This document discusses medicine-related osteonecrosis of the jaw (MRONJ), a serious side effect of antiresorptive therapy involving exposed necrotic bone in the jaw. It notes that MRONJ risk is associated with dental procedures and is most common in the mandible. It provides guidelines for prevention, including dental evaluation prior to starting therapy, conservative treatment of at-risk teeth, and use of antibiotic prophylaxis for high-risk patients undergoing invasive procedures. For management of exposed bone, it recommends a conservative approach for asymptomatic cases and use of analgesics and antibiotics for symptomatic cases or those with infection.

1. Medicine related osteo necrosis of the jaw – What is
the best clinical practice?
V Murugaraj BDS, MFDS RCS (Eng), FFDRCSI Oral surgeryOral medicine (Ire)
Abstract
Medicine related osteonecrosis ofthe jaw commonly referred by the acronym MRONJ is an uncommon but
potentially a serious side effecton 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 affectthe
maxillofacial skeleton more frequently than other bones in the body and the bestway to manage remains
sub optimal. Although bisphosphonates remains the mostcommonly used drug there are other agents
available as an alternative. This article aimed to identify the risks, prevention and managementofthis
condition in the primary dental care.
Introduction
Anti resorptive drug use has been increasing in recentyears. This is a group of medications that inhibits
osteoclastinduced bone resorption therefore stabilize bone loss and preventlow impactfractures 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 oflife in these patients.
Risk factors
MRONJ is most commonly associated with procedures thatstimulate 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.
About2/3 ofreported cases so far associated with mandibular molar extractions, trauma related to
dentures is the second mostcommon cause following dento alveolar surgery. lingual bone exposure
adjacentto mandibular molar either spontaneous or following surgery are also common
Local
Mandibular molar extractions
All dento alveolar surgery
Trauma related to dentures
Thin mucosal covering -lingual mucosa

2. .
Highh
High risk patients
Patients on Oral Bisphosphonates for more than 3 years
Patients on Intravenous Bisphosphonates for more than 12 months
Prevention
1. Physician
Physician should refer the patient to the General dental practitioner for dental assessmentprior to
starting Anti resorptive therapy with clear written referral indicating type of drug. duration of
therapy and the reason for prescribing..
Risks and benefits ofdrug therapy including osteonecrosis ofthe jaw must be discussed with the
patient
2. Dentist
The aim of assessmentis 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 softtissue completely should be leftundisturbed
Review existing dental prosthesis and any sharp clasp or rough margins should be rectified.
Bone pathology eg. cystmust be treated appropriately with further referral to secondary care if
required.
Timing of treatment
Any extraction if required need to be done atleastone month prior to therapy.
If patient requires urgentAnti resorptive drug treatment, the mostinvasive procedure should be
carried outfirst followed by less invasive and non-invasive treatment as the risk ofMRONJ is
related to long term use .In other words the risk increases with time
General
Immunosuppression-Diabetes,Rharthritis, HIV
Patients on steroidsandother Immunosuppressive drugs
Smoking
Poor oralhygiene- periodontaldisease
Therapeuticheadandneckradiation
Chemotherapeutic agents

3. Patient requiring Dental treatment during drug therapy
Avoid high risk procedure as much as possible
Restorative and Noninvasive periodontal treatmentshould be considered
Tooth or teeth which cannot be restored should be decoronated followed by rootcanal 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 presentin
the jaw.
Surgical technique
Atraumatic/Minimal trauma to soft tissue and bone whenever possible.
Local anesthetic without vasoconstrictors mustbe 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 socketmustbe closed with loose sutures with good seal after smoothening any sharp edges
ensuring no exposed bone as much as possible
Drug holiday
This is an effort to reduce the risk ofMRONJ and is mainly indicated for high risk patients. It involves
discontinuation of drug 3-6 months prior to any invasive procedure and restartthe drug once complete
healing has taken place.controversie still existas whether such an attempt could be successful or not
considering halflife of the drug mainly bisphosphonates..
Also stopping the drug for a period of3-6 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 Rationale
Prophylactic antibiotics should be considered on high risk patients based on the factthat 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

4. Antibiotic prophylaxis
Management in Primary care
Asymptomatic Exposed bone – Conservative managementwith regular follow-up
Exposed bone with pain – combination ofanalgesics
Exposed bone with pain and infection- penicillin v +chlorhexidine m/w
As the necrotic bone is structurally sound to supportthe jaw function any exposed bone with no
associated symptoms are treated conservatively with regular follow-up
Exposed bone with associated pain and no sign ofinfection are treated with strong analgesics
Exposed bone with pain and infection are best treated in Hospital setting as the main goal oftreatment
is to preventdevelopmentofosteomyelitis
Amoxicillin 3g 1 hour pre op, 500mg tds 1 week postop
or
Clindamycin 300mg I hour pre op, 150mg qds 1week postop
Chlorhexidine 0.2% 1 week pre op + 21 days postop
+/_ Blow down splint

5. Anti resorptive agents in use other than Bisphosphonates
Denosumab Monoclonal antibody
Inhibit osteoclastic activity- RANKL(receptor activator of nuclear factor kappa b ligand
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 osteoclastfunction but preserves osteoclastviability
Radium-223
Strontium -89 Form of internal radiotherapy.