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Of The Jaw "MRONJ"

Osteonecrosis

medication Related

NECROSIS

BONE

DEATH

Just as the name indicate :

OSTEO

Osteonecrosis of the jaw, commonly called ONJ occurs when the jaw bone is exposed and begins to starve from a lack of blood. The bone starts to weaken and die which usually but not always causes pain.

*The term "osteonecrosis of the jaw" was introduced by Marx in 2003 and subsequently by Ruggiero et al in 2004 as a Non-healing exposed areas of jawbone that were associated with the use of intravenous bisphosphonate therapy “BRONJ”. *In 2009, denosumab was approved by the Food and Drug Administration of the United States (FDA) and the European Medicines Agency (EMA) for the treatment and prevention of bone metastases. *In 2014, the American Association of Oral and Maxillofacial Surgeons (AAOMS) changed the term “Bisphosphonate-Related Osteonecrosis of the Jaws” (BRONJ) to “Medication-Related Osteonecrosis of the Jaws” (MRONJ)

ONJ

MRONJ (medication related)

ARONJ (antiresorptive related)

BRONJ(bisphosphonate related osteonecrosis (of the jaw

8. MEDICATION RELATED OSTEONECROSIS OF THE JAW ( MON, MRONJ)

7. ONJ can be developed spontaneously

6. Anti-angiogenic agents

5. Steroid use

4. Radiation therapy

3 Exogenous estrogens

2. Infections

such as heavy metals; for example Lead and cadmium

1. TOXIC AGENTS

What are the causes of ONJ ?

4) medical oncologists who are prescribing these drugs

3) hospital-based dentists treating oncology patients.

2) dental specialists (mostly OMF surgeons and pathologists)

1) general dentists

has been a major concern for:

particularly in those individuals on high dose parenteral antiresorptive agents

ONJ

Prolia

(Bisphosphonate or Denosumab)

( DENTAL EXTRACTION, PERIO surgery)

MINOR ORAL SURGERY

ANTIRESORPTIVE DRUGS INTAKE

RISK FACTORS For BRONJ :

2) Osteogenesis imperfecta in adults

1) Osteogenesis imperfecta in children

Non FDA approved indications include:

6) malignancies with metastasis to bone

5) Paget disease

4) Hypercalcemia of malignancy

3) Glucocorticoid induced osteoporosis

2) Osteoporosis in men

1) Treatment of osteoporosis in postmenopausal women

FDA-approved indications for bisphosphonates :include

when do we have to anticipate that the patient is taking or took bisphosphonate?

3. Diabetes

4. Smoking

2. Antiangiogenic agents intake

1. Concomitant use of steroids

Other RISK FACTORS FOR MRONJ:

Kidney cancer

Thyroid cancer

Multiple myeloma

Lymphoma

Lung cancer

Prostate cancer

Breast cancer

Virtually any type of cancer can spread to the bones, but the cancers most likely to cause bone metastasis include:

Physiologic bone remodeling

One of the underlying factors is the suppression of natural remodeling process due to the inhibition of osteoclasts.

Despite the possibly linking theories, the pathogenesis of BRONJ has not been entirely understood.

Remodeling is vital for bone healing and the suppression by bisphosphonates diminishes the healing capacity of the bone.

Pathogenesis Of BRONJ

Bisphosphonates have antiangiogenic effects.

Compromised angiogenesis would most likely be involved in post-intervention healing. "VEGF": vascular endothelial growth factor

Antiangiogenic theory of BRONJ

This molecule is a monoclonal antibody to receptor activator RANKL. RANKL binds to its receptor RANK on preosteoclasts as well as osteoclasts which is essential for the formation, function and survival of osteoclasts. Denosumab blocks the binding between RANKL and RANK thus inhibit the function, survival and formation of Osteoclast.

Mechanism Of Action Of Denosumab

Bisphosphonate differ from one another in the substitution of their active side chain.

Bisphosphonate are synthetic analogue of pyrophosphate

Classification Of Bisphosphonates

WHY?

Its is Preferentially deposited in bones with high turnover rate.

Most common sites are nonhealing dentoalveolar sites, traumatized palatal & mandibular tori and exposed portions of the mylohyoid ridge.

It results from greater reliance on osteoclast related remodeling due to occlusion and denture wearing pressure and tension forces.

And almost always began in alveolar bone due to it’s greater bone turnover rate.

BPs induced ON of jaw occurs more frequently in the mandible than maxilla.

Location

Females are more affected than males due to postmenopausal osteoporosis and breast cancer ( high incidence of metastasis to bone )

The relative risk for patients taking oral bisphosphonates for osteoporosis and the development of ONJ is unknown at this time and is estimated to be very low (1:10,000–100,000 patient years on drug therapy).

prevalence

It is clear that the benefit with respect to fracture risk reduction is far greater than the risk of ONJ in osteoporosis patients, and in oncology patients the benefit of antiresorptive therapy in lowering the risk of skeletal related events outweighed the risk of ONJ by a factor of 17

The patients most at risk of developing ONJ are those on monthly IV bisphosphonates or high-dose, subcutaneously administered denosumab (120 mg/month). The reported prevalence in the oncology patient population is between 1 and 16% of patients on high-dose therapy.

3)No history of radiation therapy to the jaws.

2)Exposed bone in the maxillofacial region that has persisted for more than 8 weeks

1)Current or previous treatment with a bisphosphonate

Patients may be considered to have MRONJ if they have all of the following criteria:

The American Society for Bone and Mineral Research define MRONJ as follows

Pain, teeth mobility, mucosal swelling, erythema and ulcerationIntra or Extra oral Fistula Altered sensation in the affected area

Signs and Symptoms

Stage 3: exposed bone with infection and extension radiographically to the inferior border of the mandible or sinus floor in the maxilla or presence of an extra oral fistula or pathologic fracture

Stage 2: exposed bone with evidence of infection with or without purulent discharge

Stage 1: exposed bone with no infection and otherwise asymptomatic

Three stages of ONJ have been proposed and this classification is currently in use.

Imaging is of value in diagnosing ONJ. This is particularly the case in individuals on antiresorptive therapy with ONJ-like symptoms but without obvious bone exposure. As periapical and periodontal disease is an important risk factor for ONJ. identifying early dental disease with imaging and proceeding with dental preventive measures may decrease the risk of ONJ and minimize the need for dental extractions.

Role of Imaging in Diagnosis

Increased trabecular density

It has been proposed that serum C-terminal telopeptide of type-1 collagen (CTX), a break down product of type-1 collagen during bone resorption, can be followed in the patient's serum as a risk indicator for development of ONJ.

What is CTX Blood Test ?

Patient with full or partial dentures should be examined for areas of mucosal trauma

Optimal periodontal health should be achieved

Non restorable teeth and those with poor prognosis should be extracted.

3) Avoiding future extractions

2) Optimizing dental and oral health

1) Patient education

IF IT POSSIBLE THE INITATION OF IV BP THERAPY SHOULD BE DELAYED UNTIL THE DENTAL HEALTH IS OPTIMISED

PREVENTION:

4) providing primary closure over bony wounds wherever possible

3) minimizing sharp bony edges

2) Careful surgical technique

1) prophylactic antibiotic both topical and systemic

If minor surgery is needed should include;

First of all any surgical therapy should be minimized, especially if there is alternative such as endodontic therapy.

Dental Management

It is the simplest and fastest type of wound closure

PRIMARY INTENTION WOUND HEALING :

  • Lower the risk of infection
  • Minimal tissue loss
  • Minimal Scarring

They are at much reduced risk, but there is reported cases and the duration is very important since most reported cases occur after 3 years of exposure.While if there is concomitant steroid use less than 3 years would be enough.

drug holiday FOR THESE PATIENTS DISCONTINUATION OF BP THERAPY BEFORE 3 MONTHS OF SURGERY MAY REDUCE THE RISK

Patients on oral BP

Non restorable teeth that require extraction may be treated by the removal of the crown and endo treatment for the remaining roots.

Procedures that involve direct osseous injury should be avoided.

1-16% of them are at risk.

. Discontinuing the IV medication Provide no short term benefit since the effect of the drug may remain for extended period of time.

Patients On Iv BP

Other routine restorative, hygiene, orthodontic and endodontic dentistry can be conducted as usual.

Surgery should be avoided if possible ( since it is difficult to obtain a surgical margin with viable bleeding because the entire jawbone is under the effect of BP ) Areas of necrotic bone that are source for soft tissue irritation should be removed or recontoured without exposing adjacent bone. Loose segments of bony sequestrum should be removed without exposing the uninvolved bone.

Patient diagnosed to have BRONJ General Principles In Management

Stage 1

Stage Specific Treatment

Oral antimicrobial rinses. No surgical treatment is indicated unless the area of exposed bone are irritating surrounding soft tissues. The patient should be examined every 3 month.

Stage 1

Stage 2

Stage 1

Stage Specific Treatment

Oral antimicrobial rinses. AB ( mostly is sensitive to pencilline, metronidazole, clindamycine and erythromycin). In refractory patient the might need IV antibiotics.

Stage 2

Stage 3

Stage 2

Stage 1

Stage Specific Treatment

The most challenging, usually these cases are refractory to antibiotics At this stage the surgical intervention is indicated + IV antibiotics

Stage 3

two months after dental extraction

painful exposed bone

intravenous zoledronic acid monthly for three years

relapse of the breast cancer with bony metastasis

radiation

chemotherapy

modified radical mastec-tomy

breast cancer

A 42-year-old woman

Case Report

The dentist found yellow-white discoloration of exposed bone, surrounding a soft tissue inflammation.

A radiological study showed bone destruction of the left body of the mandible

therefore, curettage, conservative otoplasty and saline irri- gation was done

Initially, conservative removal of exposed bone with primary closure was performed and systemic antibiotic given Notwithstanding, she developed a non-healing socket surrounded by mucosal inflammation

of her underlying disease in February 2007.

died

lost to follow up

finally she was

at the last visit she still had non-healed socket with mild soft tissue inflammation

underwent saline irrigation multiple times with minimal recovering of affected area

The patient followed up with the dentist

The best way to manage this serious complication is to prevent it from happening

JUST AS ANY DISEAS IN THE WORLD

THANK YOU

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