Bisphosphonates and dental
management Dr Alison Boulter
An emerging complication of pharmacological intervention
BRONJ Definition
Exposed Bone
Maxillofacial region
>8 weeks duration
Bisphosphonate exposure
No history of radiation therapy to craniofacial region
AIMS
Summarise Bisphosphonates
Incidence rates BRONJ
Discuss pathogenesis and risk factors
Clinical and radiographic features
Management
Prevention and dental treatment
Bisphosphonates
Used for:
Skeletal complications breast ,renal & prostate cancer - bone
metastates, hypercalcaemia
Multiple Myeloma
Paget's Disease
Osteoporosis
Osteogenesis imperfecta
Bisphosphonates - basic structure
Bisphosphonates - Pharmacology
Bisphosphonates - why they work
Bisphosphonates are potent inhibitors of osteoclast function
Inhibit human endothelial cell proliferation, adhesion and migration
Bisphosphonates - Pharmacology
Intravenous
Pamidronate (Aredia)
Clodronate
Ibandronate (Bondromat)
Zolendronic Acid (Zometa)
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Oral
Etidronate (Didronel)
Aledronate (Fosamax, Fosamax plus D)
Risedronate (Actonel)
Ibandronate (Boniva)
Clodronate (Bonefos, Loron)
Tiludronate (Skelid)
BRONJ Incidence - 2008 studies
BRONJ Incidence
Higher numbers reported by:
Council on Scientific Affairs of the ADA
170 cases secondary to alendronate
Medical claims data bases
In contrast:
No reported BRONJ in osteoporosis or Paget's treated BP's : RCT's
or well - designed clinical trials testing efficacy and safety
Black 2007, Pazianas 2007, Gueiros 2008, Reid 2008, Edwards 2008
BRONJ Incidence - variation in literature
>900 citations in Pub med
Case Studies
Reviews
Editorials
Position Statements
However
Little evidence based data
No Prospective Studies
BRONJ Incidence - variation in literature
Several acronyms:
BRON - bisphosphonate - related osteonecrosis of the jaw
BON - bisphosphonate osteonecrosis
BAONJ - bisphosphonate-associated osteonecrosis of the jaw
ONJ - osteonecrosis
No standardisation of diagnostic criteria
Variation in type of study - retrospective/ prospective
Different duration of drug exposure
Under reporting
BRONJ Incidence
No Conclusive Data
No epidemiological data in the general population
Novince 2008
Case Report
65-year-old man affected by renal cell carcinoma with bony metastases
(left femur; humeral head)
Dr Stefano Fedele DDS, PHD
Oral Medicine and Special Care Dentistry
UCL Eastman Dental Institute
TREATMENT (since 1999)
nephrectomy
subcutaneous IL-2
i.v. pamidronate
i.v. zoledronic acid (since 2003)
From 2003 to early 2004 the patient had several teeth extracted
apparently because of "ordinary" dental and periodontal diseases
From March 2004 the patient started to complain of:
continuous and intense mandibular pain
swelling in the area of the chin and floor of the mouth
progressive development of cutaneous nodules with suppuration
In July 2004 the patient was referred to the Oral Medicine Dept
SYMPTOMS:
Significant impairment of speech, eating, swallowing, associated with
chronic severe mandibular pain.
HISTOPATHOLOGICAL EXAMINATION
INFLAMMATORY CHANGES WITH NONSPECIFIC BACTERIAL SUPERINFECTION. NO
EVIDENCE OF METASTATIC DISEASE
gross bone
destruction
osteosclerotic areas
lamellated periostal
reaction
fistula tract
MANAGEMENT:
SYMPTOMATIC
THERAPY
(based on the presence of pain and signs of acute infection)
Intermittent course of antibiotics and analgesic (with
sensitivity studies)
Local application of antimicrobial agents
(chlorhexidine; hydrogen peroxide)
Irrigation of fistulas with saline
REMAINING PROBLEMS
QOL remains significantly diminished due to :
Necessity of chronic antibiotics and analgesic administration
Recurrent acute oro-facial pain
Necessity of weekly wound care
Impossibility of undergoing dental rehabilitation
BRONJ - Risk factors
Can broadly be grouped into:
Drug related
Local factors
Systemic and demographic factors
BRONJ - Risk factors
Drug related:
Dose/ potency
Zolendronic A >Pamindronate>Oral BP's
Route of administration
IV>Oral
Exposure
Zolendronic A incidence rates from1%-21% at 3yrs
Oral BP's >3yrs
Cumulative risk
<1% at 1 yr
3% after 2 yrs
11% at 4yrs
BRONJ - Risk factors
Local
Surgical procedures
Extractions in up to 80%
Anatomy
Mandible > Maxilla
Areas of thin mucosa eg, lingual ridge, exostoses
Concomitant Oral disease
Trauma
Dentures
Poor OH, periodontal/ periapical infection
BRONJ - Risk factors
Systemic and demographic factors
Age
78% > 60yrs
Gender
F > M for Oral BP's
Race
Caucasians
Systemic disease
Multiple Myeloma
Metastasizing breast and prostate cancer
Osteoporosis
Diabetes Mellitus / Rheumatoid arthritis
Drugs
Smoking/ alcohol
Coticosteroid use
Immunosuppressant use eg methotrexate, azathioprine
Antiangiogenic agents
BRONJ Pathogenesis - theories
BRONJ Pathogenesis update
Evidence suggests the necrotic tissue becomes infected as opposed to
infected tissue becoming necrotic
Remodelling suppression
Disrupted angiogenesis
Necrosis
Infection
BRONJ- Presenting features
Definition
Exposed Bone
Maxillofacial region
>8 weeks duration
Bisphosphonate exposure
No history of radiation therapy to craniofacial region
BRONJ- Presenting features
Exposed bone
Pain
Infection +/- extraoral/intraoral fistula
Traumatic ulceration 2o to sharp exposed bone
Halitosis
Paraesthesia
Fractured Mandible
BRONJ - Radiographic features
Osseus Sclerosis
Osteolysis
Periosteal new bone formation
Periapical radiolucencies
Oroantral fistula
Sequestra
BRONJ - Management
Goal - to preserve QoL
Control pain
Manage infections
Maintain function (Speech and mastication)
Prevent new areas of necrosis
Social Life (halitosis)
Patient education
Patient reassurance
(Support of continued oncological treatment)
BRONJ - Management: based on staging
PREVENTION
BRONJ Preventive Measures
incidence BRONJ with implementation of dental preventative
measures
infection rates of any non- infected already necrotic
exposed bone
Monitoring programme - improved clinical outcome with less invasive Tx
required
Retrospective and prospective studies
Dimopoulous 2008, Ripamonti 2008
BRONJ: Consensus Guidelines
IV
Consultation with oncologist
Complete necessary Dental treatment before start
If non urgent surgical treatment - consider stopping BP's for 3-6
months pre op and until healing surgical site
If treatment urgent proceed and consider BP cessation until healing
Symptomatic teeth located in already necrosed and exposed bone should
be extracted - unlikely to exacerbate
BRONJ: Consensus Guidelines
IV
Symptomatic teeth that would otherwise require extraction should
receive non surgical endo/ perio and left insitu
Avoid implants
Dental evaluation pre treatment and continued 6 monthly
BRONJ: Consensus Guidelines
ORAL
Before treatment:
Inform all patients of risks
Dental Assessment
Routine Dental Care
Treat active oral infections & risk further infections
Allow time for epithelial healing
Taking BP's:
Conservative dental treatment
No contraindication to implants - need informed consent
BRONJ Preventive Measures
Identify at risk patients - MH
Identify possible comorbidities
Diabetes
Coticosteroids
Other Immunosuppressants
Renal Disease
Refer these patients if extraction unavoidable
Dental treatment for Patients on Oral Bisphosphonates
Maintain Excellent OH - avoid excessive soft tissue injury
Diet and Fluoride Advice
Check and adjust dentures for potential soft tissue injury
For those teeth grade 3 mobile or persistently infected extraction is
necessary - as atraumatic as possible
Extractions in Patients on Oral Bisphosphonates
Risk is very small - but inform of risks
Prior to extraction rinse for one minute with Chlorhexidine
Post extraction twice daily until tissue healing
Consider suture to aid primary tissue closure
Follow up clinically - refer if chronic exposed bone
Extractions in Patients on Oral Bisphosphonates
If unexpected surgical then give post op antibiotics (Amoxycillin or
Metronidazole)
If likely surgical - refer
If multiple extractions - treat one quadrant at a time - allow healing
for 2 months