Medicine related osteo necrosis of the jaw – What is the best clinical practice?V Murugaraj BDS, MFDS RCS (Eng), FFD RCSI Oral surgery Oral medicine (Ire)

Abstract

Medicine related osteonecrosis of the jaw commonly referred by the acronym MRONJ is an uncommon but potentially a serious side effect on patients related to Antiresorptive therapy, which results in exposed avascular necrotic bone involving either maxilla or mandible. This condition poses a serious challenge to the Dental and maxillofacial specialty due to the complex pathogenicity, propensity to affect the maxillofacial skeleton more frequently than other bones in the body and the best way to manage remains sub optimal. Although bisphosphonates remains the most commonly used drug there are other agents available as an alternative. This article aimed to identify the risks, prevention and management of this condition in the primary dental care.

Introduction

Anti resorptive drug use has been increasing in recent years. This is a group of medications that inhibits osteoclast induced bone resorption therefore stabilize bone loss and prevent low impact fractures in benign conditions such as osteoporosis, osteopenia and Paget’s disease. They also play an important role in patients with metastatic cancer including breast, lung, prostrate and multiple myeloma by preventing cancer spread to the bone and to treat resorption defects, thereby improving quality of life in these patients.

Risk factors

MRONJ is most commonly associated with procedures that stimulate the bone and therefore particularly associated with exodontia, periapical and periodontal surgery. Some non-interventional cause for example cysts can also lead to this condition.About 2/3 of reported cases so far associated with mandibular molar extractions, trauma related to dentures is the second most common cause following dento alveolar surgery. lingual bone exposure adjacent to mandibular molar either spontaneous or following surgery are also common

. General

Immunosuppression- Diabetes, Rh arthritis, HIV

Patients on steroids and other Immunosuppressive drugs

Smoking

Poor oral hygiene- periodontal disease

Therapeutic head and neck radiation

Local Mandibular molar extractions

All dento alveolar surgery

Trauma related to dentures

Thin mucosal covering -lingual mucosa

High h

High risk patients

Patients on Oral Bisphosphonates for more than 3 years

Patients on Intravenous Bisphosphonates for more than 12 months

Prevention1. Physician

Physician should refer the patient to the General dental practitioner for dental assessment prior to starting Anti resorptive therapy with clear written referral indicating type of drug. duration of therapy and the reason for prescribing..

Risks and benefits of drug therapy including osteonecrosis of the jaw must be discussed with the patient

2. Dentist The aim of assessment is to identify the risk, eliminate infection and preventing the need for invasive procedure in the future. Partially erupted teeth, teeth with poor prognosis in the long term should be extracted. Impacted, unerupted teeth covered by bone or soft tissue completely should be left undisturbed Review existing dental prosthesis and any sharp clasp or rough margins should be rectified. Bone pathology eg. cyst must be treated appropriately with further referral to secondary care if required.

Timing of treatment Any extraction if required need to be done at least one month prior to therapy. If patient requires urgent Anti resorptive drug treatment, the most invasive procedure should be carried out first followed by less invasive and non-invasive treatment as the risk of MRONJ is related to long term use .In other words the risk increases with time

General

Immunosuppression- Diabetes, Rh arthritis, HIV

Patients on steroids and other Immunosuppressive drugs

Smoking

Poor oral hygiene- periodontal disease

Therapeutic head and neck radiation

Patient requiring Dental treatment during drug therapyAvoid high risk procedure as much as possible

Restorative and Noninvasive periodontal treatment should be considered

Tooth or teeth which cannot be restored should be decoronated followed by root canal treatment of remaining roots

Tooth with Grade 1&2 mobility must be appropriately splinted however tooth with grade 3 mobility should be extracted with appropriate precaution as there is a strong chance of necrotic bone already present in the jaw.

Surgical techniqueAtraumatic/Minimal trauma to soft tissue and bone whenever possible.

Local anesthetic without vasoconstrictors must be used to minimize compromised blood supply.

If the procedure requires flap elevation then minimal flap retraction avoiding too much trauma to soft tissue and periosteum followed by minimal bone removal with good irrigation to avoid excessive thermal injury to the bone should be performed. Whenever possible tooth division rather than bone removal should be considered.

Extraction socket must be closed with loose sutures with good seal after smoothening any sharp edges ensuring no exposed bone as much as possible

Drug holidayThis is an effort to reduce the risk of MRONJ and is mainly indicated for high risk patients. It involves discontinuation of drug 3-6 months prior to any invasive procedure and restart the drug once complete healing has taken place.controversie still exist as whether such an attempt could be successful or not considering half life of the drug mainly bisphosphonates..

Also stopping the drug for a period of 3-6 months may not be an issue with benign conditions however such attempt may not be advisable on patients with metastatic cancer as the risk outweighs the benefits.

Antibiotic prophylaxis and RationaleProphylactic antibiotics should be considered on high risk patients based on the fact that both soft tissue and bone healing are already impaired by the Antiresorptive drugs and further interference to this in the form of wound infection can worsen the situation.

Therefore an antibiotic with broad spectrum of activity is recommended which are based on Spanish and Australian guidelines further supported by some small studies in UK

Antibiotic prophylaxis

Amoxicillin 3g 1 hour pre op, 500mg tds 1 week post op

or

Clindamycin 300mg I hour pre op, 150mg qds 1week post op

Chlorhexidine 0.2% 1 week pre op + 21 days post op

Management in Primary care

Asymptomatic Exposed bone – Conservative management with regular follow-up

Exposed bone with pain – combination of analgesics

Exposed bone with pain and infection- penicillin v +chlorhexidine m/w

As the necrotic bone is structurally sound to support the jaw function any exposed bone with no

associated symptoms are treated conservatively with regular follow-up

Exposed bone with associated pain and no sign of infection are treated with strong analgesics

Exposed bone with pain and infection are best treated in Hospital setting as the main goal of treatment

is to prevent development of osteomyelitis

Anti resorptive agents in use other than Bisphosphonates

Denosumab Monoclonal antibody Inhibit osteoclastic activity- RANKL(receptor activator of nuclear factor kappa b ligand

Amoxicillin 3g 1 hour pre op, 500mg tds 1 week post op

or

Clindamycin 300mg I hour pre op, 150mg qds 1week post op

Chlorhexidine 0.2% 1 week pre op + 21 days post op

Infusimab Monoclonal antibody Inhibit osteoclastic activity- RANKL(receptor activator of nuclear factor kappa b ligand)

Bevacizumab tyrosine kinase inhibitor Inhibit ( VEGF)vascular endothelial growth factor

Sunitinib tyrosine kinase inhibitor Inhibit ( VEGF)vascular endothelial growth factor

Carbozantanib tyrosine kinase inhibitor Inhibit ( VEGF)vascular endothelial growth factor

Odanacatib selective cathepsin K inhibitor Inhibit osteoclast function but preserves osteoclast viability

Radium-223

Strontium -89 Form of internal radiotherapy.