Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Eligibility Criteria
- -
- patients suffering from BC commencing, taking or who had taken BMAs for CTIBL
- -
- at least 12 months of dental follow-up.
2.3. Outcome Measures
2.4. Statistical Analysis
3. Results
Characteristics of Patients
4. Discussion
- (1)
- cancer patients with BM or myeloma patients; generally receiving high dose BMAs often associated with other agents (chemotherapy, endocrine therapy, immunotherapy, antiangiogenics and other biological agents) (high MRONJ risk) [19];
- (2)
- breast cancer (BC) or prostate cancer patients suffering from osteoporosis without bone metastases receiving bisphosphonates or denosumab to limit the risk of non-metastatic bone fractures (due to CTIBL); this population (assuming the same dosage of BMAs) is considered assumable to those with osteoporosis for what concern their MRONJ risk [20];
- (3)
- patients suffering from osteoporosis and other non-malignant diseases; receiving BMAs with different regimens (low MRONJ risk) [21];
- -
- from the beginning of BMAs administration to within 3 years from the commencing of the treatment, a patient who does not report other MRONJ risk factors (e.g., systemic and/or local) will be classified and considered at low risk of MRONJ.
- -
- if the patient has been in treatment for a period of time longer than 3 years or shorter than 3 years and simultaneously affected by systemic or local risk factors, this patient will bear an incremental and indefinable risk of developing MRONJ, which is linked to one or more additional, reported systemic or local risk factors.
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient | Age | Systemic Disease | Local Risk Factors | ONJ-Related Drugs | Duration (Months) | Cumulative Doses (mg) | Dental Extractions | N. Teeth Extracted | MRONJ Onset during Follow-Up | Time-Lapse between 1st° Visit and Last Check-Up (Months) |
---|---|---|---|---|---|---|---|---|---|---|
#1 | 53 | Autoimmune thyroiditis | Poor oral hygiene, dental prosthesis | alendronate clodronate | 48 12 | 13,440 2400 | No | n.a. | No | 12 |
#2 | 79 | Arthrosis, diabetes | Poor oral hygiene | clodronate | 120 | 24,000 | No | n.a. | No | 14 |
#3 | 73 | Hypertension, arthrosis, diabetes, hepatitis C | Poor oral hygiene | clodronate | 82 | 16,400 | No | n.a. | No | 19 |
#4 | 83 | n.a. | Poor oral hygiene | clodronate | 132 | 26,400 | No | n.a. | No | 12 |
#5 | 75 | n.a. | Dental prosthesis, periodontal disease, poor oral hygiene, endo-periodontal lesion | risedronate Xgeva® | 48 60 | 7200 7200 | Yes | 2 | Yes | 84 |
#6 | 57 | Hypertension, osteomalacia | endo-periodontal lesion | alendronate | 12 | 3360 | Yes | 2 | No | 42 |
#7 | 70 | Hypertension | Dental prosthesis, periodontal disease, poor oral hygiene | alendronate | 156 | 43,680 | Yes | 1 | No | 36 |
#8 | 48 | Thalassaemia carrier | n.a. | alendronate | 33 | 9240 | Yes | 2 | No | 40 |
#9 | 67 | N.a. | n.a. | clodronate | 12 | 2400 | No | n.a. | No | 12 |
#10 | 71 | Hepatitis C | Periodontal disease, poor oral hygiene | alendronate Xgeva® | 48 4 | 13,440 480 | Yes | 4 | No | 30 |
#11 | 51 | Hypertension | Dental prosthesis | alendronate Prolia® | 20 12 | 5600 120 | Yes | 3 | No | 23 |
#12 | 84 | Hypertension | Poor oral hygiene | clodronate Xgeva® | 24 20 | 4800 2400 | No | n.a. | No | 12 |
#13 | 56 | N.a. | Periodontal disease, poor oral hygiene | Prolia® zoledronate | 20 16 | 180 64 | Yes | 3 | Yes | 21 |
#14 | 66 | N.a. | Dental prosthesis, periodontal disease, poor oral hygiene | alendronate | 44 | 3360 | No | n.a. | No | 36 |
Number of Patients | Median and Standard Deviation | % | ||
---|---|---|---|---|
Low dose BMA for CTIBL | 14 | |||
alendronate | 6 | - | 42.9% | |
clodronate | 6 | - | 42.9% | |
risedronate | 1 | - | 7.1% | |
Prolia® | 1 | - | 7.1% | |
Duration of low dose BMAs therapy (mths) | 57.9 (±47.1) | - | ||
High dose BMA for BM | 4 | |||
zoledronate | 1 | - | 25% | |
Xgeva® | 3 | - | 75% | |
Duration of DNB therapy (mths) | 3 | 28 (±23.6) | - | |
Duration of ZOL therapy (mths) | 1 | 16 | - |
Patient | Age | Sex | MTS | MRONJ after the Pharmacological Switch | ONJ-Related Drgs | Duration (Months) | Cumulative Dosi (mg) | ONJ Localization | ONJ Stage According to SIPMO-SICMF3 | ONJ Stage According to AAOMS16 | Clinical Features |
---|---|---|---|---|---|---|---|---|---|---|---|
#1 | 75 | F | Yes | Yes | risedronate Xgeva® | 48 60 | 7200 7200 | Anterior lower jaw | I | Intraoral Fistula, Tooth mobility | |
#2 | 56 | F | Yes | Yes | Prolia® zoledronate | 20 16 | 180 64 | Posterior upper jaw | I | Tooth mobility | |
#3 | 71 | F | Yes | No | alendronate Xgeva® | 48 4 | 13,440 480 | n.a. | n.a. | n.a. | n.a. |
#4 | 84 | F | Yes | No | clodronate Xgeva® | 24 20 | 4800 2400 | n.a. | n.a. | n.a. | n.a. |
Characteristics | Patients under Only Low Dose BMAs (No Case of MRONJ) | Patients under Low + High Dose BMAs (No Case of MRONJ) | Patients under Low + High Dose BMAs (Onset of MRONJ) | |
---|---|---|---|---|
N patients | 10 | 2 | 2 | |
Age | Range | 48–83 | 71–84 | 56–75 |
Median | 65.5 | 77.5 | 65.5 | |
Standard deviation | 11.7 | 9.2 | 13.4 | |
Smoking habit | 1 | 0 | 0 | |
Systemic disease | Hypertension | 4 | 1 | 0 |
Diabetes | 2 | 0 | 0 | |
Arthrosis | 2 | 0 | 0 | |
Local risk factors | Poor oral hygiene | 7 | 2 | 2 |
Dental prosthesis | 4 | 0 | 1 | |
Periodontal disease | 2 | 2 | 1 | |
Endo-periodontal lesion | 1 | 0 | 1 | |
Bone MTS | 0 | 2 | 2 | |
Low dose MRONJ- related drugs durations (months) | 67.1 (±52.9) | 36 (±17) case #1: 48 mths case#2: 24 mths | 34 (±19.8) case #1: 48 mths case#2: 20 mths | |
Low dose MRONJ- related drugs cumulative dose (mg) | 14,788 (±13,286.3) | 9120 (±6109.4) case #1: 13,440 mg case #2: 4800 mg | 3690 (±4963.9) case #1: 7200 mg case #2: 180 mg | |
High dose MRONJ- related drugs durations (months) | n.a. | 12 (±11.3) Case #1: 4 mths Case#2: 20 mths | 38 (±31.1) Case #1: 60 mths Case#2: 16 mths | |
High dose MRONJ- related drugs cumulative dose (mg) | n.a. | 1440 (±1357.6) Case #1: 480 mg Case #2: 2400 mg | 3632 (±5045.9) Case #1: 7200 mg Case #2: 64 mg | |
Dental surgery | N patients | 4 (40%) | 1 (50%) | 2 (100%) |
N extracted teeth | 8 | 4 | 3 | |
Jaw | Upper | 5 | 3 | 2 |
Lower | 3 | 1 | 1 | |
Follow-up (months) | 24.6 (±12.6) | 21 (±12.7) | 52.5 (±44.5) |
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Mauceri, R.; Coppini, M.; Campisi, G. Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study. Oral 2022, 2, 274-285. https://doi.org/10.3390/oral2040026
Mauceri R, Coppini M, Campisi G. Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study. Oral. 2022; 2(4):274-285. https://doi.org/10.3390/oral2040026
Chicago/Turabian StyleMauceri, Rodolfo, Martina Coppini, and Giuseppina Campisi. 2022. "Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study" Oral 2, no. 4: 274-285. https://doi.org/10.3390/oral2040026
APA StyleMauceri, R., Coppini, M., & Campisi, G. (2022). Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study. Oral, 2(4), 274-285. https://doi.org/10.3390/oral2040026