3/13/2014. BRONJ Bisphosphonate Related Osteonecrosis of the Jaws. Bisphosphonates, Surgery, and Oral Health

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1 BRONJ Bisphosphonate Related Osteonecrosis of the Jaws Bisphosphonates, Surgery, and Oral Health Mark Engelstad DDS, MD, MHI Associate Professor Oral and Maxillofacial Surgery Medical Informatics and Clinical Epidemiology Sean Benson DDS Assistant Professor General Practice Residency Content Modified. Original Author = David Basi DDS, PhD 1

2 Case presentation Learning Objectives Definitions Discuss indications and routes of current bisphosphonate therapies. Describe what risk factors influence risk assessment. Determine relative risk as it relates to bisphosphonate therapy and clinical dentistry Treatment plan or referral decisions based on risk assessment Identify signs and symptoms of ONJ Inform patients of risks and benefits of treatment options as they relate to bisphosphonate therapy. ONJ: OsteoNecrosis of the Jaws BRONJ: BisPhosphonate related ARONJ: Anti-Resorptive Development of Bisphosphonates Were known to chemists since the 1850 s Early uses were industrial, mainly for corrosion prevention Bisphosphonate Uses Sodium pyrophosphate is a tartar control agent: remove calcium and magnesium from saliva prevents them from being deposited on teeth 2

3 Pharmacology Of Bisphosphonates Pyrophosphate analogs R 1 R 1 : influences chemical properties and pharmacokinetics Bisphosphonate Structures Alendronate (Fosamax) O - Zoledronic Acid (Zometa/ Reclast) O - C R 2 R 2 : determines chemical properties, mode of action and strength (potency) C C N N N Bisphosphonates Mechanism of Action Mevalonate Pathway Santini D et al. (2006) Mechanisms of Disease: preclinical reports of antineoplastic synergistic action of bisphosphonates Nat Clin Pract Oncol 3: doi: /ncponc0520 Bisphosphonate Mechanism of Action: The main cell target = Osteoclast Pharmacology of Bisphosphonates Action = Inhibition of bone resorption Endosome Anti-resorptive (bone) Anti-angiogenic Anti-tumorigenic Dunstan et al, Nature Clin Practice, 4:42,

4 Osteoclast IMPAIRED WOUND HEALING Scope of the problem Blood vessels gcarlson.com Osteoblast IV Bisphosphonates for cancer Metastatic Bone Disease (MBD): Skeletal related complications Treatment hypercalcemia of malignancy Prevention of Skeletal-Related Events (SRE) Reduction in bone pain for osteolytic lesions Skeletally Related Events (SRE) Skeletal related complications: Pathologic fractures Spinal cord compression Bone pain requiring palliative radiotherapy/ orthopedic surgery Pathologic fractures Spinal cord compression 4

5 Scope of Problem Estimated Number of Cases with Cancer and Metastatic Bone Disease in the U.S. in 2004 Kathy L. Schulman & Joseph Kohles. Economic Burden of Metastatic Bone Disease in the U.S. CANCER,109 (11), Skeletally Related Events (SRE) Tori Overall risk 48% - 68% who do not receive BP therapy Reduced risk with BP therapy Multiple Myeloma < 47% Breast < 47% Lung 39% Prostate 38% Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Long-term efficacy and safety of zoledronic acidecompared with pamidronate disodium in treatment of skeletal complications in patient with advanced multiple myeloma or breast carcinoma: a randomized, double blind, multicenter, comparative trial Cancer 2003; 98(8): Saad F, Gleason DM, Murray R, Tchekmedyyain S, Venner P, Lacombe L, et al. Long term efficacy of zoledronic acid for prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96(11): What s a met? Metastasis 5

6 Metastatic Bone Disease: The equates into millions of patients in the United States Myeloma Breast Prostate Lung The Result Reduced patient quality of life Economic Burden in the US (2004): Annual cost to treat cancer patient A proportion of patients will die as a direct consequence of their skeletal disease 5-year survival rate for women: with breast cancer = 96% with metastatic breast cancer = 21% Kathy L. Schulman & Joseph Kohles. Economic Burden of Metastatic Bone Disease in the U.S. CANCER,109 (11), Proportion of patients with skeletal-related events (mets) n=228 Pain: Zoledronic Acid v. Placebo n=228 P = J Clin Oncol May 20;23(15): Epub 2005 Feb 28. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebocontrolled trial. Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, Watanabe T, Goessl C, Ohashi Y, Takashima S. J Clin Oncol May 20;23(15): Epub 2005 Feb 28. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebocontrolled trial. Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, Watanabe T, Goessl C, Ohashi Y, Takashima S. 6

7 Bisphosphonate treatment is similarly beneficial with other cancers: Hypercalcemia of Malignancy Multiple myeloma Prostate Cancer Renal Cancer Lung cancer Abnormally high level of calcium in blood Normal range mg/dl Most common life-threating metabolic disorder caused by cancer Hypercalcemia of Malignancy Hypercalcemia of Malignancy Symptoms Nausea and vomiting Loss of appetite Excessive thirst Frequent urination Constipation Abdominal pain Muscle weakness Muscle and joint aches Confusion Lethargy and fatigue Etiology Osteolysis Factors secreted by cancer cells can increase calcium levels Immobility Dehydration Hypercalcemia of Malignancy Most common cancers where BPs are used to manage hypercalcemia Multiple myeloma 40%-50% Breast 20% Lung 20% Prostate - 10% Waller A, Caroline NL. Hypercalcemia. Handbook of Palliative Care in Cancer 2 nd ed. Boston, MA: Butterwirth-Heinemann;2006. p

8 Hypercalcemia and Metastasis what s the difference? Oral Bisphosphonate Therapy Osteoporosis Normal Bone Osteoporosis Progression without symptoms---until fracture In the US: A threat for an estimated 44 million People over 50 years of age 50% of women 25% of men Osteoporotic bone Low bone mass Disruption in skeletal microarchitecture America's Bone Health: The State of Osteoporosis and Low Bone Mass in our Nation. Washington, DC: National Osteoporosis Foundation; 2002 Vertebral Fracture Risk Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures n=2027 Alendronate treatment reduced vertebral fracture risk by 47% (P <.001) compared to placebo Summary of bisphosphonate use: A class of drugs use to primarily treat or treat the sequelae of many types of cancer and diseases of bone, including osteoporosis Scientifically proven to benefit patients : increased bone density Black DM, Cummings SR, Karpf DB, et al. Lancet. 1996;348:

9 Key concept: Route I.V. vs. P.O. The reason the patient is taking a bisphosphonate, and the potency is of greater importance in determining risk of ONJ than the route of medication. Risk Factors for p.o. tx osteoporosis Age > 65 Duration of Therapy > 2 years Pre-existing dental/periodontal disease Smoking DM Corticosteroids +/- Prosthesis IV Bisphosphonates for Osteoporosis are effective and associated with no increased risk of ONJ. Preventive strategy before the initiation of BP therapy Inform patient of risks and sequelae of osteonecrosis Dodson, T J Intravenous Bisphosphonate Therapy and Bisphosphomnate Related Osteonecrosis of the Jaws Oral Maxillofac Surg 67:44 52, 2009 Suppl 1 Risk Bisphosphonates for osteoporosis have a low risk of developing ONJ (0.10%) 1:952 Risk can be minimized but not eliminated There is no validated diagnostic technique is currently available to determine which patients are at increased risk Discussion of risk Oral hygiene, and regular care may be the optimal approach for lowering risk Discontinuing bisphosphonate therapy will not eliminate risk, and can have serious systemic health implications. Interdisciplinary discussion required Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142, Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142,

10 Perspective Risk Annual Deaths Lifetime risk Heart disease 652,486 1 in 5 Cancer 553,888 1 in 7 Stroke 150,074 1 in 24 Hospital infections 99,000 1 in 38 Flu 59,664 1 in 63 Car accidents 44,757 1 in 84 Suicide 31,484 1 in 119 Accidental poisoning 19,456 1 in 193 MRSA (resistant bact) 19,000 1 in 197 Falls 17,229 1 in 218 Drowning 3,306 1 in 1,134 Other Dental Related Risk Paresthesia after mandibular third molar removal 2.6% lingual 3.9% IAN Bataineh AB Sensory nerve impairment following mandibular third molar surgery, J Oral Maxillofac Surg 59: Sources: Unless otherwise noted, all accidental death information from National Safety Council. Disease death information from Centers for Disease Control and Prevention. Lifetime risk is calculated by dividing 2003 population (290,850,005) by the number of deaths, divided by 77.6, the life expectancy of a person born in Clinical Features Protracted bisphosphonate treatment is associated with Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ) Oral Cutaneous Fistula Location of BRON (%) Both Jaws Maxilla Mandible n=368 Sook-Bin Woo, DMD; John W. Hellstein, DDS, MS; and John R. Kalmar, DMD, PhD Ann Intern Med. 2006;144:

11 Acute infection Pain Mark Collen Sacramento, California Trapped In Hell Radiologic Features Osteolysis Increased radiopacity of the: a) Alveloar crest b) Lamina dura Sclerosis Widened PDL space Phal PM et al, Am J Neurorad (2007) 28:1139. Periosteal bone formation Role of plain films in the diagnosis and treatment of BRONJ Tooth extracted 18 months earlier Residual radiographic outline of extraction socket Findings are non-specific Not sensitive compared to other techniques Arce et al. Imaging Findings in Bisphosphonate-Related Osteonecrosis of Jaws. J Oral Maxillofac Surg 67:75-84, 2009, Suppl 1 Plain Film Courtesy of JQ Swift 11

12 CT Sequestrum Periosteal bone formation Courtesy of JQ Swift CT or Plain Radiography for BRONJ Diagnosis CT is superior compared to panoramic radiography in identifying all radiologic signs of BRONJ CT findings showed a consistent association with clinical severity MRI Can detect cancellous bone involvement which produced low signal Bone sequestrum was evident, which produced a well-defined dark signal area OPG for screening Silvio Diego Bianchi, et al. Computerized tomographic findings in bisphosphonate-associated osteonecrosis of the jaw in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:249-58) S Chiandussi, et al. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofacial Radiology (2006) 35, MRI Scintigraphy: 99Tcm-MDP Three-phase Bone Scan 99Tcm-MDP: Technitium 99 - Medronate In all cases, the bone scan was positive for the presence of bone lesions Abnormal localized activity in the jaws in comparison with the surrounding regions Luis García-Ferrer, et al. MRI of Mandibular Osteonecrosis Secondary to Bisphosphonates. AJR 2008;190: S Chiandussi, et al. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofacial Radiology (2006) 35,

13 Scintigraphy Limitations include low resolution Difficulty in differentiating between inflammation and/or metastasis and/or BRONJ BRONJ Radiography/ Imaging Synopsis OPG (Orthopantomogram) for initial screening CT scans to determine: The extent of the BRONJ To Plan surgical treatment What we really want to know is 1. Can we use clinical imaging to predict development of BRONJ 2. Detect BRONJ before clinical signs manifest Before Bisphosphonate Tx 33 months later 6 months later Felice S. O Ryan, et al. Intravenous Bisphosphonate-Related Osteonecrosis of the Jaw: Bone Scintigraphy as an Early Indicator. J Oral Maxillofac Surg 67: , Concerns H&E 20x BRONJ Histologic Features Scans cannot distinguish between inflammatory dental disease and ONJ More studies are needed Non-specific Necrotic bone 13

14 BRONJ Histologic Features Both BRONJ and ORN had a similar proportion of specimens associated with Actinomyces. BRONJ n= 8 ORN n=10 Different Bone Diagnoses Osteitis Osteomyelitis ONJ GMS20x Torsten Hansen, et al. Osteonecrosis of the jaws in patients treated with bisphosphonates histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med (2006) 35: Osteitis Osteomyelitis ORN ONJ 14

15 ONJ Microbiologic Features: Organisms similar to those seen in odontogenic infections and periodontal disease: Streptococcus spp, Fusobacterium Eikenella corrodens Bacteroides fragilis Enterobacteriaceae Klebsiellae Beta-haemolytic Streptococcus Group F Haemophilus influenzae BRONJ is a Diagnosis Of Exclusion Exposed bone of 8 weeks duration +/- pain +/- infection +/- cutaneous fistula Previous use of bisphosphonates WITHOUT history of radiation to head and neck Primary diagnosis associated with BRONJ (%): Osteoporosis Prostate CA 4 6 Other n=368 4 BRONJ Stage: 0 (range = 0-4) Stage 0: patients exposed to bisphosphonates and Breast CA 39 Multiple Myeloma 47 who present with non-specific jaws symptoms, such as pain without an identifiable source, or clinical and radiographic abnormalities. Sook-Bin Woo, DMD; John W. Hellstein, DDS, MS; and John R. Kalmar, DMD, PhD Ann Intern Med. 2006;144: Ruggiero et al, OOOOE 102:433, 2006 BRONJ Stage: 1 Stage 1: Exposed/necrotic bone in patients who are otherwise asymptomatic and have no evidence of infection BRONJ Stage: 2 Stage 2: Exposed/necrotic bone in patients with pain and clinical evidence of infection 15

16 BRONJ Stage: 3 Stage 3: Exposed/necrotic bone extending beyond the region of alveolus in patients with pain, infection, and with one of the following : BRONJ Stage: 3 In this OPG: Osteolysis Inferior Border Changes Pathologic Mandible Fracture? Mandibular inferior border osteolysis, maxillary sinus or zygoma Pathologic fracture Cutaneous fistula BRONJ estimated incidence: By Bisphosphonate Route of Administration: Intravenous 4% Oral = 1 of 952 = percent Lo JC, et al. Prevalence of osteonecrosis of the jaw in patients Woo et al, with Ann oral Intern bisphosphonate Med 144:753, 2006 exposure. Dunstan et al, Nature Clin Practice 4:42, 2007 J Oral Maxillofac Surg Feb;68(2): Mavrokokki et al, JOMS 65:415, 2007 J Oral Maxillofac Surg 67:2-12, 2009, Suppl 1 Bisphosphonate Route Of Administration Associated With BRON (%) Oral CONDOR study results: (a case-control study of BRONJ) NIDCR-funded practice based networks Quantified the impact of BP exposure on the risk of developing ONJ, relative to comparable control patients All the patients with ONJ identified from the practice based networks were recruited for the study. Intravenous More than 200 cases of ONJ -- January 2005 and January Risk Factors for Osteonecrosis of the Jaws : a Case-Control Study from the CONDOR Dental PBRN A. Barasch, J. Cunha-Cruz, F.A. Curro, P. Hujoel, A.H. Sung, D. Vena, A.E. Voinea-Griffin and the CONDOR Collaborative J DENT RES : 439 originally published online 11 February

17 Use of Bisphosphonates prior to BRONJ Oral: Odds Ratio = 9.76 I.V. & Oral: Odds Ratio = Duration: 0 2 years: Odds Ratio = years: Odds Ratio = 41.1 > 5 years: Odds Ratio = 38.2 Tooth Extraction: Odds Ratio = 7.1 Univariate analysis Multivariate analysis Relative potencies of Bisphosphonates: Etidronate (Didronel ) 1 Pamidronate (Aredia ) 100 Alendronate(Fosamax ) 500 Ibandronate (Boniva ) 1000 Risedronate (Actonel ) 2000 Zoledronate (Zometa ) Comparison of the route of administration Dental co-morbidities associated with BRON (%): IV Half life: 20 yrs-?? Bioavailability: >90% Onset of action: 24-48h Uptake in bone: 60-75% ORAL 10 yrs 1-2% Weeks 50% Percent of Patients n=119 Dunstan et al, Nature Clin Practice 4:42, 2007 Green, Oncologist 9:3, 2004 Marx RE, et al. JOMS 63:1567, 2005 Proximal Event: Periodontal surgery Existing Periodontal disease Tooth Extraction Apicoectomy Implant surgery Medical & Behavioral co-morbidities associated with BRONJ: Diabetes mellitus Corticosteroid Thalidomide treatment Smoking Alcohol use Marx RE, et al. JOMS 63:1567, 2005 n=119 17

18 Genetics may play a role in patient susceptibility to BRONJ development Evaluation of SNPs Single Nucleotide Polymorphisms Individual #1 A T C C G T A G G C Individual #2 A T T C G T A A G C BLOOD, VOLUME 112, NUMBER, 2008 Evaluation of with Multiple Myeloma 21 Patients with BRONJ 64 sex and aged matched without BRONJ Assessed 500,568 SNPs The most important Factors associated with BRONJ Length of treatment: >40 months Number of infusions: >35 infusions AAOMS Position Paper: Recommendations for patients with history of IV bisphosphonate use Patients With An Established Diagnosis Of BRONJ Areas of necrotic bone that are a constant source of soft tissue irritation should be removed or recontoured without exposure of additional bone. Loose segments of bony sequestrum should be removed without exposing uninvolved bone. American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws Approved by the Board of Trustees September 25,

19 Patients with an established diagnosis of BRONJ Months of Remission after HBO by Ongoing BP Treatment Avoid elective dentoalveolar surgical procedures If systemic conditions permit, consider discontinuation of the oral bisphosphonate Freiberger et al. HBO Treatment and Bisphosphonate-InducedOsteonecrosis of the Jaw. J Oral Maxillofac Surg Patients with BRONJ: Avoid elective invasive dental procedures Considered RCT, crown removal and allow tooth to exfoliate Removable appliance can be used to cover the exposed bone Well-fitting dentures can be worn Educate patients and make an informed decision together Patients about to initiate intravenous bisphosphonate treatment: Prior to initiation of bisphosphonate treatment complete extraoral and intraoral examination Optimal oral health should be achieved if possible All invasive dental procedures should be completed PRIOR to BP administration JOURNAL OF ONCOLOGY PRACTICE VOL. 2, ISSUE 1, Jan 2006 Practical Guidelines for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaw in Patients With Cancer. Salvatore Ruggiero, et al. JOURNAL OF ONCOLOGY PRACTICE VOL. 2, ISSUE 1, Jan 2006 Preventive strategy before the initiation of BP therapy Identify and treat existing infections, carious and other compromised teeth, and tissue injury or trauma. Stabilize or eliminate potential sites of infection. Preventive strategy before the initiation of BP therapy Conduct a prosthodontic evaluation if indicated. Perform oral prophylaxis if indicated. Time oral surgery to allow at least 2 weeks for healing before radiation therapy begins if possible. NIH Publication No NIH Publication No

20 Based on experience with OsteoRadioNecrosis: Delay bisphosphonate treatment (if it hasn t been started yet, and if systemic conditions permit), until the extraction site has mucosalized (14-21 days) or until there is adequate osseous healing Preventive strategy before initiation of BP therapy Key Concept Invasive treatment finished prior to initiation of BP therapy Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009; 20(1): Preventive strategy before the initiation of BP therapy Preventive strategy after initiation of BP therapy Prescribe an individualized oral hygiene regimen to minimize oral complications. NIH Publication No Aggressive recall consider 3-4 months Caries prevention Fluoride, xylitol, OHI Antimicrobial rinses Recognition/ mitigation of xerostomia Asymptomatic patients receiving I.V. bisphosphonates Procedures that cause osseous injury should be avoided. Non-restorable teeth Remove the crown Endodontic treatment of the remaining roots. Placement of dental implants should be avoided on a patients with potent I.V. dosing Periodontal therapy Non-surgical if possible 4-6 week recall Stop progression before extraction is indicated Surgical procedures are not contraindicated Goal of surgery access to root surfaces Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142,

21 Endodontic Therapy Root retention/exfoliation may be preferable to extraction in some cases Surgery is not contraindicated Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142, Restorative and Prosthodontics No evidence that malocclusion or masticatory forces increase risk of ONJ Routine services to prevent bone manipulation Proper fit and stability of prostheses to minimize tissue ulceration Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142, Zoledronic acid (Reclast) Administered once annually for the treatment of osteoporosis was approved by the FDA in August A single, large, prospective placebo-controlled study established its efficacy for this indication through 3 years of treatment. Two cases of osteonecrosis of the jaw were reported, one each in the treatment and control groups, suggesting a low risk of BRONJ with this treatment modality through 3 years Asymptomatic patients receiving oral bisphosphonate therapy: ** Elective dentoalveolar surgery does not appear to be contraindicated in this group. The risk of BRONJ is associated with increased duration (> three years) of bisphosphonate treatment J Oral Maxillofac Surg 67:2-12, 2009, Suppl 1 United States Food and Drug Administration. Center for DrugEvaluation and Research: Reclast label information. Available at: Oral bisphosphonate use for less than 3 years: No alteration or delay in the planned surgery is necessary. Implant considerations: Informed consent: Possible future implant failure Possible osteonecrosis of the jaws if the patient continues to take an oral bisphosphonate therapy 21

22 CTx testing Drug Holidays Biochemical serologic marker of bone turnover Insufficient evidence as a predictor of ONJ or aid in risk assessment Not usually feasible for cancer patients No current evidence that they minimize risk of ONJ without increasing SRE s Fleisher K, Welch G, Kottal S, Craig R, Saxena D, Glickman R Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus radiogrphic markers Oral Surg Oral Med Oral Path Oral Radio Endod 2010; 110: Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142, Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H, Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis, The Journal of the American Dental Association (November 1, 2011) 142, Oral Bisphosphonate use for less than 3 years with concomitant corticosteroid use: Oral bisphosphonate use for more than 3 years: If systemic conditions permit, consider discontinuation of the oral bisphosphonate (drug holiday) for at least three months prior to oral surgery If systemic conditions permit (consult prescribing physician), consider a drug holiday for at least three months prior to oral surgery The bisphosphonate should not be restarted until osseous healing has occurred The bisphosphonate should not be restarted until osseous healing has occurred The dentist should inform the patient taking oral bisphosphonates that: The risk of developing BRONJ is very low (0.1%) Management A comprehensive oral evaluation is recommended for all about to begin therapy with oral bisphosphonates Good oral hygiene along with regular dental care is the best way to lower risk of developing BRONJ Currently, no diagnostic techniques to identify those at risk of developing BRONJ 22

23 Treatment Stage 1 Use oral antimicrobial rinses, such as chlorhexidine 0.12%. No surgical treatment is indicated Clinical monitoring Treatment Stage 2 Use oral antimicrobial rinses Use systemic antibiotics If possible: Microbial cultures should also be analyzed for the presence of actinomyces species of bacteria. Antibiotic Treatment Patient Type Suggested Drug Oral Regimen Not allergic to PCN PCN VK 500 mg QID 14 days Allergic to PCN Clindamycin 300 mg TID 14 days Treatment Stage 3 These patients typically have pain and uncontrollable infections that impact quality of life. Anti-microbial mouth rinse: Chlorhexidine Surgical debridement/resection in combination with antibiotic therapy may offer long-term palliation with resolution of acute infection and pain. Restorative vs. Surgical treatment 73 y/o female Case study 1 History of breast cancer - invasive ductal carcinoma (stage IIIb) with liver, bone, and cutaneous metastases. Endodontic/restorative therapy as an alternative Palliative care management Bisphosphonate therapy Zoledronic acid for hypercalcemia CC broken left tooth, hurts constantly 3 case studies Pain level 5/10 23

24 Exam Radiograph Assessment and risk analysis Necrotic pulp with symptomatic periapical periodontitis High risk for ONJ ASA 4 Chronic pain management Endodontic Therapy Extract or Endodontic Therapy? Coronal amputation and restoration 65 y/o male Case 2 Prostate cancer (T3N1M1b) Bisphosphonate therapy for bone pain management Zoledronic acid History of SSC of buccal R mucosa treated with resection, chemo, and radiation No oral symptoms 24

25 Exam Radiograph Assessment and Risk Analysis Non symptomatic retained root tip Very high risk for ONJ Modified embrasure space to allow for access Patient demonstrated compliance to OH and recall schedule Informed consent/ clinical decision making documented in chart Root retention/ exfoliation Case 3 55 y/o male Prostate cancer (T3aN1M1b) Bisphosphonate Zoledronic Acid Symptomatic #14 with recurrent caries Periodontal disease Multiple co-morbidities Exam radiograph Periodontal probing 25

26 Stain to check for fracture ONJ appears Completion of endodontic therapy Stage 2 ONJ Stage 1 - ONJ Stage 1 - ONJ 26

27 Progress Progress Progress Progress Progress Progress 27

28 Progress Resolution 28