scholarly journals Bisphosphonate related osteonecrosis of the maxilla: A case report

2017 ◽  
Vol 74 (11) ◽  
pp. 1084-1088 ◽  
Author(s):  
Aleksandar Kiralj ◽  
Slobodan Loncarevic ◽  
Ivana Mijatov
Keyword(s):  
Case Report ◽  
Zoledronic Acid ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Bone Diseases ◽  
Acid Therapy ◽  
Treatment Stage ◽  
Upper Jaw ◽  
And Control ◽  
Intravenous Bisphosphonate

Introduction. Bisphosphonates are a group of medications which have an important role in the treatment of some bone diseases. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of intravenous bisphosphonate therapy. The mechanism of action by which they may cause osteonecrosis is questionable. BRONJ is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) and classified into four stages (0-3). Treatment of BRONJ depends on the stage of disease and includes conservative treatment (stage 0 and 1) and surgical treatment (surgical debridement in stage 2 and sequestrectomy in stage 3). Case report. We presented a patient who had breast cancer, with stage 3 of bisphosphonate-related osteonecrosis of the upper jaw after zoledronic acid therapy for diffuse metastasis of the vertebrae. Before the treatment with zoledronic acid the patient was treated by a dentist. The osteonecrosis of the upper jaw started a year and a half after the start of zoledronic acid therapy and after tooth 24 extraction. She was treated by an oral surgeon at the beginning according to the protocol of AAOMS. The patient was sent to a maxillofacial surgeon due to the disease progression, and after computed tomography (CT) examination resection of the upper jaw was done. Conclusion. BRONJ is a condition with the specific clinical presentation, and it can be very serious for the patient, therefore it is necessary to emphasize the importance of screening. The doctors in different specialties (oncologist, dentist, oral surgeon and maxillofacial surgeon) must cooperate and control the patients under treatment with bisphosphonates before the therapy starts, as well as during and after it, in order to prevent, recognize on time and treat properly this complication.

Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1113-1113
Author(s):  
V. Beck ◽  
E. Solomayer ◽  
M. Krimmel ◽  
C. Reinert ◽  
T. Fehm
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Gynecological Malignancies ◽  
Dental Procedures ◽  
The Mean ◽  
Number Of Treatment

1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.

scholarly journals Genetic Factors Related with Early Onset of Osteonecrosis of the Jaw in Patients with Multiple Myeloma Under Zoledronic Acid Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2115-2115
Author(s):  
Pelagia Melea ◽  
Tina Bagratuni ◽  
Evangelos Terpos ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Osteonecrosis Of The Jaw ◽  
Acid Therapy ◽  
Ppar Γ ◽  
Pathologic Fractures ◽  
Increased Risk ◽  
Significant Difference

Abstract Bisphosphonates are extensively used in the treatment of myeloma-related bone disease as they reduce pain and skeletal related events (SREs), such as pathologic fractures, need for radiation and surgery to the bone. One of the complications of prolonged therapy with bisphosphonates, especially of amino-bisphosphonates, such as zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). Recent studies have attempted to correlate specific genetic polymorphisms (SNPs) and ONJ. Such SNPs include cytochrome P4502C8 (CYP2C8; Sarasquete et al, Blood 2008) and peroxisome proliferator-activated receptor gamma (PPAR-γ; Di Martin et al, Br J Haematol 2011) that have been linked to increased risk of ONJ in two different series. The aim of this study was to investigate a possible association between SNPs in CYP2C8 and PPAR-γ and the risk of developing ONJ in a large number of MM patients who received ZA. We screened 36 patients who developed ONJ and 104 patients who did not develop ONJ for the SNPs of interest in PPAR-γ (rs1152003) and CYP2C8 (rs193495) genes by direct sequencing of peripheral blood derived DNA. All patients were treated with similar systemic anti-myeloma therapies during the same period of time, had received only ZA as antiresorptive therapy and were followed prospectively for the development of ONJ in a single center (Department of Clinical Therapeutics, University of Athens, Greece). The median follow up of the cohort was 72 months. The median number of ZA infusions was 27 (range: 4-107). Patients who developed ONJ had a median of 31 infusions versus 25 infusions for patients who did not develop ONJ. However, 31% of patients who developed ONJ had received less than 24 infusions of ZA. Median time to development of ONJ was 47 months (range: 7-182 months). The median relative dose intensity for ZA was 2.85 mg/month; it was 3.3 mg/month for those who developed ONJ and 2.7 mg/month for those who did not. An extraction preceded the development of ONJ in 60% of patients who developed ONJ, it was unprovoked in 20%, it was associated with trauma from dentures in another 15% and in 5% ONJ was preceded by a periodontal and/or periappical inflammation (abscess formation etc). There was no significant difference in frequency of the presence of SNPs in the two studied genes between patients with and without ONJ. However, there is a subset of patients who develop ONJ rather early, after the infusion of relatively few doses of ZA while others develop ONJ after protracted exposure to ZA. Since the most important factor associated with the development of ONJ after ZA therapy in patients with myeloma is the total dose of ZA, we analyzed separately patients who had less than 24 versus those who had at least 24 infusions of ZA. In patients with <24 infusions of ZA, the presence of SNPs in both PPAR-γ and CYP2C8 was associated with a significantly higher probability and a shorter time to development of ONJ. More specifically, the presence of SNPs in the PPAR-γ was associated with a significantly higher risk of development of ONJ with less than 24 ZA infusions (55% versus 16%, p=0.011) and at a significantly shorter time to development of ONJ (19 versus 69 months, p<0.001). The presence of SNPs in the CYP2C8 was associated with a higher risk of developing ONJ with less than 24 ZA infusions (29% versus 7%, p=0.07) and at a shorter time (44% versus 13% at 3 years, p=0.037). Combining the genotype risk, those with high risk of SNPs in both genes had a 70% cumulative incidence of ONJ within 24 months from initiation of ZA versus 17% for those carrying one of the two SNPs and 0% for those without any high risk of SNPs (p<0.001). In conclusion, our data indicate that SNPs in the CYP2C8 and PPAR-γ genes are associated with a risk of early development of ONJ. However, increasing cumulative dose of ZA increases substantially the risk of ONJ in all patients, independently of genotype-defined risk. Disclosures No relevant conflicts of interest to declare.

Osteonecrosis of the jaw associated with intravenous bisphosphonate therapy—A single institution experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18553-18553 ◽  
Author(s):  
E. M. Wallace ◽  
K. I. Quintyne ◽  
B. M. Cantwell ◽  
P. M. Calvert ◽  
G. D. Leonard
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Zoledronic Acid ◽  
Metastatic Breast ◽  
Median Number ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Unknown Primary ◽  
Dental Procedures ◽  
Increased Risk

18553 Background: Osteonecrosis of the jaw (ONJ) is a debilitating disease that has been associated with cancer therapy. Recently a link between ONJ and chronic intravenous (IV) bisphosphonates has been suggested. We assessed the incidence of ONJ and its risk factors in patients treated with IV bishosphonates at our institution. Methods: All patients with a cancer diagnosis treated at our institution with at least four cycles of either IV Zoledronic Acid, Pamidronate, or a combination of both, from 2000–2005 were evaluated using outpatient records. Patients with ONJ were identified and their characteristics were compared to all patients receiving bisphosphonate therapy. Results: One hundred and twenty-one patients were evaluated, 36 Male and 85 Female. Median age- 62 (Range 34–85). Seventy-six had metastatic Breast cancer, 25 Prostate, 7 Lung, 3 Colorectal, 3 Renal, 2 unknown primary, 1 each of Penile, Bladder, Seminoma, Lymphoma and Melanoma. Forty patients received Pamidronate infusions alone, 51 Zoledronic Acid alone and 30 a combination of the two. The median number of Pamidronate infusions was 8 (Range 4–10), Zoledronic infusions 10.7 (Range 4–32), and a combination of pamidronate and zoledronic acid was 12 (Range 5–66). Three patients developed ONJ. All 3 patients were female, had a median age of 62 (range 52–74) and had metastatic breast cancer. The median number of bisphosphonate infusions prior to the development of ONJ was 35 (Range 18–47). All patients had chest wall radiotherapy and 1 had chemotherapy and steroids. No patients had dental procedures or prolonged antibacterial therapy. Conclusions: ONJ is a complication associated with IV Bisphosphonate therapy. Our study suggests that female sex, zoledronic acid, and prolonged administration of bisphosphonates, may confer an increased risk for the development of ONJ. Further prospective studies with adequate power are needed to clarify what patients are most at risk for developing ONJ and what measures are needed to prevent its occurrence. No significant financial relationships to disclose.

Zoledronic acid for hormone-naive prostate cancer with bone metastasis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16092-e16092
Author(s):  
Masahiro Nozawa ◽  
Isao Hara ◽  
Kazuhiro Nagao ◽  
Hideyasu Matsuyama ◽  
Hirotsugu Uemura
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Osteonecrosis Of The Jaw ◽  
Bone Diseases ◽  
Free Survival ◽  
Early Introduction ◽  
Treatment Naïve

e16092 Background: The potency of zoledronic acid for hormone-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefit of administering zoledronic acid concomitant with androgen-deprivation therapy in treatment-naïve prostate cancer patients with bone metastases, in which the primary endpoint was skeleton-related event (SRE)-free survival at 24 months after treatment. Methods: Treatment-naïve male patients with histologically confirmed adenocarcinoma of the prostate and radiologic evidence of bone metastasis were eligible. Treatment consisted of bicalutamide 80 mg administered orally on Day 1 and every day, goserelin acetate 10.8 mg administered subcutaneously on Day 8 and every 12 weeks, and zoledronic acid 4 mg administered intravenously on Day 8 and every four weeks. Results: Between July 2008 and April 2010, a total of 53 patients were enrolled and 52 evaluable. Median age was 72 years (range, 55 - 86). Median primary PSA was 249.4 ng/ml (range, 2.19 –19201). Median follow-up period was 33.3 months. The SRE-free survival rate at 24 months after treatment was 82.7 %. Median time to PSA progression was 25.9 months (95% confidential interval, 17.97-24.43). The score of the extent of bone diseases was stable or decreased in 73 % of the patients at 24 months after treatment. The grade-3 osteonecrosis of the jaw was reported in three patients (5.8 %). Conclusions: Our results suggest the potency of the early introduction of zoledronic acid for prostate cancer patients with bone metastases. Future studies are certainly required to ascertain the most appropriate timing of the commencement of zoledronic acid for patients with bone-metastatic prostate cancer. Clinical trial information: UMIN000007548.

Genetic factors related with early onset of osteonecrosis of the jaw in patients with multiple myeloma under zoledronic acid therapy

2017 ◽  
Vol 58 (10) ◽  
pp. 2304-2309 ◽  
Author(s):  
Efstathios Kastritis ◽  
Pelagia Melea ◽  
Tina Bagratuni ◽  
Ioannis Melakopoulos ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Early Onset ◽  
Genetic Factors ◽  
Osteonecrosis Of The Jaw ◽  
Acid Therapy

Incidence and risk factors of bisphosphonate associated osteonecrosis of the jaws

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9074-9074
Author(s):  
M. Stumpe ◽  
R. Chandra ◽  
F. Yunus ◽  
S. Samant
Keyword(s):  
Risk Factors ◽  
Zoledronic Acid ◽  
Drug Exposure ◽  
Single Case ◽  
Case Reports ◽  
Drug Dose ◽  
Bisphosphonate Therapy ◽  
Bone Diseases ◽  
Duration Of Treatment ◽  
Dosing Interval

9074 Background: Intravenous bisphosphonate therapy has been used for treatment of various benign and malignant bone diseases, including bony metastasis. Recent single case reports have described osteonecrosis (ON) of the mandible or maxilla as a previously unknown complication of this therapy. Methods: Records of 638 patients treated with intravenous pamidronate or zoledronic acid were reviewed to determine the incidence of jaw ON. Number of infusions, dosing interval, dosage administered, and duration of treatment were analyzed to determine risk factors for the development of this complication. Results: Mean age of the study group was 67 years and 61% were female. The most common primary malignancies included prostate, lung, breast, and multiple myeloma. The overall incidence of osteonecrosis was 6/638 (0.94%). Patients treated with pamidronate (n=336), zoledronic acid (n=169), and both agents (n=133) had an incidence of ON of 1.2%, 0%, and 1.5% respectively (p=NS). No significant relationship was observed between the incidence of ON and demographic parameters, primary tumor, cumulative drug dose, or dosing interval. However, patients who developed ON had a significantly greater mean number of infusions (20.7 versus 10.7, p=0.016) and significantly greater mean hours of infusion time (42.7 versus 17.7, p=0.0036) than those who did not develop the complication. Underlying dental disease appears to be associated with ON. Conclusions: This review represents the largest single series to date of patients treated with IV bisphosphonate therapy. The findings suggest positive correlation between the development of ON and drug exposure as measured by number of infusions and total infusion hours. However, this data must be interpreted with caution as the overall incidence of the complication was low (<1%), precluding rigorous statistical analysis. Dental comorbidity should be addressed prior to initiation of bisphosphonate therapy. No significant financial relationships to disclose.

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