MRONJ & ORN 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 than oral BP)
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)
8) demographic: females got increased prevalence due to agents prescribed for underlying disease eg breast cancer or osteoporosis
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
how should drug holiday for DMB be done
- is controversial
- used to be recommended but now cant really reach consensus
- believed that the risks of potential deleterious effects of suspending AR therapy outweighs the benefit
- because discontinuation will cause rebound increase in bone resorption and hence increase risk of fracture
- must optimise timing and duration of holiday to minimise risk
- perform sugery 3-4 months after the last done (when osteoclast inhibition waning)
- only reinstitute 6-8 weeks post surgery
defn of osteoradionecrosis
is the presence of exposed or necrotic bone for more than 3 months following radiation therapy
aetiology of ORN
high doses of radiation will kill osteoblasts and stimulate osteoclastic bone resorption. radiation also damages endothelial cells in smaller vessels leading to hypocellular and hypovascular bone
risk remains throughout the patients lifetime
radiation also damages the mucosal covering which exposes the necrotic bone to the oral environment
infections, dental exo and denture trauma can exacerbate ORN
HOW is ORN staged
classified based on its response to hyperbaric o2 therapy (Marx 1983)
stage 1: exposed alverolar bone without pathologic fracture, which responds to HBO therapy
stage 2: refers to disease that doesnt respond to HBO therapy and requires sequestrectomy and saucerisation
stage 3: full thickness bone dmaage or pathological fracture, requires complete resection and reconstruction with free tissue
radiographic presentation of ORN
- if ORN is suspected, CT imaging is the modality of choice
- radiographic features of ORN are similar to OM - ragged, patchy, moth eaten radiolucent areas of bone destruction and the presence of radiopaque sequestra
but no periosteal bone reaction in ORN because of death of osteoblasts
pathologic fractures may also be seen
mx of ORN
current mx of ORN is unsatisfactory because of poor wound healing.
includes decortication with sequestrectomy and hyperbaric o2 with antibiotics
for elective dental procedures, can:
- minimise hypovascularity using non lidocaine LA
- avoid use of vasoconstrictor
- minimise trauma
possible radiographic features after H&N radiotherapy
- irregular but uniform widening of PDL space (different from perio and endo pdl space widening) - 88%
- bony sclerosis 32%
- periodontal disease like bone loss
- bone resorption
what precautions to be taken for extractions after radiotherapy
1) routine extraction should be done with primary soft tissue closure
2) peri operative systemic antibiotics (for all exos? or only surgical?)
3) HBO before and after exo
- increases local tissue oxygenation + vascular ingrowth into hypoxic tissues
- 20 to 30 HBO dives before, 10 more dives after exo
- Marx found significant decrease in ORN
4) PERI operative PENTO (pentoxifylline + tocopherol)
5) antiseptic mouth rinse - CHX or povidone iodine
what to do to prep dentition for radiotherapy, and what is the maintenance after irradiation
1) extract all questionable/ poor prognosis teeth
- usually surgical exo to remove sharp bone, achieve primary mucosal closure
- prophylactic ab during exo
- during the surgical exo, can do bone recontouring also because remodeling capacity of the body is greatly reduced after radiation therapy
- RT should wait 1-2 weeks after exo, when soft tissues have healed sufficiently
2) remove PE 3M to prevent pricoronal infection
- can keep if it is totally in bone
3) thorough prophy + topical fluoride
4) OHE OHI
5) round off sharp cusps of teeth to prevent mechanical irritation
6) advise to stop smoking & alcohol as these can irritate mucosa
7) soft denture liners for denture patients
8) ideally can consider implant supported dentures to avoid contact between denture and mucosa because the patient is prone to oral mucositis due to thin and less keratinised epithelium and reduced vasculature, hence ulceratiions
DURING RADIO
- rinse mouth at least 10x/day with saline rinses
- CHX mouth rinse 2x a day to prevent bacteria/ fungal infections
AFTER RADIO
- regular mainetnance every 3-4 months ( we want to identify caries quickly to repair with CR/AR)
- prophy + topical fluoride
- recommend fluoride mouthrinse
- monitor for onset of trismus
what are the shared predisposing factors across OM, MRONJ and ORN?
1) SYSTEMIC factors
- malnutrition
- DM
- leukemia
- alcoholism
2) DECREASED VASCULARITY
- osteopetrosis
- sickle cell anemia
3) IMMUNOSUPPRESSION
- aids
4) steroids or chemotherapy
