Dr Alison Dougall

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Bis-phosphonates update

• Dr Alison Dougall
• Consultant for Medically Compromised Patients
• Dublin Dental School and Hospital

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• Fear
• Confusion
• Uncertainty
• Risk
• Panic
• Warning
• Litigation

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PATIENT WARNING avoid invasive dentistry!!!
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How much do we need to know?
Jump into unknown Trouble
Fear Neglect
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1st Generation oral bisphosphonates

• Introduced in 1990s
• Improve bone quality in Pagets Disease
• Osteoporosis
• Alternative to HRT in post menopause women
• Prevent fractures of spine, wrist and hip
• 2ndry to corticosteroid use, SLE, RA,
• Injectables introduced for pts with dosing
  difficulties, inability to sit upright for 60
  mins or swallow tablets

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2nd and 3rd Generation IV bisphosphonates

• Hypercalcaemia of malignancy
• Prevent metastatic tumours in breast, lung and
  prostate cancer
• Prevent bone complications and pain in multiple
  myeloma and kidney disease
• Prevent post-operative fractures and weakness in
  kidney, liver and cardiac transplant patients

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Wonder Drug?

• 19th most prescribed drug group worldwide
• Synthetic analogues of pyrophosphates
• Not metabolised
• ½ absorbed dose is distributed to bone
• Increase bone density and thickness
• Prevent tumours from removing bone and spreading
• Inhibit differentiation of bone marrow cells into
  osteoclasts
• Inhibit Osteoclast activity
• Reduction in bone turnover and resorption
• Reduce local release of factors that stimulate
  tumour growth

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Side effects

• Osteoclast function severely impaired
• Osteocytes not repaced
• Capillary network in bone not maintained
• Bone becomes too dense choking capillary network
• Avascular bone necrosis
• Osteonecrosis
• Osteochemonecrosis
• BON, ONJ

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Incidence of ONJ in maxilla and mandible

• 3000 world cases
• (191 million prescriptions)
• Mostly associated with intra-venous
  bis-phosphonates
• Zometa (Zoledronic Acid)
• Aredia (Palmidronate)
• Mostly following dental extractions or
  periodontal surgery
• Some spontaneously
• Chronic infection
• Trauma

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Risk factors

• IV Bisphosphonate higher risk for BON
• 50 of dose is bio available for bone matrix
• Oral bis-phosphonate low risk for BON
• 1 dose of is absorbed by GI Tract
• Recent assessment test for necrosis potential
• Arun Garg/Marx - Miami
• C-Terminal Telopeptide (CTX) - marker for serum
  bone turnover
• scores - controversial
• Time
• Half life is 8-10 years

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Co-risk problems

• Immune-suppression
• Diabetes
• HIV
• Leukaemia
• Transplants
• Drug Therapy
• Corticosteroids
• Chemo-therapy
• Immune suppressants
• Age
• SLE, RA auto-immune diseases
• Clotting Disorders
• Sickle cell Disease

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Why a dental problem?

• Bis Ph. accumulate in high turnover areas
• Higher concentrations of drug in mandible than
  elsewhere
• After trauma or infection bone cannot respond
  adequately
• Masticatory Forces
• Chronic Low Grade Trauma
• Unable to repair micro-fractures
• Necrotic Bone
• Bony sequestrum

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Clinical Presentation

• Delayed or absent healing after extractions
• Ragged Ulceration with bony base
• Exposed or denuded bone
• May be symptomless unless 2ndry infection
• Mobile Teeth may mimic periodontal disease
• Bone Pain
• Chronic Pain
• Heavy Jaw
• Numbness
• Ref. to oral medicine clinic/Max Fax

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Spontaneous necrosis in periodontal disease
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Trauma from denture flange
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Denuded mandibular torus
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Presenting Complaint ulceration gt3 months
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Following extraction
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Treatment

• Clinical Management based on expert opinion
• No evidence base yet
• Most post op treatment not effective
• Antibiotics
• Withdrawing bis-phosphonate therapy
• Hyperbaric oxygen
• Surgical resection of necrotic bone
• Prevention is best option
• Dental screening before patient commences drug
  therapy

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www.education!!!

• Education
• Patient
  http//www.ada.org/public/topics/osteonecrosis.
  asp
• Dental Team
  
  www.jada.ada.org
• Oncologists/Medical Profession
  www.jopasco.org
• Practical Guidelines for treatment of
  osteonecrosis in patients with cancer. Journal of
  Oncology Practice 2006 Vol 2 Issue 1

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Practice Points
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Special Care Patients

• Medical History
• Likely Pt groups
• Post menopausal women
• Patients with history of hip fractures
• Osteoporosis
• Pagets Disease
• Breast cancer
• Prostate Cancer
• Lung Cancer
• Multiple myeloma
• Transplant Patients
• Kidney Failure/Dialysis

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Drug History/Route

• Oral Bisphosphonates daily tablets
• Actonel (Risendronate)
• Boniva (Ibandronate)
• Didronel (Etidronate)
• Fossamax (alendronate)
• Skelid (Tiludronate)
• IV Bisphosphonates monthly injections
• Zometa (Zoledronate)
• Aredia) (Pamidronate)
• Bonefos/Loron (Clodronate)
• Important to know how long drug has been taken

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Fossamax

• 13th most prescribed drug in the world
• 170 cases BON worldwide (since 2006)
• No true cause-effect relationship
• Extremely Low Risk BON
• 0.7 cases per 100,000 person years exposure

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Dental management of patients receiving oral
bisphosphonate therapy

• www.ada.org/prof/resources/topics/osteonecrosis.as
  p
• Dentist should inform pt that low risk of
  developing BON
• Ways to minimise risk but not eliminate it
• Good oral hygiene with regular dental care is
  best way to lower the risk
• Patients shown how to screen their mouths for
  signs
• Routine dental treatment should not be modified
• Alternatives to extractions should be offered
• Non surgical periodontal management preferred
• Care with fit of dentures

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Fossamax 8 years
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Oral Surgery/Perio surgery

• Do not stop bis-phosphonate therapy
• Informed Consent Form
• ADA website has template
• Chlorhexidine rinse pre-op
• Limit extraction or perio surgery to one sextant
• Suture to prevent soft tissue trauma
• Avoid packing surgicell etc
• Irrigation of socket with chlorhexidine post-op
• No further surgery for two months to assess
  healing
• Care with trauma from immediate dentures/splints
• Post-op antibiotics only if co-risk factors
• Metronidazole 200mg tds for five days
• Amoxycillin 500mg TDS for fourteen days
• Or clinadamycin 300mg TDS for fourteen days

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Aids to prevention

• Inform patient of the consequences of oral
  neglect
• Xerostomia
• Professionally applied products
• Cervitec
• 1 Chlorhexidine
• 1 thymol
• Home applied products
• GC Tooth mousse
• Water Soluble mousse
• Buffer which neutralises acidic saliva
• Recaldent (Amorphous Calcium Phosphate)
• Aids remineralisation
• Applied with finger once per day

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Dental management of patients receiving iv
bisphosphonate therapy

• Patients at higher risk of developing BON
• Routine care as per oral bisphosphonate therapy
• Tori high risk area for trauma
• Regular hygienist input encouraged but care with
  mechanical intrumentation
• Accidental trauma recommend soft
  toothbrush/changed often
• Avoid extractions and periodontal surgery if at
  all possible
• Implants contra-indicated
• Endodontics encouraged

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Risk assess surgery each case

• risk of developing BON higher with time
• risk of developing spontaneous BON higher in
  presence of infection
• risk of developing spontaneous BON higher in
  presence of periodontal disease (grade 3 mobile)
• Risk greatest in mandible
• Risk of developing BON higher with co-factors

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Guidance for practitioners

• Expert Panel JADA August 2006
• No data from Clinical trials
• Strict regime of post-op antimicrobials and
  antibiotics (anecdotal)
• To prevent secondary infection
• No withdrawing of drug pre-operatively unless
  specified locally
• Maximum 1-2 teeth extracted in one visit
• Wait 2 months before repeat surgery

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Dr Doctor

• Liase with oncologist
• Information about the need for surgery
• risks of providing and not providing care
• Regime that you plan to use pre/peri and post op
• Whether oncolgist would prefer to reduce/withdraw
  drug pre or post operatively
• FBC check platelets
• Consent
• Patients informed of risks involved with
  providing and not providing treatment
• Be honest it is a gamble until the research is
  in place
• Involve the patient in the decisions.
• Patient takes some responsibility for their
  dental problem

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Zometa 3 months post ca breast
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Pain and sinus LR6

• Elective extraction
• IV bisphosphonates lower risk for first 3-6
  months
• Patient finished chemo therapy
• Protocol
• Pre-op
• Liase with oncologist
• FBC
• Consent
• Peri-op
• Pre-op chlorhexidine rinse
• LA with adrenaline
• No flap raised
• De-coronated tooth sectioned and elevated roots
• Post op
• Suturing to avoid trauma to soft tissues, vicryl
• No packing (surgicell)
• Metronidazole 200mg TDS for 5 days
• 250-500mg amoxycilin TDS for up to two months

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Patient and dentist relieved

• Patient irrigates socket with chlorhexidine BD
  for two months
• Review
• 2 weeks
• 1 month
• 2 months
• Healed well with no complications
• Anecdotally, lower incidence of BON than expected
  in patients with few co-factors

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2 months post extraction
Grade 3 mobile tooth
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Chlorhexidine BD for three months Amoxycillin
250mg for two months
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Soft Tissue crown lenthening
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Bony Sequestrum and Healing

• Non-invasive management
• Metronidazole and amoxycillin
• Chlorhexidine
• 2 -3 months healing time
• Patients given syringe and instructed to clean
• Sequestrum tweezered out in time

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Endodontics

• Extremely high risk cancer patient
• No symptoms
• XLA LR3 unavoidable
• Endodontics LR12
• No instrumentation of apex
• Corsodyl post op (rubber dam)
• Decoronating and seal to avoid soft tissue
  injuries
• /- Antibiotics
• Fingers crossed

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Difficult Scenarios highlighting problems to
medics

• Male aged 52
• Swelling LLQ
• Multiple Myeloma
• Diabetes
• Undergoing chemo therapy
• IV Bisphosphonate for 18 months
• Post-extraction developed osteochemonecrosis LLQ
• Life saving bone marrow transplant delayed
• Oncologists have initiated dental screening
  programme and information leaflets for patients

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Future

• Risk of treating patients taking oral
  bisphosphonates is small!!
• Will this increase in time (long half life)
• Price of dental neglect due to fear is high
• Regular routine and preventive care essential
• Perceived increased need for services of
  endodontists
• Most cases of BON occur in high risk patients
  taking high risk drugs after dental surgery
• Guidelines updated regularly
• Comprehensive oral evaluation on patients
  starting therapy
• New generation of effective drugs avoiding BON

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Thank you for listening Notes available on ISDH
website soon