BISPHOSPHONATE RELATED OSTEONECROSIS OF THE  JAW (BRONJ)
BISPHOSPHONATES AND WHAT HAPPENS TO BONE <ul><li>VINCENT E. DIFABIO, DDS, MS MEMBER OF THE COMMITTEE ON HEALTHCARE AND ADV...
BISPHOSPHONATES AND WHAT HAPPENS TO BONE <ul><li>PRESENT THE POTENTIAL FOR A DIFFERENT ETIOLOGY OF BONE DESTRUCTION IN THE...
OSTEONECROSIS OF THE JAW <ul><li>NOT A NEW DISEASE OR PHENOMENON </li></ul><ul><li>“PHOSSY JAW” DATES BACK TO THE 19 TH  C...
BISPHOSPHONATES <ul><li>ARE USED TO TREAT SEVERAL DISEASE ENTITIES </li></ul><ul><li>OSTEOPOROSIS </li></ul><ul><li>CANCER...
OSTEOPOROSIS <ul><li>TREATED WITH BISPHOSPHONATES (BPs) </li></ul><ul><li>MANY PEOPLE WORLD WIDE ARE RECEIVING THESE TYPES...
Osteoporosis   <ul><li>Primary disease :  quantities of sex hormones </li></ul><ul><ul><li>Phase 1 : trabecular bone resor...
Osteoporosis   <ul><li>Secondary disease : consequence of other diseases or medications </li></ul><ul><ul><li>Long term st...
Osteoporosis   <ul><li>Unbalanced bone remodeling where  </li></ul><ul><li>bone formation = bone resorption </li></ul><ul>...
Osteoporosis is a BIG problem in the USA! <ul><li>Surgeon General Report (2004) </li></ul><ul><ul><li>40% of American wome...
OSTEOPOROSIS <ul><li>THE BIG QUESTION IS WILL THESE PATIENTS IN THE FUTURE DEVELOP A SIMILAR OSTEONECROSIS OF THE JAW??? <...
OSTEORADIONECROSIS <ul><li>NOTED WITH THE INTRODUCTION OF RADIATION THERAPY TO TUMORS OF THE HEAD AND NECK </li></ul><ul><...
OSTEOMYELITIS <ul><li>BACTERIAL INFECTION  OF THE BONE  </li></ul><ul><li>PRIMARY OR SECONDARY TO DENTAL OR OTHER ORAL INF...
PATHOPHYSIOLOGY <ul><li>ALTHOUGH THE OSTEORADIONECROSIS (RADIATION INDUCED), OSTEOMYELITIS (BACTERIAL INFECTION) AND BISPH...
ICD-9-CM <ul><li>WE HAVE SPECIFIC ICD-9-CM CODES FOR  OSTEOPOROSIS ,  OSTEOMYELITIS  AND  OSTEORADIONECROSIS   </li></ul><...
NEED FOR A SPECIFIC CODE  <ul><li>REPORTING INCIDENCE OF OCCURRENCE AND TRACKING </li></ul><ul><li>RESEARCH </li></ul><ul>...
BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (ONJ) <ul><li>FIRST RECOGNIZED IN 2003 AS A COMPLICATION OF BISPHOSPHONATE...
BRONJ <ul><li>CAN BE RELATED TO DENTAL TREATMENT  </li></ul><ul><li>CAN BE RELATED TO DENTAL PATHOLOGY </li></ul><ul><li>C...
PROPOSED INDUCTION MECHANISMS <ul><li>INHIBITION OF OSTEOCLAST ACTIVITY </li></ul><ul><li>REDUCES BONE TURNOVER </li></ul>...
BRONJ <ul><li>TRUE INCIDENCE IS DIFFICULT TO ESTIMATE </li></ul><ul><li>DEPENDING ON RECENT RETROSPECTIVE REPORTS COULD BE...
ONJ <ul><li>MULTIPLE PAPERS RELATING BPs WITH ONJ SINCE 2003 </li></ul><ul><li>RELATED TO METHOD OF ADMINISTRATION OF BPs:...
BP’s Mechanism of action <ul><li>1)   Tissue level </li></ul><ul><li>a .   reduction of bone turnover </li></ul><ul><li>2)...
BP’s Mechanism of action <ul><li>3)  Molecular level </li></ul><ul><ul><li>Interferes with osteoclast intercellular bioche...
Bisphosphonates <ul><li>Pharmacologic action : </li></ul><ul><li>-  Inhibition of bone resorption  </li></ul><ul><li>Pharm...
Staging <ul><li>Stage 1   </li></ul><ul><li>Characterized by exposed bone that is asymptomatic with no evidence of signifi...
Staging <ul><li>Stage 2 </li></ul><ul><li>Exposed bone associated with pain, soft tissue and/or bone infection </li></ul>
Staging <ul><li>Stage 3 </li></ul><ul><li>Pathologic fracture </li></ul><ul><li>Exposed bone associated with soft tissue i...
Staging <ul><li>Stage 3 </li></ul><ul><li>Pathologic fracture </li></ul><ul><li>Exposed bone associated with soft tissue i...
A 40 yo with female with a diagnosis of breast cancer and Zometa therapy (6 months) presents with pain, exposed and infect...
Relative Potency <ul><li>Etidronate (Didronel) 1 </li></ul><ul><li>Tiludronate (Skelide) 10 </li></ul><ul><li>Pamidronate ...
PROPOSAL <ul><li>NEW  DIAGNOSTIC   ICD-9CM  CODE FOR THE ASEPTIC NECROSIS OF BONE IN THE JAWS: </li></ul><ul><li>NEW CODE:...
Combinations  <ul><li>Use  E933.1 antineoplastic & immunosuppressive drugs and </li></ul><ul><li>May also need to Code for...
 
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BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (BRONJ)

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  • -The action of BP’s at the molecular level have not been elucidated as of yet -It has been proposed that BP’s interfere with osteoclast intercellular biochemical pathways, either by: Interacting with a cell-surface receptor or… By uptake of the BP by the osteoclast and interference with cellular metabolism -In fact, one study has recently demonstrated that BP’s interact with a receptor on the cell surface of osteoblasts, perhaps interfering with their ability to produce bone as well
  • -lastly, several in vitro studies have presented evidence that BP’s mediate osteoclast apoptosis at the in vitro
  • -Bisphosphonates, such as Aredia, Zometa, and Fosamax, are analogues of pyrophosphates whose primary mode of action is inhibition of bone resorption -These compounds accumulate in sites of increased bone deposition and resorption, where they remain for extended periods of time and are released slowly into the circulation (-low plasma levels for 2 to 28 days)
  • BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (BRONJ)

    1. 1. BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (BRONJ)
    2. 2. BISPHOSPHONATES AND WHAT HAPPENS TO BONE <ul><li>VINCENT E. DIFABIO, DDS, MS MEMBER OF THE COMMITTEE ON HEALTHCARE AND ADVOCACY FROM THE AMERICAN ASSOCIATION OF ORAL & MAXILLOFACIAL SURGERY ( AAOMS ) ASSOCIATE PROFESSOR OF ORAL & MAXILLOFACIAL SURGERY UNIVERSITY OF MARYLAND, BALTIMORE, MARYLAND AND PRIVATE PRACTICE OF ORAL & MAXILLOFACIAL SURGERY, FREDERICK, MARYLAND </li></ul>
    3. 3. BISPHOSPHONATES AND WHAT HAPPENS TO BONE <ul><li>PRESENT THE POTENTIAL FOR A DIFFERENT ETIOLOGY OF BONE DESTRUCTION IN THE MAXILLA AND MANDIBLE AND </li></ul><ul><li>THE NEED FOR SPECIFIC CODES TO REPRESENT THIS DIFFERENT ETIOLOGY OF BONE DESTRUCTION SEEN IN THE MAXILLA AND MANDIBLE </li></ul>
    4. 4. OSTEONECROSIS OF THE JAW <ul><li>NOT A NEW DISEASE OR PHENOMENON </li></ul><ul><li>“PHOSSY JAW” DATES BACK TO THE 19 TH CENTURY </li></ul><ul><li>RELATED TO MATCHSTICK MAKING </li></ul><ul><li>HIGH LEVELS OF PHOSPHORUS </li></ul>
    5. 5. BISPHOSPHONATES <ul><li>ARE USED TO TREAT SEVERAL DISEASE ENTITIES </li></ul><ul><li>OSTEOPOROSIS </li></ul><ul><li>CANCER PATIENTS </li></ul><ul><li>RECENT PAPERS HAVE SHOWN THAT A JAW OSTEONECROSIS OF ASEPTIC ETIOLOGY IS ASSOCIATED WITH THE USE OF BISPHOSPHONATES </li></ul>
    6. 6. OSTEOPOROSIS <ul><li>TREATED WITH BISPHOSPHONATES (BPs) </li></ul><ul><li>MANY PEOPLE WORLD WIDE ARE RECEIVING THESE TYPES OF MEDICATIONS </li></ul><ul><li>IS THIS TREATMENT OF OSTEOPOROSIS WITH BPs OF CONCERN??? </li></ul>
    7. 7. Osteoporosis <ul><li>Primary disease : quantities of sex hormones </li></ul><ul><ul><li>Phase 1 : trabecular bone resorption due to estrogen deficiency. Peaks after 4-8 years (women only) </li></ul></ul><ul><ul><li>Phase 2 : persistent, slower loss of both trabecular and cortical bone which is mainly due to decreased bone formation (men and women) </li></ul></ul>
    8. 8. Osteoporosis <ul><li>Secondary disease : consequence of other diseases or medications </li></ul><ul><ul><li>Long term steroid use, Cushing’s disease, anorexia nervosa, athletic amenorrhea, HPT, cystic fibrosis, inflammatory bowel disease, rheumatoid arthritis </li></ul></ul><ul><li>Observed in young/old, men/women </li></ul><ul><li>Osteoporosis ICD-9-CM Codes: 733.0 – 733.09 </li></ul>
    9. 9. Osteoporosis <ul><li>Unbalanced bone remodeling where </li></ul><ul><li>bone formation = bone resorption </li></ul><ul><li>Defined as a disease with low bone mass and deterioration of bone structure resulting in bone fragility and increase risk of fracture </li></ul><ul><li>Females >>>Males </li></ul><ul><li>Primary vs . Secondary </li></ul>Lerner AH, J. Dent Res 85. 2006
    10. 10. Osteoporosis is a BIG problem in the USA! <ul><li>Surgeon General Report (2004) </li></ul><ul><ul><li>40% of American women > 50 yo. Will experience an osteoporotic fracture </li></ul></ul><ul><ul><li>13% of men 50 yo. </li></ul></ul><ul><ul><li>By 2020 it is estimated that 50% of all Americans over the age of 50 will be at risk of developing osteoporosis </li></ul></ul><ul><ul><li>Direct cost expenditures for 1.3 million fx per yr = $14 billion + </li></ul></ul>
    11. 11. OSTEOPOROSIS <ul><li>THE BIG QUESTION IS WILL THESE PATIENTS IN THE FUTURE DEVELOP A SIMILAR OSTEONECROSIS OF THE JAW??? </li></ul>
    12. 12. OSTEORADIONECROSIS <ul><li>NOTED WITH THE INTRODUCTION OF RADIATION THERAPY TO TUMORS OF THE HEAD AND NECK </li></ul><ul><li>RADIATION CREATES HARD AND SOFT TISSUE HYPOXIA, HYPO-CELLULARITY AND HYPO-VASCULARITY </li></ul><ul><li>RESULTS IN A SIGNIFICANT DECREASE IN HEALING AND NECROSIS OF BONE </li></ul><ul><li>OSTEORADIONECROSIS OF THE JAWS ICD - 9- CM CODE: 526.89 </li></ul>
    13. 13. OSTEOMYELITIS <ul><li>BACTERIAL INFECTION OF THE BONE </li></ul><ul><li>PRIMARY OR SECONDARY TO DENTAL OR OTHER ORAL INFECTIONS </li></ul><ul><li>OSTEOMYELITIS OF THE BONE: 730 – 730.9 INCLUDES ACUTE AND CHRONIC and </li></ul><ul><li>OSTEOMYELITIS OF THE JAW: 526.4 and 526.5 </li></ul>
    14. 14. PATHOPHYSIOLOGY <ul><li>ALTHOUGH THE OSTEORADIONECROSIS (RADIATION INDUCED), OSTEOMYELITIS (BACTERIAL INFECTION) AND BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (ASEPTIC NECROSIS & DRUG INDUCED) ARE DIFFERENT IN ETIOLOGY, THEY ARE SIMILAR IN PATHOLOGY AND SECONDARY INFECTIONS </li></ul><ul><li>AND WILL THE OSTEOPOROSIS PATIENTS TREATED WITH BPs DEVELOP A SIMILAR ONJ IN THE FUTURE?? </li></ul>
    15. 15. ICD-9-CM <ul><li>WE HAVE SPECIFIC ICD-9-CM CODES FOR OSTEOPOROSIS , OSTEOMYELITIS AND OSTEORADIONECROSIS </li></ul><ul><li>SO WHY NOT USE THESE CODES FOR BP RELATED ASEPTIC OSTEONECROSIS OF THE JAW OR BRON JAW?? </li></ul>
    16. 16. NEED FOR A SPECIFIC CODE <ul><li>REPORTING INCIDENCE OF OCCURRENCE AND TRACKING </li></ul><ul><li>RESEARCH </li></ul><ul><li>EVALUATION & MANAGEMENT AND SURGICAL PROCEDURES OF MAXILLA AND MANDIBLE LINKED TO A SPECIFIC VS NON-SPECIFIC ICD-9CM CODE </li></ul>
    17. 17. BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (ONJ) <ul><li>FIRST RECOGNIZED IN 2003 AS A COMPLICATION OF BISPHOSPHONATE THERAPY </li></ul><ul><li>HIGHER FREQUENCY IN THE MANDIBLE (63%) THAN IN THE MAXILLA (38%) </li></ul><ul><li>ETIOLOGY IS UNCLEAR AND IS THE SUBJECT OF CURRENT RESEARCH AND INVESTIGATION </li></ul>
    18. 18. BRONJ <ul><li>CAN BE RELATED TO DENTAL TREATMENT </li></ul><ul><li>CAN BE RELATED TO DENTAL PATHOLOGY </li></ul><ul><li>CAN BE SPONTANEOUS WITH DENTAL ETIOLOGY </li></ul><ul><li>CAN BE RELATED TO DENTURE IRRITATION OR WEAR </li></ul><ul><li>CAN BE UNRELATED TO ANY OF THE ABOVE </li></ul><ul><li>CAN BE RELATED TO LOCAL TRAUMA </li></ul><ul><li>CAN BE UNKNOWN IN ETIOLOGY </li></ul>
    19. 19. PROPOSED INDUCTION MECHANISMS <ul><li>INHIBITION OF OSTEOCLAST ACTIVITY </li></ul><ul><li>REDUCES BONE TURNOVER </li></ul><ul><li>REDUCING REMODELING </li></ul><ul><li>DECREASED NEW BONE FORMATION </li></ul><ul><li>ETIOLOGY IS UNKNOWN </li></ul><ul><li>BUT IS LIKELY MULTIFACTORIAL </li></ul>
    20. 20. BRONJ <ul><li>TRUE INCIDENCE IS DIFFICULT TO ESTIMATE </li></ul><ul><li>DEPENDING ON RECENT RETROSPECTIVE REPORTS COULD BE <1%-9% OF CANCER PATIENTS RECEIVING BISPHOSPHONATES </li></ul><ul><li>SEEN IN CANCER PATIENTS WITH MULTIPLE ANTINEOPLASTIC MEDICATIONS AS WELL AS BISPHOSPHONATES </li></ul><ul><li>MULTIPLE MYELOMA, BREAST CANCER AND PROSTATE CANCER ARE THE PRIMARY NEOPLASMS AFFECTED </li></ul><ul><li>AND WHAT ABOUT OSTEOPOROSIS PATIENTS TREATED WITH BPs????? </li></ul>
    21. 21. ONJ <ul><li>MULTIPLE PAPERS RELATING BPs WITH ONJ SINCE 2003 </li></ul><ul><li>RELATED TO METHOD OF ADMINISTRATION OF BPs: IV VS PO </li></ul><ul><li>RELATED TO THE DURATION OF ADMINISTRATION </li></ul><ul><li>VERY SERIOUS SEQUELAE WHEN ONJ DEVELOPS </li></ul>
    22. 22. BP’s Mechanism of action <ul><li>1) Tissue level </li></ul><ul><li>a . reduction of bone turnover </li></ul><ul><li>2) Cellular level </li></ul><ul><li> a . inhibition of osteoclastic activity on the </li></ul><ul><li>bone surface (Rodan et al., Strewler) </li></ul><ul><li>b. inhibition of osteoclast recruitment on the </li></ul><ul><li>bone surface (Rodan et al., Vitte et al.) </li></ul><ul><li>c. osteoclast apoptosis (Hughes et al., Rogers et al.) </li></ul>
    23. 23. BP’s Mechanism of action <ul><li>3) Molecular level </li></ul><ul><ul><li>Interferes with osteoclast intercellular biochemical pathways </li></ul></ul><ul><ul><ul><li>Inhibition of farnesyl diphosphate synthase </li></ul></ul></ul><ul><ul><ul><li>Metabolized to toxic analogue of ATP (non-nitrogen containing BP’s) </li></ul></ul></ul>Strewler GJ. N Engl J Med 2004;350:1174
    24. 24. Bisphosphonates <ul><li>Pharmacologic action : </li></ul><ul><li>- Inhibition of bone resorption </li></ul><ul><li>Pharmacokinetics : </li></ul><ul><li>- Distribution : Rapid accumulation in sites of increased bone deposition/resorption, low plasma levels, ½ life of “years” </li></ul><ul><li>- Metabolism : Not metabolized (nitrogen containing) </li></ul><ul><li>- Excretion : Renal </li></ul>
    25. 25. Staging <ul><li>Stage 1 </li></ul><ul><li>Characterized by exposed bone that is asymptomatic with no evidence of significant soft tissue infection </li></ul>
    26. 26. Staging <ul><li>Stage 2 </li></ul><ul><li>Exposed bone associated with pain, soft tissue and/or bone infection </li></ul>
    27. 27. Staging <ul><li>Stage 3 </li></ul><ul><li>Pathologic fracture </li></ul><ul><li>Exposed bone associated with soft tissue infection or pain that is not manageable with antibiotics due to the large volume of necrotic bone. </li></ul>
    28. 28. Staging <ul><li>Stage 3 </li></ul><ul><li>Pathologic fracture </li></ul><ul><li>Exposed bone associated with soft tissue infection or pain that is not manageable with antibiotics due to the large volume of necrotic bone. </li></ul>
    29. 29. A 40 yo with female with a diagnosis of breast cancer and Zometa therapy (6 months) presents with pain, exposed and infected maxillary bone following extraction
    30. 30. Relative Potency <ul><li>Etidronate (Didronel) 1 </li></ul><ul><li>Tiludronate (Skelide) 10 </li></ul><ul><li>Pamidronate (Aredia) 100 </li></ul><ul><li>Alendronate (Fosamax) 1,000 </li></ul><ul><li>Risedronate (Actonel) 10,000 </li></ul><ul><li>Ibandronate (Boniva) 10,000 </li></ul><ul><li>Zolendronic acid (Zometa) >100,000 </li></ul>
    31. 31. PROPOSAL <ul><li>NEW DIAGNOSTIC ICD-9CM CODE FOR THE ASEPTIC NECROSIS OF BONE IN THE JAWS: </li></ul><ul><li>NEW CODE: 733.45 JAW (MAXILLA AND MANDIBLE) AND </li></ul><ul><li>APPROPRIATE NEW E CODES TO IDENTIFY THE SPECIFIC ROUTE OF ADMINISTRATION </li></ul><ul><li>E933.6 ORAL BISPHOSPHONATES AND E933.7 INTRAVENOUS BISPHOSPHONATES </li></ul>
    32. 32. Combinations <ul><li>Use E933.1 antineoplastic & immunosuppressive drugs and </li></ul><ul><li>May also need to Code for the primary neoplasm (most common ones are prostate, breast and myeloma) </li></ul>

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