONJ.jpg
Specialty Oral and maxillofacial surgery
Symptoms Exposed bone after extraction, pain
Complications Osteomyelitis of the jaw
Usual onsetAfter dental extractions
DurationVariable
TypesStage 1-Stage 3
CausesMedications related to cancer therapy, and osteoporosis in combination with dental surgery
Risk factors Duration of anti-resorptive or anti-angiogenic drugs, intravenous vs by-mouth
Diagnostic method Exposed bone >8 weeks
Differential diagnosis Osteomyelitis, Osteoradionecrosis
PreventionNo definitive. Drug holiday for some patients.
Treatmentantibacterial rinses, antibiotics, removal exposed bone
Prognosis good
Frequency0.2% for those on biphosphonate type drugs >4 years

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 following oral and maxillofacial surgery, periodontal surgery, or endodontic therapy. [1]

Contents

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 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. [2] [3] [4] [5] Osteonecrotic complications associated with denosumab, another antiresorptive drug from a different drug category, were soon determined to be related to this condition. Newer medications such as anti-angiogenic 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. [4]

There is no known prevention for bisphosphonate-associated osteonecrosis of the jaw. [6] 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 cancers. 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). [7]

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. [8]

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. [7]

Osteonecrosis, or localized death of bone tissue, of the jaws, is a rare potential complication in cancer patients receiving treatments including radiation, chemotherapy, or in patients with tumors or infectious embolic events. In 2003, [9] [10] reports surfaced of the increased risk of osteonecrosis in patients receiving these therapies concomitant with intravenous bisphosphonate. [11] 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. [12]

In response to the growing base of literature on this association, the United States Food and Drug Administration issued a broad drug class warning of this complication for all bisphosphonates in 2005. [13]

Signs and symptoms

Two extraction sites in the same person on denosumab.
MRONJ 1st molar.jpg
Exposed bone upper right molar 10 weeks after tooth removal.
Well healed extraction socket.jpg
Well healed socket upper left molar 10 weeks after tooth removal.

Classically, MRONJ will cause an ulcer or areas of necrotic bone for weeks, months, or even years following a tooth extraction. [14] While the exposed, dead bone does not cause symptoms these areas often have mild pain from the inflammation of the surrounding tissues. [15] Clinical signs and symptoms associated with, but not limited to MRONJ, include:

Cause

Cases of MRONJ have also been associated with the use of the following two intravenous and three oral bisphosphonates, respectively: zoledronic acid and pamidronate and alendronate, risedronate, and ibandronate. [20] [21] 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. [22] 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

MRONJ: Duration of oral biphosphonate use vs risk of MRONJ MRONJ duration of oral biphosphonate vs risk graph.png
MRONJ: Duration of oral biphosphonate use vs risk of MRONJ

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. [6]

Although the total United States prescriptions for oral bisphosphonates exceeded 30 million in 2006, less than 10% of MRONJ cases were associated with patients taking oral bisphosphonate drugs. [23] 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. [24]

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. [25]

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. [8]

Risk factors include: [8]

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.’ [26]

Patient risk categories

Low: [8]

High:

"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." [8]

Anti-resorptive drugs

Anti-resorptive drugs inhibit osteoclast differentiation and function, slowing down the breakdown of bone. [27] They are usually prescribed for patients with osteoporosis or other metastatic bone diseases[ clarification needed ], such as Paget's disease, osteogenesis imperfecta and fibrous dysplasia. [28] [29]

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. [30]

  1. Bisphosphonate
    • Bisphosphonates are either administered orally or intravenously. They reduce bone resorption. [31]
    • 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. [29] [31]
    • This type of drug has a high affinity for hydroxyapatite [28] and stays in bone tissue for a long period of time, [29] with alendronate, it has a half-life of approximately ten years. [30]
    • The risk of a patient having MRONJ after discontinuing this medication is unknown. [30]
    • There are suggestions that bisphosphonate may inhibit the proliferation of soft tissue cells and increases apoptosis. This may result in delayed soft tissue healing. [30]
    • Examples of bisphosphonates: : Zoledronic acid (Reclast, Zometa), Risedronate (Actonel), Alendronate (Fosamax), Etidronate (Didronel), Ibandronate (Boniva), Pamidronate (Aredia), Tiludronate (Skelid). [32]
  2. Denosumab
    • Denosumab is a monoclonal antibody [33] [34] which is administrated subcutaneously. It inhibits osteoclast differentiation and activation, reduces bone resorption, improves bone density and lessens skeletal-related events associated with metastasis. [31]
    • Mechanism of action: The drug binds to receptor activator nuclear factor κB ligand (RANKL), preventing the interaction with RANK. [33] [31] [34]
    • It does not bind to bone and its effect on bone diminishes in 9 months. [30]

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. [8]

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. [35] They prevent the tumour from growing. For example, bevacizumab/aflibercept 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. [36] Sunitinib is a different example of an anti-angiogenic drug; it inhibits cellular signalling by targeting multiple receptor tyrosine kinases. It reduces the blood supply to the tumour by inhibiting new blood vessel formation in the tumor. [37] The tumour may stop growing or even shrink. [38]

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 differentiation and function, precipitated by drug therapy, leads to decreased bone resorption and remodelling. [31] [39] Evidence also suggests bisphosphonates induce apoptosis of osteoclasts. [40] Another suggested factor is inhibition of angiogenesis due to bisphosphonates; this effect remains uncertain. [41] [42] [43] Several studies have proposed that bisphosphonates cause excessive reduction of bone turnover, resulting in a higher risk of bone necrosis when repair is needed. [44] [45] [46]

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[ clarification needed ] needed for bone resorption does not form. [7] 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[ clarification needed ].

Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol. Osteoclast.jpg
Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.

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. [13]

Diagnosis

A diagnosis of bisphosphonate-associated osteonecrosis of the jaw relies on three criteria: [6]

  1. the patient possesses an area of exposed bone in the jaw persisting for more than 8 weeks,
  2. the patient must present with no history of radiation therapy to the head and neck
  3. 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 of and the length of exposure to bisphosphonates are linked to the risk of developing bisphosphonate-associated osteonecrosis of the jaw. [47]

In the 2014 AAOMS update [7] on MRONJ, a staging and treatment strategies table was created:

Staging and Treatment Strategies [7] [48] *Exposed or probable bone in the maxillofacial region without resolution for greater than 8 weeks in patients treated with an antiresorptive and/or an antiangiogenic agent who have not received radiation therapy to the jaws.
**Regardless of the disease stage, mobile segments of bony sequestrum should be removed without exposing uninvolved bone. The extraction of symptomatic teeth within exposed, necrotic bone should be considered since it is unlikely that the extraction will exacerbate the established necrotic process.
MRONJ StagingCriteria* (>8 weeks)Treatment Strategies**Picture
At riskNo apparent necrotic bone in patients who have been treated with either oral or IV bisphosphonatesNo treatment indicated, Patient educationN/A
Stage 0No clinical evidence of necrotic bone, but non-specific clinical findings, radiographic changes and symptomsSystemic management, including the use of pain medication and antibioticsN/A
Stage 1Exposed and necrotic bone, or fistulae that probes to bone, in patients who are asymptomatic and have no evidence of infectionAntibacterial mouth rinse, Clinical follow-up on a quarterly basis, Patient education and review of indications for continued bisphosphonate therapy Stage 1 MRONJ.jpg
Stage 2Exposed and necrotic bone, or fistulae that probes to bone, associated with infection as evidenced by pain and erythema in the region of the exposed bone with or without purulent drainageSymptomatic treatment with oral antibiotics, Oral antibacterial mouth rinse, Pain control, Debridement to relieve soft tissue irritation and infection control Stage 2 MRONJ.jpg
Stage 3Exposed and necrotic bone or a fistula that probes to bone in patients with pain, infection, and one or more of the following: exposed and necrotic bone extending beyond the region of alveolar bone,(i.e., inferior border and ramus in the mandible, maxillary sinus and zygoma in the maxilla) resulting in pathologic fracture, extra-oral fistula, oral antral/oral nasal communication, or osteolysis extending to the inferior border of the mandible of sinus floorAntibacterial mouth rinse, Antibiotic therapy and pain control, Surgical debridement/resection for longer term palliation of infection and pain Stage 3 MRONJ.jpg
Mandibular fistula.jpg

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. [7] 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. [49]

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. [50] 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. [51]

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

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 and/or metronidazole.

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. [54]

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. [55]

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. [8]

In patients taking oral drugs for osteoporosis, the likelihood of MRONJ development varies from 0 - 0.2%. [7]

See also

Related Research Articles

Phossy jaw, formally known as phosphorus necrosis of the jaw, was an occupational disease affecting those who worked with white phosphorus without proper safeguards. It is also likely to occur as the result of use of banned chemical weapons that contain white phosphorus. It was most commonly seen in workers in the matchstick industry in the 19th and early 20th centuries. It was caused by white phosphorus vapor, which destroys the bones of the jaw. Modern occupational hygiene practices have since eliminated the working conditions that caused this disease.

<span class="mw-page-title-main">Bisphosphonate</span> Pharmaceutical drugs for preventing bone loss

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 have two phosphonate groups. They are thus also called diphosphonates.

<span class="mw-page-title-main">Paget's disease of bone</span> Disease affecting bone remodeling

Paget's disease of bone is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture or arthritis of associated joints.

<span class="mw-page-title-main">Alendronic acid</span> Chemical compound

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 supplementation, and lifestyle changes.

<span class="mw-page-title-main">Dental implant</span> Surgical component that interfaces with the bone of the jaw

A dental implant is a prosthesis that interfaces with the bone of the jaw or skull to support a dental prosthesis such as a crown, bridge, denture, or facial prosthesis or to act as an orthodontic anchor. The basis for modern dental implants is a biological process called osseointegration, in which materials such as titanium or zirconia form an intimate bond to the bone. The implant fixture is first placed so that it is likely to osseointegrate, then a dental prosthetic is added. A variable amount of healing time is required for osseointegration before either the dental prosthetic is attached to the implant or an abutment is placed which will hold a dental prosthetic/crown.

<span class="mw-page-title-main">Zoledronic acid</span> Chemical compound

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 to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.

<span class="mw-page-title-main">Orthognathic surgery</span> Surgery of the jaw

Orthognathic surgery, also known as corrective jaw surgery or simply jaw surgery, is surgery designed to correct conditions of the jaw and lower face related to structure, growth, airway issues including sleep apnea, TMJ disorders, malocclusion problems primarily arising from skeletal disharmonies, and other orthodontic dental bite problems that cannot be treated easily with braces, as well as the broad range of facial imbalances, disharmonies, asymmetries, and malproportions where correction may be considered to improve facial aesthetics and self-esteem.

<span class="mw-page-title-main">Dental extraction</span> Operation to remove a tooth

A dental extraction is the removal of teeth from the dental alveolus (socket) in the alveolar bone. Extractions are performed for a wide variety of reasons, but most commonly to remove teeth which have become unrestorable through tooth decay, periodontal disease, or dental trauma, especially when they are associated with toothache. Sometimes impacted wisdom teeth cause recurrent infections of the gum (pericoronitis), and may be removed when other conservative treatments have failed. In orthodontics, if the teeth are crowded, healthy teeth may be extracted to create space so the rest of the teeth can be straightened.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Ibandronic acid</span> Chemical compound

Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer. It may also be used to treat hypercalcemia. It is typically formulated as its sodium salt ibandronate sodium.

<span class="mw-page-title-main">Osteonecrosis of the jaw</span> Medical condition

Osteonecrosis of the jaw (ONJ) is a severe bone disease (osteonecrosis) that affects the jaws. Various forms of ONJ have been described since 1861, and a number of causes have been suggested in the literature.

<span class="mw-page-title-main">Denosumab</span> Human monoclonal antibody

Denosumab is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

Neuralgia-inducing cavitational osteonecrosis (NICO) is a diagnosis whereby a putative jawbone cavitation causes chronic facial neuralgia; this is different from osteonecrosis of the jaw. In NICO the pain is said to result from the degenerating nerve ("neuralagia"). The condition is probably rare, if it does exist.

<span class="mw-page-title-main">Bone metastasis</span> Medical condition

Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing sarcoma are rare; the most common bone tumor is a metastasis. Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

<span class="mw-page-title-main">C-terminal telopeptide</span> Chemical compound

The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is the C-terminal telopeptide of fibrillar collagens such as collagen type I and type II. It is used as a biomarker in the serum to measure the rate of bone turnover. It can be useful in assisting clinicians to determine a patient's nonsurgical treatment response as well as evaluate a patient's risk of developing complications during healing following surgical intervention. The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to bone resorption than any other test currently available.

<span class="mw-page-title-main">Osteoradionecrosis</span> Osteoradionecrosis is an Acute form of Osteomyelitis

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 years after radiation. Common signs and symptoms include pain, difficulty chewing, trismus, mouth-to-skin fistulas and non-healing ulcers.

<span class="mw-page-title-main">Osteolytic lesion</span>

An osteolytic lesion is a softened section of a patient's bone formed as a symptom of specific diseases, including breast cancer and multiple myeloma. This softened area appears as a hole on X-ray scans due to decreased bone density, although many other diseases are associated with this symptom. Osteolytic lesions can cause pain, increased risk of bone fracture, and spinal cord compression. These lesions can be treated using biophosphonates or radiation, though new solutions are being tested in clinical trials.

Oral manifestations of systematic disease are signs and symptoms of disease occurring elsewhere in the body detected in the oral cavity and oral secretions. High blood sugar can be detected by sampling saliva. Saliva sampling may be a non-invasive way to detect changes in the gut microbiome and changes in systemic disease. Another example is tertiary syphilis, where changes to teeth can occur. Syphilis infection can be associated with longitudinal furrows of the tongue.

<span class="mw-page-title-main">Discovery and development of bisphosphonates</span> Drugs used to treat bone disorders

Bisphosphonates are an important class of drugs originally commercialised in the mid to late 20th century. They are used for the treatment of osteoporosis and other bone disorders that cause bone fragility and diseases where bone resorption is excessive. Osteoporosis is common in post-menopausal women and patients in corticosteroid treatment where biphosphonates have been proven a valuable treatment and also used successfully against Paget's disease, myeloma, bone metastases and hypercalcemia. Bisphosphonates reduce breakdown of bones by inhibiting osteoclasts, they have a long history of use and today there are a few different types of bisphosphonate drugs on the market around the world.

Parish P. Sedghizadeh is a clinician-scientist, and a clinical and surgical oral and maxillofacial pathologist. He is a Professor of Clinical Dentistry, and Section Chair of Diagnostic Sciences in the Division of Periodontology, Diagnostic Sciences & Dental Hygiene at the Herman Ostrow School of Dentistry, University of Southern California. He is also the Director of the Oral Pathology and Radiology Distance Learning Program at the University of Southern California.

References

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  2. ↑ Marx RE (September 2003). "Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic". Journal of Oral and Maxillofacial Surgery. 61 (9): 1115–7. doi: 10.1016/s0278-2391(03)00720-1 . PMID   12966493.
  3. ↑ Migliorati CA (November 2003). "Bisphosphanates and oral cavity avascular bone necrosis". Journal of Clinical Oncology. 21 (22): 4253–4. doi: 10.1200/JCO.2003.99.132 . PMID   14615459.
  4. 1 2 Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F (October 2014). "American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update". Journal of Oral and Maxillofacial Surgery. 72 (10): 1938–56. doi:10.1016/j.joms.2014.04.031. PMID   25234529.
  5. ↑ Sigua-Rodriguez EA, da Costa Ribeiro R, de Brito AC, Alvarez-Pinzon N, de Albergaria-Barbosa JR (2014). "Bisphosphonate-related osteonecrosis of the jaw: a review of the literature". International Journal of Dentistry. 2014: 192320. doi: 10.1155/2014/192320 . PMC   4020455 . PMID   24868206.
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  8. 1 2 3 4 5 6 7 "Oral Health Management of Patients at Risk of Medication-related Osteonecrosis of the Jaw" (PDF). Scottish Dental Clinical Effectiveness Programme. March 2017.
  9. ↑ Marx RE (September 2003). "Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic". Journal of Oral and Maxillofacial Surgery. 61 (9): 1115–7. doi: 10.1016/S0278-2391(03)00720-1 . PMID   12966493.
  10. ↑ Migliorati CA (November 2003). "Bisphosphanates and oral cavity avascular bone necrosis". Journal of Clinical Oncology. 21 (22): 4253–4. doi: 10.1200/JCO.2003.99.132 . PMID   14615459.
  11. ↑ Appendix 11: Expert Panel Recommendation for the Prevention, Diagnosis and Treatment of Osteonecrosis of the Jaw
  12. ↑ Lehrer S, Montazem A, Ramanathan L, Pessin-Minsley M, Pfail J, Stock RG, Kogan R (January 2009). "Bisphosphonate-induced osteonecrosis of the jaws, bone markers, and a hypothesized candidate gene". Journal of Oral and Maxillofacial Surgery. 67 (1): 159–61. doi:10.1016/j.joms.2008.09.015. PMID   19070762.
  13. 1 2 Ruggiero SL (March 2008). "Bisphosphonate-related Osteonecrosis of the Jaws". Compendium of Continuing Education in Dentistry. 29 (2): 97–105. PMID   18429424.
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