A120 Osteonecrosis of the Jaw in Multiple Myeloma Patients: Risk Factors of Early ONJ, Decreased Impact After 2005

Purpose To describe the clinical, radiologic, and pathologic features and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients. Patients and Methods A retrospective review of 90 MM patients who had dental assessments, including 22 patients with ONJ. There were 62 men; the median age was 61 years in ONJ patients and 58 years among the rest. Prior MM therapy included thalidomide (n = 67) and stem-cell transplantation (n = 72). Bisphosphonate therapy included zoledronate (n = 34) or pamidronate (n = 17) and pamidronate followed by zoledronate (n = 33). Twenty-seven patients had recent dental extraction, including 12 patients in the ONJ group. Median time from MM diagnosis to ONJ was 8.4 years for the whole group. Results Patients usually presented with pain. ONJ occurred posterior to the cuspids (n = 20) mostly in the mandible. Debridement and sequestrectomy with primary closure were performed in 14 patients; of these, four patients had major infections and four patients had recurrent ONJ. Bone histology revealed necrosis and osteomyelitis. Microbiology showed actinomycetes (n = 7) and mixed bacteria (n = 9). More than a third of ONJ patients also suffered from long bone fractures (n = 4) and/or avascular necrosis of the hip (n = 4). The variables predictive of developing ONJ were dental extraction (P = .009), treatment with pamidronate/zoledronate (P = .009), longer follow-up time (P = .03), and older age at diagnosis of MM (P = .006). Conclusion ONJ appears to be time-dependent with higher risk after long-term use of bisphosphonates in older MM patients often after dental extractions. No satisfactory therapy is currently available. Trials addressing the benefits/risks of continuing bisphosphonate therapy are needed.

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Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: a single-centre experience in 303 patients

British Journal of Haematology ◽

10.1111/j.1365-2141.2006.06230.x ◽

2006 ◽

Vol 134 (6) ◽

pp. 620-623 ◽

Cited By ~ 186

Author(s):

Kostas Zervas ◽

Evgenia Verrou ◽

Zisis Teleioudis ◽

Konstantinos Vahtsevanos ◽

Anastasia Banti ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Osteonecrosis Of The Jaw ◽

Single Centre ◽

Single Centre Experience ◽

Incidence Risk

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Osteonecrosis of the Jaw in Multiple Myeloma Patients: Incidence and Characteristics in Korean Patients.

Blood ◽

10.1182/blood.v114.22.4956.4956 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4956-4956 ◽

Cited By ~ 1

Author(s):

Hyo Jung Kim ◽

Hyeok Shim ◽

Eunkyung Park ◽

Min Kyoung Kim ◽

Seok Jin Kim ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Retrospective Study ◽

Conflicts Of Interest ◽

Previous History ◽

Clinical Manifestations ◽

Osteonecrosis Of The Jaw ◽

Korean Patients ◽

Dental Procedures ◽

Exposed Bone

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.

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Novel risk factors for osteonecrosis of the jaw in multiple myeloma: A RADAR report.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6623 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6623-6623

Author(s):

Jaimee S Holbrook ◽

Steven M Trifilio ◽

June M. Mckoy ◽

Seema Singhal ◽

Alfred Rademaker ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Multiple Myeloma ◽

Stem Cell ◽

Kidney Disease ◽

Stem Cell Transplant ◽

Osteonecrosis Of The Jaw ◽

Cell Transplant ◽

Rank Analysis ◽

Novel Risk Factors

6623 Background: Osteonecrosis of the jaw (ONJ) was identified in 2001 and is commonly seen in multiple myeloma (MM). The objective of this study is to evaluate novel risk factors in MM cases from a retrospective database. We hypothesized that ONJ may be related to stem cell transplant, chronic kidney disease and active smoking. Methods: We conducted a retrospective case-control study of 231 MM cases (from January 1, 1998 to September 30, 2010) identified from the electronic data warehouse (EDW) at Northwestern University (NU). The EDW is cross-institutional and integrates clinical data across NU. It comprises more than 2.3TB of data on roughly 2 million patients. The search terms used were: bisphosphonates, pamidronate, zoledronic acid, multiple myeloma, plasma cell disorders, osteonecrosis of the jaw, jaw abscess, dental abscess, among other terms described in literature. Data was abstracted onto a standardized form by 2 trained abstractors and validated by a clinician reviewer (BJE). Known and hypothesized new risk factors were abstracted, including duration of myeloma, treatment used, duration of bisphosphonate use, renal function indices, chemotherapy (vincristine, doxorubicin (A), dexamethasone (D) , thalidomide (T), cisplatin (P), cyclophosphamide (C), etoposide (E), novel agents [bevacizumab, sorafenib, angiostatin]) GCSF, smoking, and MM clinical stage. Analyses included T test, Wilcoxon, and log rank analysis. Results: ONJ occurring after MM diagnosis was identified in 33 cases out of a total of 233 cases of MM. ZOL, VAD, DT-PACE, and diabetes were more common in ONJ cases. Log rank analysis identified 2 risk factors for ONJ, the use of DT-PACE (p= 0.003), and complete and partial remission (p=0.007). Stem cell transplant and chronic kidney disease were not associated with ONJ. Conclusions: We identified novel risk factors for ONJ in MM, mainly partial or complete remission and use of DT-PACE. These results should prompt clinicians to heightened awareness and increased surveillance for the symptoms of ONJ for patients treated with DT-PACE.

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Incidence and Risk Factors of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients Having Undergone Autologous Stem Cell Transplantation

Onkologie ◽

10.1159/000343950 ◽

2012 ◽

Vol 35 (11) ◽

pp. 658-664 ◽

Cited By ~ 24

Author(s):

Cornelia Then ◽

Natalie Hörauf ◽

Sven Otto ◽

Christoph Pautke ◽

Emmo von Tresckow ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Osteonecrosis Of The Jaw

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Osteonecrosis of the Jaw in Multiple Myeloma Patients (the IFM Registry).

Blood ◽

10.1182/blood.v110.11.4809.4809 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4809-4809

Author(s):

Jean Gabriel Fuzibet ◽

Marie Hélène Viellard ◽

Benoit B.R. Rossignol ◽

Chantal C.D. Doyen ◽

Cyril Hulin ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Risk Factor ◽

Osteonecrosis Of The Jaw ◽

Dental Extraction ◽

Purulent Discharge ◽

Adverse Side Effect ◽

Dental Infection ◽

Exposed Bone ◽

Extensive Surgery

Abstract PURPOSE: to describe the incidence, characteristics and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM). PATIENTS AND METHODS : retrospective review of 51 ONJ collected from the IFM centers. For MM, age at diagnosis, isotype, DS staging, nature of chemotherapy and number of Stem-Cell Transplantation were the same that expected. RESULTS: ONJ occurred predominantly in the mandible (70%). The median time of exposure to biphosphonates (BP) was 45 months (4 to 144 months). BP therapy included: zoledronate (85%), pamidronate (10%), clodronate (5%), all of the patients have received intravenous BP before, two patients have no BP at the time of diagnosis of ONJ. RISK FACTORS: dental extraction (59%) other dental care (5%), dental infection (24%), others (30%), no risk factor (10%). SYMPTOMS: pain (92%), purulent discharge (37%), presence of exposed bone (60%), fracture (2%). MANAGEMENT: BP discontinuation (84%), medical treatment (86%), removal of sequestra (51%), extensive surgery (20%). EVOLUTION: improvement (55%), chronical symptoms (70%). INCIDENCE: we have not the number of exposed patients but: 46 centers/73 reported no ONJ.The first report was march 2001. In the same period, 1695 patients where included in IFM trials and only 16 ONJ where observed. Year of diagnosis: before 2004: 5 cases; 2004: 11 cases; 2005:26 cases; 2006: 7 cases; 2007(6 months): 2cases. CONCLUSION: ONJ is an adverse side effect of amino BP therapy (zoledronate>pamidronate), is time dependant and often after dental extraction. Preventive recommandations applied in 2005 can explain the decreasing incidence of ONJ in our study.

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Safety and efficacy of bone-modifying agents among multiple myeloma patients: A retrospective cohort study

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155221996039 ◽

2021 ◽

pp. 107815522199603

Author(s):

Christina Billias ◽

Megan Langer ◽

Sorana Ursu ◽

Rebecca Schorr

Keyword(s):

Multiple Myeloma ◽

Cohort Study ◽

Zoledronic Acid ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Osteonecrosis Of The Jaw ◽

Safety And Efficacy ◽

Modifying Agent ◽

Skeletal Related Events ◽

Agent Group

Objective To determine the incidence of skeletal-related events among multiple myeloma patients who received chemotherapy without a bone-modifying agent (zoledronic acid and denosumab) versus those who received chemotherapy with a bone-modifying agent. The secondary objective was to determine the incidence of skeletal-related events in patients without any prior history of skeletal-related events and who were treated with zoledronic acid every four weeks versus those who received zoledronic acid at an extended interval of every twelve weeks. Additional secondary objectives included the incidence of nephrotoxicity, hypocalcemia and osteonecrosis of the jaw in all patients. Methods This institutional review board-approved, retrospective cohort study included patients 18 to 89 years old with a diagnosis of multiple myeloma, who were being treated with chemotherapy between July 1, 2016 and October 31, 2019. Safety and efficacy were assessed through analysis of pertinent data collected: patient demographics, baseline skeletal-related events, development of new skeletal-related events, number and type of bone-modifying agent doses administered, and drug-related toxicities such as nephrotoxicity, hypocalcemia, and osteonecrosis of the jaw. Results A total of 73 patients were included. New skeletal-related events occurred in 12 patients (27%) in the chemotherapy without a bone-modifying agent group and in 5 patients (17%) in the chemotherapy with a bone-modifying agent group (OR = 0.56, 95% CI [0.172–1.8]; P = 0.32). The incidence of skeletal-related events was similar among patients receiving zoledronic acid every four weeks versus every twelve weeks in patients without a prior skeletal-related event (N = 0 vs. N = 2 respectively; P = 0.47). There were no statistically significant differences observed in each of the three secondary safety endpoints: incidence of hypocalcemia, nephrotoxicity and osteonecrosis of the jaw. Conclusion Multiple myeloma patients receiving chemotherapy without a bone-modifying agent had higher rates of skeletal-related events compared to those being treated with chemotherapy and a bonemodifying agent. Our results highlight the benefit of utilizing bonemodifying agents for the prevention of skeletal-related events in all multiple myeloma patients being treated with chemotherapy.

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