MRONJ Flashcards
what are bisphosphonates
are anti resorptive medications that inhibit osteoclast activity and bone resorption, used to treat osteoporosis and cancer related conditions
what are some non malignant bone diseases treated using bisphosphonates
- metabolic bone disorders
- pagets disease
- osteogenesis imperfecta
- rheumatoid arthritis
names of Oral bisphosphonates
alendronate, risedronate
names of IV bisphosphonates
Ibandronate, Zolendronic acid
half life of bisphosphonates
10 years, binds strongly to HAP
How does Denosumab work
Is a monoclonal antibody that inhibits osteoclast function and bone resorption by acting as a RANK ligand inhibitor, used in treatment for osteoporosis and cancer treatments. It is administered subcutaneously every 6 months, does not bind to bone and its effects diminish within 6-9 months
3 criteria for diagnosing MRONJ
1) current or previous treatment with anti resorption therapy
2) exposed bone or bone that can be probed through an intra oral / extra oral fistula for more than 8 weeks
3) no history of radiation therapy or metastatic disease to the jaws
Pathophysio of anti resorptive drugs causing MRONJ
1) inhibition of bone remodelling (central hypothesis). Normally in response to mechanical stress, alveolar bone exhibits higher turnover rate but AR drugs inhibit osteoclast formation, differentiation and function, causing decreased bone resorption and remodelling and hence delayed healing
2) infection and inflammation, presence of dental conditions like perio will create an inflammatory environment that may exacerbate effects of anti resorption medications
3) inhibition of angiogenesis - some BP directly inhibit angiogenesis -> decrease in vascularity at MRONJ sites, hence chronic ischemia leading to avascular necrosis
4) innate or acquired immune dysfunction- immunocompromised patients are at higher risk for MRONJ
MRONJ incidence in cancer and osteoporosis patients
cancer <5%
osteoporosis <0.05%, BP 0.02%-0.05% and Denosumab 0.04-0.3%
Risk factors for MRONJ
1) treatment indication (cancer higher risk than osteoporosis)
2) duration of use (more than 2 years got higher risk)
3) concurrent medication (if got long term glucocorticoid use or chemotherapy then higher risk)
4) type of antiresorptive used (Denosumab or IV BP higher risk)
5) location (posterior mandible higher risk)
6) concomitant oral disease (pre existing disease like perio disease got higher risk)
7) innate or acquired immune dysfunction (diabetes, RA, Immunocompromised)
staging for MRONJ
STAGE 0
Symptom
- non specific pain associated with teeth, mandible,maxilla or sinus
- neurosensory dysfunction
clinical
- no exposed bone
- loose teeth excluding perio disease
- i/o or e/o swelling
radiographic
- non specific alveolar bone loss
- osteosclerosis
- thickening of LD
STAGE 1
Asymptomatic
Clinical
- exposed bone or probable though a fistula
- no inflammation or infection
radiographic
- localised bone changes to the alveolus (bone loss, osteosclerosis)
STAGE 2
Symptomatic
Clinical
- exposed bone or probable through fistula
- inflammation or infection
Radiographic
- localised bone changes to the alveolus (bone loss, osteosclerosis)
STAGE 3
Symptomatic
Clinical
- exposed bone or probable through fistula, beyond alveolar bone
- evidence of infextion
- e/o fistule, oro antral/oro nasal communication, osteolysis to inferior mandibular border or sinus floor
radiographic
- localised bone changes beyond alveolus to inferior mandibular border/ sinus floor, pathological fracture
MANAGEMENT OF MRONJ
first is PREVENTION
1) medical
- smoking cessation
- diabetes control
- drug holiday (but evidence is inconclusive)
2) dental
- perform high risk procedures like extractions prior to initiating therapy (denal clearance)
- regular reviews
- peri operative antibiotics
- anti microbial mouth rinse
- primary closure of exo sites
- minimise trauma from prostheses
then onto legit TREATMENT which objective is curative therapy (mucosal closure), split into 3 categories
1) conservative mx
- local wound care
- antimicrobial rinses
- removal of loose sequestrum
- systemic antibiotics
- pain control and control of secondary infection
- limited evidence for HBO
- then based on different stages of disease, got different management
2) surgical intervention
- remove sequestrum and soft tissue closure
- marginal/ segmental resection with or without flap
- rsections should be done with margins beyond bleeding bone
- based on different stages of disease also got different management
3) others
- pentoxifylline, is used to treat peripheral artery disease and fibrosis. causes vasodilation and increases peripheral blood flow
- tocopherol (vit E). has antioxidant effect, reduces inflammation and protects cell membranes from free radical damage generated during oxidative stress
which stage of MRONJ need systemic antibiotics
stage 2 and 3 need systemic antibiotics, stage 1 dont need.
all 3 stages also give antimicrobial rinse and pain control!
notes on pentoxifylline
- moa
- dosage
- aims to create ideal bone microenvironment for healing
- preceded by anti inflammatory, antifungal and antibiotic treatment to control local superinfection (4-6 weeks)
- protocol of PTX (600mg BD) and tocopherol (800 IU once) for 2 months pre surgery
- when we see clear separation between necrotic and vital bone assessed with CBCTMRI, then the protocol must be continued for 6 months post surgery
