Bisphosphonates Update by Alison Dougal

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Bisphosphonates Update by Alison Dougal

  1. 1. Dr Alison Dougall Consultant for Medically Compromised Patients Dublin Dental School and Hospital Bis-phosphonates update
  2. 2. <ul><li>Fear </li></ul><ul><li>Confusion </li></ul><ul><li>Uncertainty </li></ul><ul><li>Risk </li></ul><ul><li>Panic </li></ul><ul><li>Warning </li></ul><ul><li>Litigation </li></ul>
  3. 3. PATIENT WARNING : avoid invasive dentistry!!!
  4. 4. How much do we need to know? Jump into unknown = T rouble Fear = N eglect
  5. 5. 1 st Generation – oral bisphosphonates <ul><li>Introduced in 1990’s </li></ul><ul><li>Improve bone quality in Pagets Disease </li></ul><ul><li>Osteoporosis </li></ul><ul><ul><li>Alternative to HRT in post menopause women </li></ul></ul><ul><ul><li>Prevent fractures of spine, wrist and hip </li></ul></ul><ul><ul><li>2ndry to corticosteroid use, SLE, RA, </li></ul></ul><ul><li>Injectables introduced for pts with dosing difficulties, inability to sit upright for 60 mins or swallow tablets </li></ul>
  6. 6. 2 nd and 3 rd Generation – IV bisphosphonates <ul><li>Hypercalcaemia of malignancy </li></ul><ul><li>Prevent metastatic tumours in breast, lung and prostate cancer </li></ul><ul><li>Prevent bone complications and pain in multiple myeloma and kidney disease </li></ul><ul><li>Prevent post-operative fractures and weakness in kidney, liver and cardiac transplant patients </li></ul>
  7. 7. Wonder Drug? <ul><li>19 th most prescribed drug group worldwide </li></ul><ul><li>Synthetic analogues of pyrophosphates </li></ul><ul><li>Not metabolised </li></ul><ul><li>½ absorbed dose is distributed to bone </li></ul><ul><li>Increase bone density and thickness </li></ul><ul><li>Prevent tumours from removing bone and spreading </li></ul><ul><ul><li>Inhibit differentiation of bone marrow cells into osteoclasts </li></ul></ul><ul><ul><li>Inhibit Osteoclast activity </li></ul></ul><ul><ul><li>Reduction in bone turnover and resorption </li></ul></ul><ul><ul><li>Reduce local release of factors that stimulate tumour growth </li></ul></ul>
  8. 8. Side effects <ul><li>Osteoclast function severely impaired </li></ul><ul><li>Osteocytes not repaced </li></ul><ul><li>Capillary network in bone not maintained </li></ul><ul><li>Bone becomes too dense choking capillary network </li></ul><ul><li>Avascular bone necrosis </li></ul><ul><li>Osteonecrosis </li></ul><ul><li>Osteochemonecrosis </li></ul><ul><li>BON, ONJ </li></ul>
  9. 9. Incidence of ONJ in maxilla and mandible <ul><li>3000 world cases </li></ul><ul><ul><li>(191 million prescriptions) </li></ul></ul><ul><li>Mostly associated with intra-venous bis-phosphonates </li></ul><ul><ul><li>Zometa (Zoledronic Acid) </li></ul></ul><ul><ul><li>Aredia (Palmidronate) </li></ul></ul><ul><li>Mostly following dental extractions or periodontal surgery </li></ul><ul><li>Some spontaneously </li></ul><ul><ul><li>Chronic infection </li></ul></ul><ul><ul><li>Trauma </li></ul></ul>
  10. 10. Risk factors <ul><li>IV Bisphosphonate = higher risk for BON </li></ul><ul><ul><li>50% of dose is bio available for bone matrix </li></ul></ul><ul><li>Oral bis-phosphonate = low risk for BON </li></ul><ul><ul><li>1% dose of is absorbed by GI Tract </li></ul></ul><ul><li>Recent assessment test for necrosis potential </li></ul><ul><ul><li>Arun Garg/Marx - Miami </li></ul></ul><ul><ul><li>C-Terminal Telopeptide (CTX) -– marker for serum bone turnover </li></ul></ul><ul><ul><li>scores - controversial </li></ul></ul><ul><li>Time </li></ul><ul><ul><li>Half life is 8-10 years </li></ul></ul>
  11. 11. Co-risk problems <ul><ul><li>Immune-suppression </li></ul></ul><ul><ul><ul><li>Diabetes </li></ul></ul></ul><ul><ul><ul><li>HIV </li></ul></ul></ul><ul><ul><ul><li>Leukaemia </li></ul></ul></ul><ul><ul><ul><li>Transplants </li></ul></ul></ul><ul><ul><li>Drug Therapy </li></ul></ul><ul><ul><ul><li>Corticosteroids </li></ul></ul></ul><ul><ul><ul><li>Chemo-therapy </li></ul></ul></ul><ul><ul><ul><li>Immune suppressants </li></ul></ul></ul><ul><ul><li>Age </li></ul></ul><ul><ul><li>SLE, RA & auto-immune diseases </li></ul></ul><ul><ul><li>Clotting Disorders </li></ul></ul><ul><ul><li>Sickle cell Disease </li></ul></ul>
  12. 12. Why a dental problem? <ul><li>Bis Ph. accumulate in high turnover areas </li></ul><ul><li>Higher concentrations of drug in mandible than elsewhere </li></ul><ul><li>After trauma or infection bone cannot respond adequately </li></ul><ul><li>Masticatory Forces </li></ul><ul><ul><li>Chronic Low Grade Trauma </li></ul></ul><ul><ul><li>Unable to repair micro-fractures </li></ul></ul><ul><li>Necrotic Bone </li></ul><ul><li>Bony sequestrum </li></ul>
  13. 13. Clinical Presentation <ul><li>Delayed or absent healing after extractions </li></ul><ul><li>Ragged Ulceration with bony base </li></ul><ul><li>Exposed or denuded bone </li></ul><ul><ul><li>May be symptomless unless 2ndry infection </li></ul></ul><ul><li>Mobile Teeth – may mimic periodontal disease </li></ul><ul><li>Bone Pain </li></ul><ul><ul><li>Chronic Pain </li></ul></ul><ul><ul><li>Heavy Jaw </li></ul></ul><ul><ul><li>Numbness </li></ul></ul><ul><li>Ref. to oral medicine clinic/Max Fax </li></ul>
  14. 14. Spontaneous necrosis in periodontal disease
  15. 15. Trauma from denture flange
  16. 16. Denuded mandibular torus
  17. 17. Presenting Complaint ulceration >3 months
  18. 18. Following extraction
  19. 21. Treatment <ul><li>Clinical Management based on expert opinion </li></ul><ul><li>No evidence base yet </li></ul><ul><li>Most post op treatment not effective </li></ul><ul><ul><li>Antibiotics </li></ul></ul><ul><ul><li>Withdrawing bis-phosphonate therapy </li></ul></ul><ul><ul><li>Hyperbaric oxygen </li></ul></ul><ul><ul><li>Surgical resection of necrotic bone </li></ul></ul><ul><li>Prevention is best option </li></ul><ul><li>Dental screening before patient commences drug therapy </li></ul>
  20. 22. www.education!!! <ul><li>Education </li></ul><ul><ul><li>Patient http:// www.ada.org/public/topics/osteonecrosis.asp </li></ul></ul><ul><ul><li>Dental Team www.jada.ada.org </li></ul></ul><ul><ul><li>Oncologists/Medical Profession www.jopasco.org </li></ul></ul><ul><ul><li>Practical Guidelines for treatment of osteonecrosis in patients with cancer. Journal of Oncology Practice 2006 Vol 2 Issue 1 </li></ul></ul>
  21. 23. Practice Points
  22. 24. Special Care Patients <ul><li>Medical History </li></ul><ul><ul><li>Likely Pt groups </li></ul></ul><ul><ul><ul><li>Post menopausal women </li></ul></ul></ul><ul><ul><ul><li>Patients with history of hip fractures </li></ul></ul></ul><ul><ul><ul><li>Osteoporosis </li></ul></ul></ul><ul><ul><ul><li>Pagets Disease </li></ul></ul></ul><ul><ul><ul><li>Breast cancer </li></ul></ul></ul><ul><ul><ul><li>Prostate Cancer </li></ul></ul></ul><ul><ul><ul><li>Lung Cancer </li></ul></ul></ul><ul><ul><ul><li>Multiple myeloma </li></ul></ul></ul><ul><ul><ul><li>Transplant Patients </li></ul></ul></ul><ul><ul><ul><li>Kidney Failure/Dialysis </li></ul></ul></ul>
  23. 25. Drug History/Route <ul><li>Oral Bisphosphonates – daily tablets </li></ul><ul><ul><li>Actonel (Risendronate) </li></ul></ul><ul><ul><li>Boniva (Ibandronate) </li></ul></ul><ul><ul><li>Didronel (Etidronate) </li></ul></ul><ul><ul><li>Fossamax (alendronate) </li></ul></ul><ul><ul><li>Skelid (Tiludronate) </li></ul></ul><ul><li>IV Bisphosphonates – monthly injections </li></ul><ul><ul><li>Zometa® (Zoledronate) </li></ul></ul><ul><ul><li>Aredia®) (Pamidronate) </li></ul></ul><ul><ul><li>Bonefos®/Loron® (Clodronate) </li></ul></ul><ul><li>Important to know how long drug has been taken </li></ul>
  24. 26. Fossamax <ul><li>13 th most prescribed drug in the world </li></ul><ul><li>170 cases BON worldwide (since 2006) </li></ul><ul><li>No true cause-effect relationship </li></ul><ul><li>Extremely Low Risk BON </li></ul><ul><li>0.7 cases per 100,000 person years exposure </li></ul>
  25. 27. Dental management of patients receiving oral bisphosphonate therapy <ul><li>www.ada.org/prof/resources/topics/osteonecrosis.asp </li></ul><ul><li>Dentist should inform pt that low risk of developing BON </li></ul><ul><li>Ways to minimise risk but not eliminate it </li></ul><ul><li>Good oral hygiene with regular dental care is best way to lower the risk </li></ul><ul><li>Patients shown how to screen their mouths for signs </li></ul><ul><li>Routine dental treatment should not be modified </li></ul><ul><li>Alternatives to extractions should be offered </li></ul><ul><li>Non surgical periodontal management preferred </li></ul><ul><li>Care with fit of dentures </li></ul>
  26. 28. Fossamax – 8 years
  27. 29. Oral Surgery/Perio surgery <ul><li>Do not stop bis-phosphonate therapy </li></ul><ul><li>Informed Consent Form </li></ul><ul><ul><li>ADA website has template </li></ul></ul><ul><li>Chlorhexidine rinse pre-op </li></ul><ul><li>Limit extraction or perio surgery to one sextant </li></ul><ul><li>Suture to prevent soft tissue trauma </li></ul><ul><li>Avoid packing – surgicell etc </li></ul><ul><li>Irrigation of socket with chlorhexidine post-op </li></ul><ul><li>No further surgery for two months to assess healing </li></ul><ul><li>Care with trauma from immediate dentures/splints </li></ul><ul><li>Post-op antibiotics only if co-risk factors </li></ul><ul><ul><li>Metronidazole 200mg tds for five days </li></ul></ul><ul><ul><li>Amoxycillin 500mg TDS for fourteen days </li></ul></ul><ul><ul><li>Or clinadamycin 300mg TDS for fourteen days </li></ul></ul>
  28. 30. Aids to prevention <ul><li>Inform patient of the consequences of oral neglect </li></ul><ul><li>Xerostomia </li></ul><ul><li>Professionally applied products </li></ul><ul><ul><li>Cervitec </li></ul></ul><ul><ul><ul><li>1% Chlorhexidine </li></ul></ul></ul><ul><ul><ul><li>1% thymol </li></ul></ul></ul><ul><li>Home applied products </li></ul><ul><ul><li>GC Tooth mousse </li></ul></ul><ul><ul><ul><li>Water Soluble mousse </li></ul></ul></ul><ul><ul><ul><li>Buffer which neutralises acidic saliva </li></ul></ul></ul><ul><ul><ul><li>Recaldent (Amorphous Calcium Phosphate) </li></ul></ul></ul><ul><ul><ul><li>Aids remineralisation </li></ul></ul></ul><ul><ul><ul><li>Applied with finger once per day </li></ul></ul></ul>
  29. 31. <ul><li>Patients at higher risk of developing BON </li></ul><ul><li>Routine care as per oral bisphosphonate therapy </li></ul><ul><li>Tori – high risk area for trauma </li></ul><ul><li>Regular hygienist input encouraged but care with mechanical intrumentation </li></ul><ul><li>Accidental trauma – recommend soft toothbrush/changed often </li></ul><ul><li>Avoid extractions and periodontal surgery if at all possible </li></ul><ul><li>Implants contra-indicated </li></ul><ul><li>Endodontics encouraged </li></ul>Dental management of patients receiving iv bisphosphonate therapy
  30. 32. <ul><ul><li>risk of developing BON higher with time </li></ul></ul><ul><ul><li>risk of developing spontaneous BON higher in presence of infection </li></ul></ul><ul><ul><li>risk of developing spontaneous BON higher in presence of periodontal disease (grade 3 mobile) </li></ul></ul><ul><ul><li>Risk greatest in mandible </li></ul></ul><ul><ul><li>Risk of developing BON higher with co-factors </li></ul></ul>Risk assess surgery each case
  31. 33. Guidance for practitioners <ul><li>Expert Panel JADA August 2006 </li></ul><ul><li>No data from Clinical trials </li></ul><ul><li>Strict regime of post-op antimicrobials and antibiotics (anecdotal) </li></ul><ul><ul><li>To prevent secondary infection </li></ul></ul><ul><li>No withdrawing of drug pre-operatively unless specified locally </li></ul><ul><li>Maximum 1-2 teeth extracted in one visit </li></ul><ul><li>Wait 2 months before repeat surgery </li></ul>
  32. 34. Dr Doctor <ul><li>Liase with oncologist </li></ul><ul><ul><li>Information about the need for surgery </li></ul></ul><ul><ul><ul><li>risks of providing and not providing care </li></ul></ul></ul><ul><ul><ul><li>Regime that you plan to use pre/peri and post op </li></ul></ul></ul><ul><ul><ul><li>Whether oncolgist would prefer to reduce/withdraw drug pre or post operatively </li></ul></ul></ul><ul><ul><ul><li>FBC – check platelets </li></ul></ul></ul><ul><li>Consent </li></ul><ul><ul><li>Patients informed of risks involved with providing and not providing treatment </li></ul></ul><ul><ul><li>Be honest –it is a gamble until the research is in place </li></ul></ul><ul><ul><li>Involve the patient in the decisions. </li></ul></ul><ul><ul><li>Patient takes some responsibility for their dental problem </li></ul></ul>
  33. 35. Zometa 3 months – post ca breast
  34. 36. Pain and sinus LR6 <ul><li>Elective extraction </li></ul><ul><ul><li>IV bisphosphonates lower risk for first 3-6 months </li></ul></ul><ul><ul><li>Patient finished chemo therapy </li></ul></ul><ul><li>Protocol </li></ul><ul><ul><li>Pre-op </li></ul></ul><ul><ul><ul><li>Liase with oncologist </li></ul></ul></ul><ul><ul><ul><li>FBC </li></ul></ul></ul><ul><ul><ul><li>Consent </li></ul></ul></ul><ul><ul><li>Peri-op </li></ul></ul><ul><ul><ul><li>Pre-op chlorhexidine rinse </li></ul></ul></ul><ul><ul><ul><li>LA with adrenaline </li></ul></ul></ul><ul><ul><ul><li>No flap raised </li></ul></ul></ul><ul><ul><ul><li>De-coronated tooth sectioned and elevated roots </li></ul></ul></ul><ul><ul><li>Post op </li></ul></ul><ul><ul><ul><li>Suturing to avoid trauma to soft tissues, vicryl </li></ul></ul></ul><ul><ul><ul><li>No packing (surgicell) </li></ul></ul></ul><ul><ul><ul><li>Metronidazole 200mg TDS for 5 days </li></ul></ul></ul><ul><ul><ul><li>250-500mg amoxycilin TDS for up to two months </li></ul></ul></ul>
  35. 37. Patient and dentist relieved <ul><li>Patient irrigates socket with chlorhexidine BD for two months </li></ul><ul><li>Review </li></ul><ul><ul><li>2 weeks </li></ul></ul><ul><ul><li>1 month </li></ul></ul><ul><ul><li>2 months </li></ul></ul><ul><li>Healed well with no complications </li></ul><ul><li>Anecdotally, lower incidence of BON than expected in patients with few co-factors </li></ul>
  36. 38. Grade 3 mobile tooth 2 months post extraction
  37. 39. Chlorhexidine BD for three months Amoxycillin 250mg for two months
  38. 40. Soft Tissue – crown lenthening
  39. 41. Bony Sequestrum and Healing <ul><li>Non-invasive management </li></ul><ul><li>Metronidazole and amoxycillin </li></ul><ul><li>Chlorhexidine </li></ul><ul><li>2 -3 months healing time </li></ul><ul><li>Patients given syringe and instructed to clean </li></ul><ul><li>Sequestrum tweezered out in time </li></ul>
  40. 42. Endodontics <ul><li>Extremely high risk cancer patient </li></ul><ul><li>No symptoms </li></ul><ul><li>XLA LR3 unavoidable </li></ul><ul><li>Endodontics LR12 </li></ul><ul><ul><li>No instrumentation of apex </li></ul></ul><ul><ul><li>Corsodyl post op (rubber dam) </li></ul></ul><ul><ul><li>Decoronating and seal to avoid soft tissue injuries </li></ul></ul><ul><ul><li>+/- Antibiotics </li></ul></ul><ul><ul><li>Fingers crossed </li></ul></ul>
  41. 43. Difficult Scenarios highlighting problems to medics <ul><li>Male aged 52 </li></ul><ul><li>Swelling LLQ </li></ul><ul><li>Multiple Myeloma </li></ul><ul><li>Diabetes </li></ul><ul><li>Undergoing chemo therapy </li></ul><ul><li>IV Bisphosphonate for 18 months </li></ul><ul><li>Post-extraction developed osteochemonecrosis LLQ </li></ul><ul><li>Life saving bone marrow transplant delayed </li></ul><ul><li>Oncologists have initiated dental screening programme and information leaflets for patients </li></ul>
  42. 44. Future <ul><li>Risk of treating patients taking oral bisphosphonates is small!! </li></ul><ul><li>Will this increase in time (long half life) </li></ul><ul><li>Price of dental neglect due to fear is high </li></ul><ul><li>Regular routine and preventive care essential </li></ul><ul><li>Perceived increased need for services of endodontists </li></ul><ul><li>Most cases of BON occur in high risk patients taking high risk drugs after dental surgery </li></ul><ul><li>Guidelines updated regularly </li></ul><ul><li>Comprehensive oral evaluation on patients starting therapy </li></ul><ul><li>New generation of effective drugs avoiding BON </li></ul>
  43. 45. Thank you for listening Notes available on ISDH website soon

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