Osteonecrosis of the Jaw in Multiple Myeloma Patients: Incidence and Characteristics in Korean Patients.
Authors: Kim Hyo Jung , Shim Hyeok , Park Eunkyung , Kim Min Kyoung , Kim Seok Jin , Park Joon Seong , Won Jong-Ho , Min Chang-Ki , Lee Jae Hoon ,   Korean Multiple Myeloma Working Party, (KMMWP)
Published: October 2019

Abstract
Abstract 4956

Introduction
Osteonecrosis of the Jaw (ONJ) is a potentially serious complication of bisphosphonate (BP) therapy in multiple myeloma (MM). Despite of current update about bisphosphonate related ONJ (BRONJ), only a few Asian BRONJ cases were reported and incidence of BRONJ in Asian MM patients has not yet been definitively estimated. The purpose of this study was to determine incidence and characteristics of BRONJ in Korean MM patients who were receiving BP therapy.

Patients and Methods
We invited 9 hospitals of Korean Multiple Myeloma Working Group (KMMWP) to participate in a retrospective multicenter study on BRONJ in MM patients. To defined BRONJ incidence, we reviewed the data from 130 MM patients treated with BP in one hospital. We also reviewed the medical records of MM patients with BRONJ treated in 9 hospitals to know the patterns of disease. We analyzed patient and disease characteristics, type and number of BP infusions, previous history of dental procedures, locations of osteonecrosis, clinical symptoms, treatment and outcome. ONJ was defined as clinical evidence of exposed bone in the jaw, which has been present for more than 8 weeks.

Results
Nine of 130 MM patients (6.9%) treated with BP developed BRONJ in the hospital. Twenty-two patients with MM developed BRONJ after a median number of 17 BP infusions (range 6 - 50) in all 9 hospitals. None of the patients had been irradiated to the jaw. There were 14 male and 8 female patients. The median age was 62 years (range 46 – 75). Median time from MM diagnosis to BRONJ was 2.8 years (range 0.6 – 15.6). The MM isotype was IgG in 9, IgA in 8, IgM in 1, light chain in 3 and non-secretory myeloma in 1 patient. BP therapy included zoledronate (n = 2) or pamidronate (n = 4) and both drugs as sequential treatment (n = 16). Fifteen patients had recent problems in oral cavity (72.7%) and 14 had prior dental procedures (63.6%). The mandible was involved in 14 patients (63.6%), the maxilla in 7 (31.8%), and both the maxilla and mandible in 1 (4.5%). Patients usually presented with pain and soft tissue swelling. ONJ staging (Khan et al. Canadian consensus practice guidelines of Bisphosphonate associated ONJ. J Rheumatol 2008;35:1391-7) was used to define the severity, there were 5 patients in stage I, 14 in stage II and 1 in stage III. Because of the limitation of retrospective study, the stage of 2 patients could not be confirmed. Management of these established cases were discontinuation of BP and medical treatment including antibiotics and pain killer. Surgical debridement of necrotic bone was performed in 12 patients. From onset of exposed bone in jaw, patients were followed for median 11 months (range 4.2 - 42). Wounds of 10 patients were healed at median 175 days (range 60 – 404) after bone exposure. In 8 patients, lesions had persisted over 154 days (range 66 – 425). Evaluation was impossible for 4 patients due to loss of follow up. Four patients were dead because of disease progression (n = 3) or concomitant infection. BRONJ was healed in 2 of them.

Conclusions
To the best of our knowledge, this is the largest retrospective study ever reported about BRONJ in Asian MM patients. The incidence of BRONJ in Korean MM patients was 6.9% and this is similar with data in western countries. Clinical manifestations and outcome of BRONJ in Korean patients were not different from previously reported data, but no risk factors could be definitively identified with our retrospective analysis. In the name of KMMWP, prospective trials are ongoing to define incidence and risk factors of BRONJ in Korean MM patients.

Disclosures
No relevant conflicts of interest to declare.