scholarly journals Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis

2012 ◽  
Vol 27 (10) ◽  
pp. 2130-2143 ◽  
Author(s):  
J Ignacio Aguirre ◽  
Mohammed P Akhter ◽  
Donald B Kimmel ◽  
Jennifer E Pingel ◽  
Alyssa Williams ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Osteonecrosis Of The Jaw ◽  
Oryzomys Palustris

scholarly journals Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Moe Mouri ◽  
Hideaki Tomita ◽  
Masaki Hirabatake ◽  
Mai Ikemura ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Tooth Extraction ◽  
Proportional Hazards ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Patients With Cancer ◽  
Proportional Hazards Regression ◽  
Before And After ◽  
Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

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

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.

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.

Low-dose dexamethasone and thalidomide with higher frequency zoledronic acid (dtZ) for newly diagnosed multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18506-18506
Author(s):  
G. Teoh ◽  
D. Tan ◽  
C. Chuah ◽  
W. Hwang ◽  
R. Yiu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Complete Remission ◽  
Median Time ◽  
Low Dose ◽  
Dental Treatment ◽  
Osteonecrosis Of The Jaw ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
The Individual

18506 Background: Although dexamethasone (Dex), thalidomide (Thal) and zoledronic acid (Zol) have frequently been combined for the treatment of multiple myeloma (MM), the ideal dosing schedule is unknown. We previously reported that lower doses of Dex and Thal can be effectively combined with high-frequency dosing of Zol (Haematologica 2005). Methods: This “dtZ” regimen - which comprises weekly Dex 20 mg OM for 4 days, Thal 50 mg ON, and 3-weekly Zol 4 mg - resulted in an impressive response rate (RR) of 61.6% and near complete remission (nCR)/complete remission (CR) rate of 7.7% in 26 patients with relapsed/refractory MM. Results: In this present study, we treated 22 newly diagnosed MM patients with “dtZ” and report an even more impressive RR of 100.0% and nCR/CR rate of 20–35%. The median time to response was 1.8 months and median time to maximum response was 2.2 months. The median time to progression (TTP) has not been achieved yet. As expected, low-dose Dex/Thal resulted in lower (18.1%) grade 3 or 4 toxicities. These were all infections; which lead to further dose-reduction of Dex. There were no thromboembolic events, despite the fact that aspirin was not routinely given. Of particular interest, 3- weekly Zol was not associated with any significant decrease in renal function, and none of our patients developed osteonecrosis of the jaw (ONJ). In fact, at the time of writing of this abstract, more than 1,000 doses of Zol had been administered in a 3-weekly fashion to these as well as other patients, and only 1 patient developed ONJ. This patient who had already received greater than 20 doses of Zol healed uneventfully after receiving appropriate outpatient dental treatment, and subsequently received another 8 doses of Zol with no recurrence of ONJ. Conclusion: In conclusion, the Zol-based “dtZ” regimen is potentially a highly-effective and safe frontline regimen for MM. Using Zol every 3 weeks with lower doses of Dex and Thal does not appear to increase the rate or severity of nephrotoxicity or ONJ. Although we do not know exactly why every patient responded to “dtZ”, we speculate that this could be due to a critical balance that has been achieved between the anti-MM, anti-osteoclastic and immunostimulatory effects of the individual drugs of the combination. No significant financial relationships to disclose.

Zoledronic acid (ZOL) treatment (Rx) of ≥2 years in patients (pts) with metastatic bone disease (MBD) or multiple myeloma (MM): Six-month results from the LOTUZ study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9630-9630
Author(s):  
L. Duck ◽  
M. Delforge ◽  
C. Doyan ◽  
H. Wildiers ◽  
K. MacDonald ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Bone Disease ◽  
Osteonecrosis Of The Jaw ◽  
Metastatic Bone Disease ◽  
Skeletal Related Events ◽  
Dental Conditions ◽  
Term Data

9630 Background: The bisphosphonate (BP) ZOL is frequently used to prevent skeletal-related events (SRE) in cancer pts. However, data are limited on its use beyond 2 years. LOTUZ is among the first studies to examine Rx and outcomes in pts with ZOL Rx for >2y. We report 6-month results. Methods: Prospective (18m), multicenter (50), pharmacoepidemiologic study. Baseline (0m) and 6m data available on 205 pts (of 298 enrolled), all free from osteonecrosis of the jaw (ONJ) at 0m. Prior to ZOL Rx, 27.8% had non-ZOL BP Rx. Mean pre-enrollment BP duration was 42 mo (23–145) with 38 mo (23–80) for ZOL. Results: Mean age: 64 y (38–88); M/F: 29/71%; 67.8% with MBD vs 32.2% MM. 89.3% continued ZOL RX 0–6m; 90% with dose 4mg. From 0–6m, 10 pts (4.8%) developed ONJ (4 with MM, 6 with MBD): 5 mild, 3 moderate, 2 severe (median BP duration: 38.4, 46.5, and 34.8 months, respectively). Five pts with ONJ continued on ZOL RX 0–6m (3 mild, 2 moderate). 4/10 pts with ONJ had baseline dental conditions or procedures, 8/10 at 6m (only 1/10 at neither). SREs and pain levels remained constant 0–6m compared to 6m prior to baseline (see Table ). Conclusions: Beyond 2y, 90% of pts were continued on ZOL. SREs did not increase, but ONJ was diagnosed in 10/205 pts 0–6m, of which 5 were on ZOL RX beyond 24m. Long-term data are needed to better understand the risk/benefit of long-term ZOL Rx. [Table: see text] [Table: see text]

Osteonecrosis of the jaw in patients treated with sunitinib and zoledronic acid.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e15116-e15116 ◽  
Author(s):  
G. Bozas ◽  
V. Allgar ◽  
G. Greenwood ◽  
A. Maraveyas
Keyword(s):  
Zoledronic Acid ◽  
Osteonecrosis Of The Jaw

Osteonecrosis of the jaw in patients with cancer receiving zoledronic acid for bone metastases: SWOG S0702, NCT00874211.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11502-11502 ◽  
Author(s):  
Catherine H. Van Poznak ◽  
Joseph M. Unger ◽  
Amy K. Darke ◽  
Carol Moinpour ◽  
Robert A. Bagramian ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Cumulative Incidence ◽  
Oral Surgery ◽  
Clinical Care ◽  
Osteonecrosis Of The Jaw ◽  
Care Plan ◽  
Cancer Type ◽  
Cancer Treatments ◽  
True Incidence ◽  
Dosing Intervals

11502 Background: Osteonecrosis of the jaw (ONJ) may occur in cancer patients (pts) with metastatic bone disease (MBD) treated with bone modifying agents. No large prospective studies have precisely determined the incidence of ONJ. A better understanding of the true incidence and predictors of ONJ is needed. Methods: SWOG S0702 was a prospective observational study that assessed the cumulative incidence (CI) of ONJ at 3 years in pts with MBD from any malignancy receiving zoledronic acid (Zol). Participants must have had either limited or no prior exposure to bone modifying agents and a clinical care plan that included use of Zol within 30 days of registration. Cancer treatments, bone modifying agents (including Zol), and dental care were administered as clinically indicated and were not directed by S0702. Baseline and every 6 m followup dental exams were recommended. Report forms (medical, dental and pt reported outcomes) were submitted every 6 m but if ONJ was diagnosed, follow up interval became every 3 m. Protocol defined ONJ required exposed bone in the maxillofacial region present 8 weeks or more in a pt who was receiving or had been exposed to a bisphosphonate, and had not had radiation therapy to the craniofacial region. Results: The study enrolled 3,491 evaluable pts (breast 1,120; myeloma 580; prostate 702, lung 666, other 423) between 2009-2013. About 2/3 of pts had a baseline dental exam. Overall, 87 pts had confirmed ONJ. The cumulative incidence of ONJ was 0.8% at year 1 (95% CI: 0.5%-1.1%), 2.0% at year 2 (95% CI: 1.5%-2.5%), and 2.8% at year 3 (95% CI: 2.3-3.5%). Rates of 3-year confirmed ONJ were highest in myeloma pts (4.3%; 95% CI, 2.8%-6.4%). Pts with planned Zol dosing intervals of every 3-4 weeks (n = 3,032, 87.2%) were much more likely to experience ONJ than pts with planned dosing intervals of 5 weeks or greater (n = 447, 12.8%; 3.2% vs 0.7%; HR = 4.80, 95% CI, 1.52-15.18, p = .008). Fewer total number of teeth, the presence of dentures and any oral surgery at baseline were all associated with a higher rate of ONJ. Conclusions: About 1 in 40 patients receiving Zol for MBD developed ONJ. S0702 provides information to guide stratification of risk for developing ONJ in pts with MBD receiving Zol. Cancer type, oral health and frequency of Zol dosing affect risk of ONJ. Clinical trial information: NCT00874211.

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