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Case reports of BRONJ

Case reports of BRONJ. 指導老師 : 王文岑醫師暨口腔病理科全體醫師 實習 E 組 Intern 廖昱豪 張庭維 謝旻芸 黃于芳 曾家展. Case 1. General data. Name : 葉 x 英 Gender: Female Age : 76 y/o Native : 屏東縣 Marriage status : Married Occupation : 無. Chief Complaints. R’t submandibular swelling for 2 months.

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Case reports of BRONJ

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  1. Case reports of BRONJ 指導老師: 王文岑醫師暨口腔病理科全體醫師 實習E組 Intern 廖昱豪 張庭維 謝旻芸 黃于芳 曾家展

  2. Case 1 General data • Name :葉x英 • Gender: Female • Age : 76 y/o • Native : 屏東縣 • Marriage status : Married • Occupation : 無

  3. Chief Complaints R’t submandibular swelling for 2 months

  4. Present Illness • 97.12.11 • This 74 y/o female was suffered from the above episode, at first she went to LDC , the dentist suggest ed her to come to our OPD for further examination. She took Fosamax. • 2 polyps at right edentulous ridge, local pus (+) • Right submandibular swelling about 5*7cm

  5. Past History Past Medical History • Hypertension(+) DM(-) denied other systemic illness • Hospitalized:置換人工膝關節 • osteoporosis • drug or food allergy: penicillin • Medication: drug for hypertension control 膝關節藥物 Forsamax (alendronate(口服) 次/週 for 4~5 yrs )

  6. Past Dental History Extraction ,C&B,OD,RCT • Attitude to Dental Tx：Fair • Oral Habits Alcohol : (-) Betel quid : (-) Cigarette (-)

  7. 3x3 cm • Mixed RL with RO, irregular shape bony destruction

  8. Differential Diagnosis ●Tumor • Benign (X) • Malignancy osteosacoma odontogenic malignancy tumor ●Infection Osteomylities

  9. Clinical impression • Bisphosphonate- related osteonecrosis of jaw (BRONJ)

  10. Treatment course • 97.12.11 (first visit) refer from LDC I&D anaerobic culture, aerobic culture Rx: amoxicillin/ panadol / suwell • 97.12.18 pus culture report Clostridium bifermentans →metronidazole(+) Ampicillin (+) Clindamycin (+)

  11. 97.12.12~97.12.31 N/S irrigation Antibiotic • 98.1.7 arrange OP • 98.1.15 OP: sequestrectomy +saucerization

  12. 98.3.4

  13. 98.5.6 Remove sequestrum (in OPD)

  14. 98.9.16 F/U

  15. General data Case 2 • Name : 涂沈秀月 • Gender: Female • Age : 51 y/o • Native : Kaohsiung • Marriage status : Married • First Visit : 97/12/18

  16. Chief Complaints • Ask for oral examination for dental care after 骨針 application • Bad smell from wound of extraction for more than 1 year.

  17. Present Illness • 97/12/18 This 49 y/o female has received Zometa IV monthly for bone metastasis for about 3 years. And the nurse of cancer center suggested her to visit our OPD for oral examination. She stated she had extraction experience of teeth 15 and 16 more than 1 year ago in LDC.

  18. Past History • Past Medical History • Breast carcinoma with bone metastasis (T1N2M1)s/p operation , systemical chemotherapy and radiotherapy. • Serous microcystic adenoma over pancreatic tail s/p partial pancreatectomy • Otitis media s/p eardrum reconstraction • Tonsil excision

  19. Past Dental History • Extraction, C&B fabrication, OD, scaling • Attitude to Dental Tx：Fair • Oral Habits Related to Malignancy: • Alcohol : (-) • Betel quid : (-) • Cigarette : (-)

  20. Oral Examination • A fistula was found on edentulous ridge of teeth 15 &16, tracing with GP to take a periapical film. • Missing: • 15,16,17,18,27,28,37,38,45,46,48 • Caries : 13(D),14(M),34(B) • Metal crown : 22,23,24,25,26,35,36,44xx47 • PFM crown: 42

  21. Panorex findings There is an ill-defined bony destruction area about 2x2cm in diameter over edentulous ridge of teeth 15 and 16 .

  22. Differential diagnosis • Bisphosphonate related osteomyelitis over R’t post. Maxilla • Breast carcinoma with bone metastasis of jaw • Osteoradionecrosis of the jaw (ORN) Clinical Impression : Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)

  23. Treatment Plan • Antibiotic therapy • Local debridement • Advanced surgical management

  24. 98.8.13

  25. Cases review of BRONJ (KMUH)

  26. Cases review Patient source: 14 BRONJ patients in KMUH dental dept. Methods: chart review 1.bisphosponate(BP) usage 2.radiographic evaluation 3.systemic condition 4.oral hygiene and dental condition

  27. General data Sex: Male : Female = 0:14 (female 100%) Age: 21-50 y/o: 1 (7.1%) 51-60 y/o: 2 (14.2%) 61-70 y/o: 3 (21.3%) 71-80 y/o: 6 (42.6%) 81-90 y/o: 2 (14.2%) Range: 42-82, average : 69 y/o Reason for BP usage: Breast ca (BC) with bone meta or prevention: 6(42.8%), Osteoporosis: 8(57.2%) DM: 5 (35.5 %)

  28. Used form of BP • BC • O • A :8 (oral) • P: pamidronate

  29. 11-30m: 3 31-50m: 6 51-70m: 1 71-90m: 2 101-110m: 1 Minimum: 13m (A/oral) Maximum:103m (A/oral) Average: 47m Side effect: not obvious Using time of BP(months)

  30. Bony exposure:12/14(85.7%) Lesion Numbers Lesion characteristics • Locations

  31. Clinical characteristics Symptoms and signs

  32. Clinical characteristics • Radiographic features • Lesion size • Maxium: 5*3 cm • Minimum: 1*1 cm

  33. Special events ONJ staging

  34. Event~ BRONJ • 使用bisphosphonate 到發病時間 Minima: 12 Maxima: 94 Average: 44.8

  35. Clincal procedures & treatments • Biopsy: 7/14 (50%) • Bacterial culture:6/14 (42.9%) Clostridium bifermentans staphylococus epidermidis propionibacterium species • Antibiotic: 14/14 (100%) amoxicillin, clindamycin, metronidazole, clindamycin, • Local irrigation and debridement: 12/14 (85.7%) • Operation (in OR) : 6/14 (42.9%) • HBO : 4/14 (28.6%)

  36. Periodontitis: 12/14 (85.7%) • 感染性骨髓炎:

  37. 更年期過後的婦女因為罹患乳癌和骨質疏鬆症的機率增加，用藥機率增加，所以為高危險群更年期過後的婦女因為罹患乳癌和骨質疏鬆症的機率增加，用藥機率增加，所以為高危險群 藥物本身副作用不明顯，所以使用普遍 11/14 (78.6%)的病人是因為拔牙傷口不癒合，且大多數病灶部位都在下顎後牙區 病患大多在服藥後1~5年內發病，平均44.8m 所有來診的患者皆有疼痛(100%)的情況，其次為化膿(92.9%) ，可見一般民眾會因為疼痛尋求解決，或是化膿意識到嚴重性求診 conclusion

  38. Discussion

  39. INDICATIONS AND BENEFITS OF BISPHOSPHONATE As a result, bone turnover becomes profoundly suppressed, and over time the bone shows little physiologic remodeling. • Bps. have high affinity for hydroxyapatite , remaining unmetabolized for long periods of time. • During bone remodeling, the drug is taken up by osteoblast and internalized in the cell cytoplasm. • Reducing recruitment and proliferation of osteoclast precursors and inducing osteoclast apoptosis. • Bps. also have antiangiogenic properties and may be directly tumoricidal.

  40. INDICATIONS AND BENEFITS OF BISPHOSPHONATE THERAPY J Oral Maxillofac Surg 67:2-12, 2009, Suppl • IV Bisphosphonates cancer-related conditions 1.hypercalcemia of malignancy 2.bone metastases (breast cancer, prostate cancer , lung cancer) 3.lytic lesions of multiple myeloma • Pamidronate(Aredia), Zoledronic acid(Zometa), Zoledronate(Reclast), Ibandronate(Boniva)

  41. J Oral Maxillofac Surg 67:2-12, 2009, Suppl • Oral Bisphosphonates • most prevalent and common indication  osteoporosis • Paget’s disease of bone and osteogenesis imperfecta of childhood. • Off-label uses Numerous other conditions where a decrease in bone remodeling by bisphosphonates might aid in disease management: • giant cell lesions of the jaw • pediatric osteogenesis imperfecta • fibrous dysplasia • Gaucher’s disease

  42. Common bisphosphonates

  43. Relative Potency *Relative to etidronate (a non-nitrogen-containing bisphosphonate with relative potency of 1). 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

  44. BRONJ Case Definition J Oral Maxillofac Surg 67:2-12, 2009, Suppl • Patients may be considered to have BRONJ 1. Current or previous treatment with a bisphosphonate. 2. Exposed bone in the maxillofacial region that has persisted for more than 8 weeks. 3. No history of radiation therapy to the jaws

  45. Incidence of BRONJ Independent epidemiological efforts from clinicians and the International Myeloma Foundation reported incidence estimates between 5% ~ 10%. J Oral Maxillofac Surg 67:2-12, 2009, Suppl • IV BISPHOSPHONATES • 0.8% to 12% • ORAL BISPHOSPHONATES • 0.7/100,000 person-years of exposure(Merck)underreporting. • Surveillance data from Australia (patients treated weekly with alendronate ) 0.01% to 0.04% • 13,000 Kaiser-Permanente members( long-term oral bps) 0.06% • IV>>oral.

  46. RISK FACTORS J Oral Maxillofac Surg 67:2-12, 2009, Suppl 1. Drug-related risk factors A. Bisphosphonate potency zoledronate (Zometa)> pamidronate(Aredia)> oral bps. B. Duration of therapy 2. Local risk factors A. Dentoalveolar surgery: 5-~21-fold increased risk in IV Bps. treated cancer patients. B. Local anatomy : Mandible : Maxilla=2:1 (Thin mucosa overlying bony prominences such as tori , bony exostoses, and the mylohyoid ridge) C. Concomitant oral disease: history of inflammatory dental disease are at a 7-fold increased risk.

  47. J Oral Maxillofac Surg 67:2-12, 2009, Suppl 3. Demographic and systemic factors A. increasing age ; whites. B. systemic factor (renal dialysis, low hemoglobin, obesity, and diabetes) C. chemotherapeutic agents (cyclophosphamide, erythropoietin, and steroids) D. tobacco users, alcohol exposure(X) …Wessel et al 4. Genetic factors single nucleotide polymorphisms, in the cytochrome P450-2C gene [CYP2C8] ……… Sarasquete et al

  48. Staging of BRONJ Clinical findings: 1. Loosening of teeth not explained 2. Fistula not associated with pulpal necrosis Radiographic findings: 1. Persistence of unremodeled bone in sockets 2. Thickening/obscuring of periodontal ligament 3. Inferior alveolar canal narrowing • Patient at risk : no apparent necrotic bone in asymptomatic patients who have been treated with IV or oral Bps. • Stage 0 :no clinical evidence of necrotic bone, present with nonspecific symptoms or findings, include Symptoms: 1. Odontalgia not by an odontogenic cause 2. Dull, aching bone pain in the body of the mandible 3. Sinus pain 4. Altered neurosensory function

  49. Stage1 : exposed and necrotic bone in patients who are asymptomatic and have no evidence of infection.

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