Transcript Medication-related osteonecrosis of the jaw (MRONJ) – Risk Factors

Medication related osteonecrosis of the Jaw
PHUU PWINT HAN
ASSISTANT PROFESSOR OF CLINICAL DENTISTRY
PIEDAD SUAREZ DURALL
ASSOCIATE PROFESSOR OF CLINICAL DENTISTRY
OSTROW SCHOOL OF DENTISTRY OF USC
PAETC
Objectives
• Recognized the comorbidities associated to HIV, that can cause low
bone density.
• Understand and recognize the risk factors to develop medication
related osteonecrosis of the jaw (MRONJ).
• Compare the different stages of medication related osteonecrosis of
the jaw.
• Able to interpret the recommendations from the AAOMS to prevent
and manage medication related osteonecrosis of the jaw.​
Classic
Fam Hx
age
Alcohol
Physical Act
Female
2nd
Chronic Disease
HIV
Direct effect on
bone cells
Immune
Activation
Bone
Mineral
Density
Vit D
Hypogonadism
Renal Dysfunction
Malnutrition
Body mass
MEDS
ART
http://www.clinicaloptions.com/HIV/Annual%20Updates/2012
Curr Opin Rheumatol. 2012 Sep;24(5):567-75.
HIV and its effects on bone: a primer for rheumatologists.
Gedmintas L, Solomon DH.
Abstract
PURPOSE OF REVIEW:
As patients with HIV are living longer because of effective treatments, rates of comorbid
chronic diseases such as bone complications are increasing.There is a growing body of literature showing increased rates of
osteopenia and osteporosis in the HIV population. Less is known about the risk of fracture, as well as other bone
complications, such as avascular necrosis (AVN).
RECENT FINDINGS:
Increased rates of osteopenia and osteoporosis are seen in the HIV population, likely secondary to an interaction of traditional
osteoporotic and HIV-specific risk factors, and possibly the effect of antiretroviral therapy (ART).There are conflicting recent
data as to whether the decrease in bone mineral density seen in the HIV population, specifically with particular ART regimens,
translates into an increased risk of fracture. Conflicting evidence emerges from recent studies exploring whether
supplementation of vitamin D and calcium can prevent the bone loss seen with specificART regimens.
SUMMARY:
Bone disease is common in the HIV population, and will likely be a medical problem increasingly seen by rheumatologists.The
role of ART regimens on bone complications such as fracture and AVN is unclear, and further research in this area as well as
possible prevention strategies are needed.
Bone Disease
The presence of osteopenia has been estimated to be
6 fold higher and that osteoporosis nearly 4 fold higher in
HIV infected individuals
• Evidence that cART exacerbates bone disease includes
bone mineral density reduction after initiation of
therapy.
• A meta-analysis found the odds of osteoporosis to be 4
fold higher in patients receiving cART than in treatmentnaïve individuals.

Hui Zhao and Matthew Bidwell Goetz. Journal of Antimicrobial Chemotherapy Complications of HIV infections in ageing population: challenges in
managing older patients on long-term combination antiretroviral therapy. March, 2011
Medication related osteonecrosis of the Jaw
2014 Update
Position Paper American Association of Oral
and Maxillofacial Surgeons
http://www.aaoms.org
Medication-related osteonecrosis of the jaw
(MRONJ)
Medication-Related Osteonecrosis of the Jaw – 2014 Update
AAOMS Positioning Paper Pg. 18 – 19.
Bisphosphonates
Bisphosphonates
• Can be given orally or parentally
• Prevention and treatment of osteoporosis and osteopenia
• Oral Bisphosphonates
• IV Bisphosphonates - once yearly infusion of zolendronate (Reclast®) and a
parenteral formulation of ibandronate (Boniva®) administered every three
months
• Managing cancer-related conditions including:
• hypercalcemia of malignancy, skeletal-related events (SRE) associated with bone
metastases in the context of solid tumors such as breast cancer
• prostate and lung cancers
• Managing of lytic lesions in the setting of multiple myeloma
• IV bisphosphonates
Bisphosphonate related osteonecrosis of the
jaw
• First reported by Max and Stern in 2002
• Exposed, non-healing bone in patients receiving pamidronate (Aredia,
Novartis) for bone metastasis; when debridement was performed, the
condition worsened to increased amounts of exposed bone
• First publication by Max in 2003 in the Journal of Oral and
Maxillofacial Surgery (JOMS) with 36 cases associated with IV
bisphosphonates (pamidronate or zoledronate)
• Phossy jaw – Similar condition reported in literature in Phosphate
miners more than 100 years earlier
Bisphosphonate related Osteonecrosis of
the Jaw
• Current or previous treatment with bisphosphonate therapy
• Exposed bone in maxillofacial region for more than 8 weeks
• No history of radiation treatment to the jaws
Why jaw bone?
• Under constant remodeling
• Non-sterile environment
• Prone to trauma and bone exposure
Medication-related osteonecrosis of the jaw (MRONJ)
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementA
dvisoryCommittee/UCM270958.pdf (last accessed 7/2/2014) page 19.
AAOMS Recommendations
Photos and X-rays courtesy of Dr. Mulligan and Dr. S. Kumar
Ann Intern Med. 2006;144(10):753-761.
Management
• Before starting drug therapy
• Oral health assessment
• Necessary dental work before starting bisphosphonate therapy
• Patients who are on bisphosphonate therapy
• Oral or IV
• For what reason
• Duration
• Risk of Medication-related osteonecrosis of the jaw (MRONJ) – Local and
systemic factors
Medication-related osteonecrosis of the jaw
(MRONJ) – Risk Factors
1. Medication related risk factors
•
•
•
The risk of ONJ among cancer patients exposed to zolendronate and denosumab
ranges between 50-100 times higher than cancer patients treated with placebo.
Cumulative incidence 0.7 – 6.7% (~1%)
Stay in the bone for many years ~10 years
2. Osteoporosis Patients
•
Oral BPs: 0.1% (10 cases per 10,000) which increased to 0.21 (21 cases per 10,000)
among patients with greater than 4 years of oral BP exposure
3. Duration of Medication Therapy
•
•
IV therapy – risk increased each year for the first 3 years
Oral BPs – 0.21% after 4 years or more (median duration 4.4 years, minimum 2.6 years)
4. Others
•
•
Soft tissue toxicity by BP
Innate or acquired immune dysfunction
Medication-related osteonecrosis of the jaw
(MRONJ) – Risk Factors
5.1 million patients over the age of 55
years received a prescription
for a bisphosphonate in year 2008.
Every 100 U.S. population, seven
patients received a prescription for a
bisphosphonate in the outpatient
setting.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskM
anagementAdvisoryCommittee/UCM270958.pdf (last accessed 7/2/2014) page 19.
Medication-related osteonecrosis of the jaw
(MRONJ) – Risk Factors
1.
2.
3.
4.
5.
Operative Treatment
•
•
•
•
Dentoalveolar Surgery (extraction, implant placement, periodontal surgery)
Tooth extraction - 52 to 61%, 16 - 33 folds increased risk (cancer patient on IV BP)
No data for the risk for ONJ for other procedures.
AAOMS: dental implant placement and endodontic or periodontal procedures that require exposure and
manipulation of bone are comparable to the risk associated with tooth extraction
Anatomic factors
•
•
Mandible (73%), Maxilla (22.5%), Both (4.5%)
Dentures
Concomitant oral disease
•
•
Periodontal disease, Periapical pathology
Associated with tooth extraction
Demographic, Systemic factors and other Medication factors
•
•
•
•
Age, Sex
Anemia (hemoglobin < 10g/dL ), Diabetes
Corticosteroids, Anti-angiogenic drugs
Smoking
Genetic factor
AAOMS Recommendations
Patients about to initiate intravenous antiresorptive or antiangiogenic
treatment for cancer therapy
• Patient education
• Non-restorable teeth and those with a poor prognosis should be extracted.
• Complete the necessary elective dentoalveolar surgery
• Delay the antiresorptive or antiangiogenic therapy if systemic conditions
permit, until the extraction site has mucosalized (14-21 days) or until there
is adequate osseous healing
• Dental prophylaxis, caries control and conservative restorative dentistry are
critical to maintaining functionally sound teeth
• Examine full or partial dentures for areas of mucosal trauma, especially
along the lingual flange region
AAOMS Recommendations
Patients receiving intravenous antiresorptive or antiangiogenic
treatment for cancer therapy
• Oncology Patients Receiving Monthly Antiresorptive Therapy : Tooth
extraction should be avoided if possible
• If ONJ develops the oncologist may consider discontinuing
antiresorptive therapy until soft tissue closure has occurred,
depending on disease status.
AAOMS Recommendations
Patients about to initiate antiresorptive treatment for osteoporosis
• Educate patient - very small risk (<1%) of compromised bone healing
• Depending on the duration of therapy and other risk factors
• Use of systemic markers of bone turnover as a measure of MRONJ risk is
not recommended
• Osteoporosis/Osteopenia: No evidence that interrupting bisphosphonate
therapy alters the risk of ONJ in patients following tooth extraction
• Patients with extended exposure histories (>4 yrs): Consider drug holiday
for at least two months prior to oral surgery until osseous healing occur
with the prescribing physician if systemic condition permit (Theoretical
recommendation - No evidence)
Other Recommendations
• Biopsy only if metastasis is suspected.
• Forego elective surgery including Implants
• Routine Dentistry: restorations, local and atraumatic periodontal therapy with RCT to avoid
extractions
• Consider placement of protective stent to protect exposed bone, or when such bone causes
trauma to adjacent tissue or is further insulted with normal function.
• Management issues relative to removable prostheses: must be hygienic, cleaned daily and
removed at night, well-fitting with no risk of soft tissue trauma.
• Amoxicillin 500mg tid 14 days or Clindamycin 300mg tid for 15 days or Azithromycin 250mg
qd for 10 days
• Other anti-microbial therapy: Intermittent or continuous based on findings of cultures:
quinolones, doxycycline, erythromycin.
• Refractory cases may require combination AB therapy; long-term AB maintenance; or
intravenous AB therapy. Anti-fungal medications may be needed.
• Recall Schedule: monitor every 3 months unless additional problems develop.
• Hyperbaric Oxygen: not shown to be effective.
Protocol for Prevention of BONJ at USC
Patient at risk before oral surgery/extraction
• Patient education and Consent form
• 0.12% Chlorhexidine Gluconate Rinse (3 times/day) 1 week pre-op to
until complete healing
• Systemic antibiotic 3 days pre-op and 4 days post-op (Amoxicillin
500mg tid or Clindamycin 300mg bid)
• Nystatin rinse (3 times/day) 1 week pre-op in high risk patient
• Immediate pre-op Chlorhexidine rinse
• Weekly or biweekly follow up until complete healing to assess and
manage the wound
Protocol for Active BONJ at USC
Patient with active localized BONJ
• Early: 0.12% Chlorhexidine Gluconate Rinse and
• 1:100,000 units Nystatin (3 times/day) until complete healing,
systemic antibiotic if necessary
• Advanced: Surgical therapy and/or systemic antibiotic
• Oral medicine consult
• Regular follow up
80 Y old male patient with stage IV prostate cancer with colon metastasis
IV Zometa once a month for 2 year when he came in
09/10/2008
02/13/2009
04/21/2010
03/14/2012
75 YO Asian female patient, Fosamax once a
week for 1 and half years
Dr.Phuu Han
Dr T. Wada
Dr T. Wada
Thank You!