BISPHOSPHONATE RELATEDOSTEONECROSIS OF THE .ppt

1、BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (BRONJ),BISPHOSPHONATES AND WHAT HAPPENS TO BONE,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 UN

2、IVERSITY OF MARYLAND, BALTIMORE, MARYLAND AND PRIVATE PRACTICE OF ORAL & MAXILLOFACIAL SURGERY, FREDERICK, MARYLAND,BISPHOSPHONATES AND WHAT HAPPENS TO BONE,PRESENT THE POTENTIAL FOR A DIFFERENT ETIOLOGY OF BONE DESTRUCTION IN THE MAXILLA AND MANDIBLE AND THE NEED FOR SPECIFIC CODES TO REPRESENT THI

3、S DIFFERENT ETIOLOGY OF BONE DESTRUCTION SEEN IN THE MAXILLA AND MANDIBLE,OSTEONECROSIS OF THE JAW,NOT A NEW DISEASE OR PHENOMENON “PHOSSY JAW” DATES BACK TO THE 19TH CENTURY RELATED TO MATCHSTICK MAKING HIGH LEVELS OF PHOSPHORUS,BISPHOSPHONATES,ARE USED TO TREAT SEVERAL DISEASE ENTITIES OSTEOPOROSI

4、S CANCER PATIENTS RECENT PAPERS HAVE SHOWN THAT A JAW OSTEONECROSIS OF ASEPTIC ETIOLOGY IS ASSOCIATED WITH THE USE OF BISPHOSPHONATES,OSTEOPOROSIS,TREATED WITH BISPHOSPHONATES (BPs) MANY PEOPLE WORLD WIDE ARE RECEIVING THESE TYPES OF MEDICATIONS IS THIS TREATMENT OF OSTEOPOROSIS WITH BPs OF CONCERN?

5、,Osteoporosis,Primary disease: quantities of sex hormones Phase 1: trabecular bone resorption due to estrogen deficiency. Peaks after 4-8 years (women only) Phase 2: persistent, slower loss of both trabecular and cortical bone which is mainly due to decreased bone formation (men and women),Osteoporo

6、sis,Secondary disease: consequence of other diseases or medications Long term steroid use, Cushings disease, anorexia nervosa, athletic amenorrhea, HPT, cystic fibrosis, inflammatory bowel disease, rheumatoid arthritisObserved in young/old, men/women Osteoporosis ICD-9-CM Codes: 733.0 733.09,Osteopo

7、rosis,Unbalanced bone remodeling where bone formation = bone resorption Defined as a disease with low bone mass and deterioration of bone structure resulting in bone fragility and increase risk of fracture Females Males Primary vs. Secondary,Lerner AH, J. Dent Res 85. 2006,Osteoporosis is a BIG prob

8、lem in the USA!,Surgeon General Report (2004) 40% of American women 50 yo. Will experience an osteoporotic fracture 13% of men 50 yo. By 2020 it is estimated that 50% of all Americans over the age of 50 will be at risk of developing osteoporosis Direct cost expenditures for 1.3 million fx per yr = $

9、14 billion +,OSTEOPOROSIS,THE BIG QUESTION IS WILL THESE PATIENTS IN THE FUTURE DEVELOP A SIMILAR OSTEONECROSIS OF THE JAW?,OSTEORADIONECROSIS,NOTED WITH THE INTRODUCTION OF RADIATION THERAPY TO TUMORS OF THE HEAD AND NECK RADIATION CREATES HARD AND SOFT TISSUE HYPOXIA, HYPO-CELLULARITY AND HYPO-VAS

10、CULARITY RESULTS IN A SIGNIFICANT DECREASE IN HEALING AND NECROSIS OF BONE OSTEORADIONECROSIS OF THE JAWS ICD - 9- CM CODE: 526.89,OSTEOMYELITIS,BACTERIAL INFECTION OF THE BONE PRIMARY OR SECONDARY TO DENTAL OR OTHER ORAL INFECTIONS OSTEOMYELITIS OF THE BONE: 730 730.9 INCLUDES ACUTE AND CHRONIC and

11、 OSTEOMYELITIS OF THE JAW: 526.4 and 526.5,PATHOPHYSIOLOGY,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 SECON

12、DARY INFECTIONS AND WILL THE OSTEOPOROSIS PATIENTS TREATED WITH BPs DEVELOP A SIMILAR ONJ IN THE FUTURE?,ICD-9-CM,WE HAVE SPECIFIC ICD-9-CM CODES FOR OSTEOPOROSIS, OSTEOMYELITIS AND OSTEORADIONECROSIS SO WHY NOT USE THESE CODES FOR BP RELATED ASEPTIC OSTEONECROSIS OF THE JAW OR BRON JAW?,NEED FOR A

13、SPECIFIC CODE,REPORTING INCIDENCE OF OCCURRENCE AND TRACKING RESEARCH EVALUATION & MANAGEMENT AND SURGICAL PROCEDURES OF MAXILLA AND MANDIBLE LINKED TO A SPECIFIC VS NON-SPECIFIC ICD-9CM CODE,BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW (ONJ),FIRST RECOGNIZED IN 2003 AS A COMPLICATION OF BISPHOSP

14、HONATE THERAPY HIGHER FREQUENCY IN THE MANDIBLE (63%) THAN IN THE MAXILLA (38%) ETIOLOGY IS UNCLEAR AND IS THE SUBJECT OF CURRENT RESEARCH AND INVESTIGATION,BRONJ,CAN BE RELATED TO DENTAL TREATMENT CAN BE RELATED TO DENTAL PATHOLOGY CAN BE SPONTANEOUS WITH DENTAL ETIOLOGY CAN BE RELATED TO DENTURE I

15、RRITATION OR WEAR CAN BE UNRELATED TO ANY OF THE ABOVE CAN BE RELATED TO LOCAL TRAUMA CAN BE UNKNOWN IN ETIOLOGY,PROPOSED INDUCTION MECHANISMS,INHIBITION OF OSTEOCLAST ACTIVITY REDUCES BONE TURNOVER REDUCING REMODELING DECREASED NEW BONE FORMATION ETIOLOGY IS UNKNOWN BUT IS LIKELY MULTIFACTORIAL,BRO

16、NJ,TRUE INCIDENCE IS DIFFICULT TO ESTIMATE DEPENDING ON RECENT RETROSPECTIVE REPORTS COULD BE 1%-9% OF CANCER PATIENTS RECEIVING BISPHOSPHONATES SEEN IN CANCER PATIENTS WITH MULTIPLE ANTINEOPLASTIC MEDICATIONS AS WELL AS BISPHOSPHONATES MULTIPLE MYELOMA, BREAST CANCER AND PROSTATE CANCER ARE THE PRI

17、MARY NEOPLASMS AFFECTED AND WHAT ABOUT OSTEOPOROSIS PATIENTS TREATED WITH BPs?,ONJ,MULTIPLE PAPERS RELATING BPs WITH ONJ SINCE 2003 RELATED TO METHOD OF ADMINISTRATION OF BPs: IV VS PO RELATED TO THE DURATION OF ADMINISTRATION VERY SERIOUS SEQUELAE WHEN ONJ DEVELOPS,BPs Mechanism of action,1) Tissue

18、 levela. reduction of bone turnover2) Cellular levela. inhibition of osteoclastic activity on thebone surface (Rodan et al., Strewler)b. inhibition of osteoclast recruitment on thebone surface (Rodan et al., Vitte et al.)c. osteoclast apoptosis (Hughes et al., Rogers et al.),BPs Mechanism of action,

19、3) Molecular levelInterferes with osteoclast intercellular biochemical pathways Inhibition of farnesyl diphosphate synthase Metabolized to toxic analogue of ATP (non-nitrogen containing BPs),Strewler GJ. N Engl J Med 2004;350:1174,Bisphosphonates,Pharmacologic action:- Inhibition of bone resorption

20、Pharmacokinetics:- Distribution: Rapid accumulation in sites of increased bone deposition/resorption, low plasma levels, life of “years”- Metabolism: Not metabolized (nitrogen containing)- Excretion: Renal,Staging,Stage 1 Characterized by exposed bone that is asymptomatic with no evidence of signifi

21、cant soft tissue infection,Staging,Stage 2Exposed bone associated with pain, soft tissue and/or bone infection,Staging,Stage 3 Pathologic fracture Exposed bone associated with soft tissue infection or pain that is not manageable with antibiotics due to the large volume of necrotic bone.,Staging,Stag

22、e 3 Pathologic fracture Exposed bone associated with soft tissue infection or pain that is not manageable with antibiotics due to the large volume of necrotic bone.,A 40 yo with female with a diagnosis of breast cancer and Zometa therapy (6 months) presents with pain, exposed and infected maxillary

23、bone following extraction,Relative Potency,Etidronate (Didronel) 1 Tiludronate (Skelide) 10 Pamidronate (Aredia) 100 Alendronate (Fosamax) 1,000 Risedronate (Actonel) 10,000 Ibandronate (Boniva) 10,000 Zolendronic acid (Zometa) 100,000,PROPOSAL,NEW DIAGNOSTIC ICD-9CM CODE FOR THE ASEPTIC NECROSIS OF

24、 BONE IN THE JAWS: NEW CODE: 733.45 JAW (MAXILLA AND MANDIBLE) AND APPROPRIATE NEW E CODES TO IDENTIFY THE SPECIFIC ROUTE OF ADMINISTRATION E933.6 ORAL BISPHOSPHONATES AND E933.7 INTRAVENOUS BISPHOSPHONATES,Combinations,Use E933.1 antineoplastic & immunosuppressive drugs and May also need to Code for the primary neoplasm (most common ones are prostate, breast and myeloma),