A Retrospective Observational Study of Risk Factors for Denosumab-Related Osteonecrosis of the Jaw in Patients with Bone Metastases from Solid Cancers
Abstract
:1. Introduction
2. Results
2.1. Patient Demographics and Characteristics
2.2. Comparison of DRONJ and Non-DRONJ Patients
2.3. Risk Factors for DRONJ
3. Discussion
4. Patients and Methods
4.1. Data Sources and Search Strategy
4.2. Inclusion and Exclusion Criteria
4.3. Study Variables
4.4. Study Outcomes
4.5. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Description | n (%) or Median (Range) | ||
---|---|---|---|
Demographic factors | Sex | Male | 57 (46.3) |
Female | 66 (53.7) | ||
Age (years) | 68.0 (25.0–95.0) | ||
Performance status | 0 | 0 (0.0) | |
1 | 11 (8.9) | ||
2 | 51 (41.5) | ||
3 | 52 (42.3) | ||
4 | 9 (7.3) | ||
Height (cm) | 158.0 (130.0–178.0) | ||
Weight (kg) | 51.4 (27.6–77.2) | ||
BMI 1 | 20.6 (13.3–31.0) | ||
Oral nutrition | Yes | 122 (99.2) | |
Brinkman index | 0.0 (0.0–2460.0) | ||
Alcohol consumption | Yes | 10 (8.1) | |
Medical history | Diabetes mellitus | Yes | 16 (13.0) |
Rheumatoid arthritis | Yes | 4 (3.3) | |
Hypocalcemia | Yes | 60 (48.8) | |
Hypercalcemia | Yes | 0 (0.0) | |
Hypothyroidism | Yes | 4 (3.3) | |
Osteoporosis | Yes | 7 (5.7) | |
Vitamin B deficiency | Yes | 1 (0.8) | |
Anemia | Yes | 85 (69.1) | |
Antithrombotic therapy | Yes | 19 (15.4) | |
Blood parameters | Hemoglobin (g/dL) | 11.4 (6.3–17.7) | |
Total protein (g/dL) | 6.7 (4.1–8.4) | ||
Albumin (g/dL) | 3.4 (1.5–4.6) | ||
Cholesterol (mg/dL) | 180.0 (53.0–337.0) | ||
Calcium (mg/dL) | 8.9 (6.2–10.2) | ||
C-reactive protein (mg/dL) | 1.6 (0.0–23.7) | ||
Underlying disease | Cancer type | Breast | 32 (26.0) |
Lung | 24 (19.5) | ||
Prostate | 16 (13.0) | ||
Colon | 13 (10.6) | ||
Pancreas | 6 (4.9) | ||
Kidney | 7 (5.7) | ||
Liver | 8 (6.5) | ||
Uterus | 2 (1.6) | ||
Stomach | 6 (4.9) | ||
Bladder | 3 (2.4) | ||
Other | 6 (4.9) | ||
Bone metastasis | Yes | 123 (100) | |
Multiple metastases | Yes | 67 (54.5) | |
Chemotherapy and/or molecular targeted drug | Yes | 34 (27.6) | |
Angiogenesis inhibitor | Yes | 0 (0.0) | |
Tyrosine kinase inhibitor | Yes | 0 (0.0) | |
Hormonal therapy | Yes | 23 (18.7) | |
Intraoral findings | Number of teeth | 18.0 (0.0–32.0) | |
Denture use | Yes | 48 (39.0) | |
Apical periodontitis | Yes | 44 (35.8) | |
Periodontal disease | Yes | 54 (43.9) | |
Denosumab | Administration period (months) | 4 (2–52) | |
Reason for dropout | Continuing | 40 (32.5) | |
Cancelled | 2 (1.6) | ||
Deceased | 81 (65.9) | ||
Follow-up (months) | 4 (2–52) | ||
DRON J 2 | DRONJ 2 stage [18] | 0 | 0 (0.0) |
1 | 3 (2.4) | ||
2 | 5 (4.1) | ||
3 | 6 (4.9) |
Variables | n (%) or Median (Range) | ||||
---|---|---|---|---|---|
Control (n = 109) | DRONJ (n = 14) | p-Value | |||
Background factor | Sex | Male | 55 (50.5) | 2 (14.3) | 0.011 * |
Female | 54 (49.5) | 12 (85.7) | |||
Age (years) | 68.0 (25.0–95.0) | 64.0 (51.0–77.0) | 0.155 | ||
Performance status | 0 | 0 (0.0) | 0 (0.0) | 0.422 | |
1 | 10 (9.2) | 1 (7.1) | |||
2 | 43 (39.4) | 8 (57.1) | |||
3 | 48 (44.0) | 4 (28.6) | |||
4 | 8 (7.3) | 1 (7.1) | |||
Height (cm) | 160.0 (130.0–178.0) | 152.0 (145.0–164.0) | 0.010 * | ||
Weight (kg) | 51.4 (27.6–77.2) | 53.3 (31.0–72.5) | 0.469 | ||
BMI 1 | 20.4 (13.3–28.7) | 21.7 (13.4–31.0) | 0.055 | ||
Oral nutrition | Yes | 108 (99.1) | 14 (100) | 1.000 | |
Brinkman index | 0.0 (0.0–2460.0) | 0 (0.0–0.0) | 0.001 ** | ||
Alcohol consumption | Yes | 10 (9.2) | 0 (0.0) | 0.602 | |
Medical history | Diabetes mellitus | Yes | 15 (13.8) | 1 (7.1) | 0.692 |
Rheumatoid arthritis | Yes | 3 (2.8) | 1 (7.1) | 0.387 | |
Hypocalcemia | Yes | 55 (50.5) | 5 (35.7) | 0.397 | |
Hypercalcemia | Yes | 0 (0.0) | 0 (0.0) | - | |
Hypothyroidism | Yes | 4 (3.7) | 0 (0.0) | 1.000 | |
Osteoporosis | Yes | 5 (4.6) | 2 (14.3) | 0.181 | |
Vitamin B deficiency | Yes | 1 (0.9) | 0 (0.0) | 1.000 | |
Anemia | Yes | 76 (69.7) | 9 (64.3) | 0.761 | |
Antithrombotic therapy | Yes | 17 (15.6) | 2 (14.3) | 1.000 | |
Blood examination | Hemoglobin (g/dL) | 11.2 (6.3–17.7) | 11.9 (8.3–15.9) | 0.097 | |
Total protein (g/dL) | 6.7 (4.1–8.4) | 7.0 (5.6–7.8) | 0.170 | ||
Albumin (g/dL) | 3.4 (1.5–4.6) | 3.3 (2.6–4.5) | 0.385 | ||
Cholesterol (mg/dL) | 179.0 (53.0–337.0) | 201.5 (146.0–334.0) | 0.232 | ||
Calcium (mg/dL) | 8.9 (6.2–10.0) | 9.2 (6.4–10.2) | 0.187 | ||
C-reactive protein (mg/dL) | 1.7 (0.0–23.7) | 1.0 (0.0–4.7) | 0.136 | ||
Underlying disease | Cancer type | Breast | 21 (10.3) | 11 (78.6) | - |
Lung | 24 (22.0) | 0 (0.0) | |||
Prostate | 14 (12.8) | 2 (14.3) | |||
Colon | 12 (11.0) | 1 (7.1) | |||
Pancreatic | 6 (5.5) | 0 (0.0) | |||
Kidney | 7 (6.4) | 0 (0.0) | |||
Liver | 8 (7.3) | 0 (0.0) | |||
Uterus | 2 (1.8) | 0 (0.0) | |||
Stomach | 6 (5.5) | 0 (0.0) | |||
Bladder | 3 (2.8) | 0 (0.0) | |||
Other | 6 (5.5) | 0 (0.0) | |||
Bone metastasis | Yes | 109 (100) | 14 (100) | - | |
Multiple metastases | Yes | 56 (51.4) | 11 (78.6) | 0.085 | |
Chemotherapy or molecular targeted drug | Yes | 26 (23.9) | 8 (57.1) | 0.021 * | |
Angiogenesis inhibitor | Yes | 0 (0.0) | 0 (0.0) | - | |
Tyrosine kinaseinhibitor | Yes | 0 (0.0) | 0 (0.0) | - | |
Hormonal therapy | Yes | 16 (14.7) | 7 (50.0) | 0.005 ** | |
Intraoral findings | Number of teeth | 17.0 (0.0–32.0) | 21.5 (0.0–32.0) | 0.717 | |
Denture use | Yes | 41 (37.6) | 7 (50.0) | 0.395 | |
Apical periodontitis | Yes | 34 (31.2) | 10 (71.4) | 0.006 ** | |
Periodontal disease | Yes | 42 (38.5) | 12 (85.7) | 0.001 ** | |
Denosumab | Administration period (months) | 4 (2–52) | 10 (7–45) | 0.001 ** | |
Drop out reason | Continuing | 32 (29.4) | 8 (57.1) | - | |
Cancelled | 1 (0.9) | 1 (7.1) | |||
Deceased | 76 (69.7) | 5 (35.7) | |||
DRONJ 2 | DRONJ 2 stage [18] | 0 | 0 (0.0) | 0 (0.0) | - |
1 | 0 (0.0) | 3 (21.4) | |||
2 | 0 (0.0) | 5 (35.7) | |||
3 | 0 (0.0) | 6 (42.9) |
Variables | Univariate | Multivariate | ||
---|---|---|---|---|
Odds Ratio (CI) | Significance | Odds Ratio (CI) | Significance | |
Hormonal therapy | 5.81 (1.80–18.81) | 0.003 | 22.07 (2.86–170.24) | 0.003 |
Chemotherapy/molecular target drug | 4.26 (1.35–13.40) | 0.013 | 18.61 (2.54–136.27) | 0.004 |
Apical periodontitis | 5.52 (1.62–18.84) | 0.006 | 22.75 (3.20–161.73) | 0.002 |
Periodontal disease | 9.57 (2.04–44.91) | 0.004 | ||
Sex | 6.11 (1.31–28.60) | 0.022 | ||
Body mass index | 1.18 (1.02–1.37) | 0.024 |
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Okuma, S.; Matsuda, Y.; Nariai, Y.; Karino, M.; Suzuki, R.; Kanno, T. A Retrospective Observational Study of Risk Factors for Denosumab-Related Osteonecrosis of the Jaw in Patients with Bone Metastases from Solid Cancers. Cancers 2020, 12, 1209. https://doi.org/10.3390/cancers12051209
Okuma S, Matsuda Y, Nariai Y, Karino M, Suzuki R, Kanno T. A Retrospective Observational Study of Risk Factors for Denosumab-Related Osteonecrosis of the Jaw in Patients with Bone Metastases from Solid Cancers. Cancers. 2020; 12(5):1209. https://doi.org/10.3390/cancers12051209
Chicago/Turabian StyleOkuma, Satoe, Yuhei Matsuda, Yoshiki Nariai, Masaaki Karino, Ritsuro Suzuki, and Takahiro Kanno. 2020. "A Retrospective Observational Study of Risk Factors for Denosumab-Related Osteonecrosis of the Jaw in Patients with Bone Metastases from Solid Cancers" Cancers 12, no. 5: 1209. https://doi.org/10.3390/cancers12051209
APA StyleOkuma, S., Matsuda, Y., Nariai, Y., Karino, M., Suzuki, R., & Kanno, T. (2020). A Retrospective Observational Study of Risk Factors for Denosumab-Related Osteonecrosis of the Jaw in Patients with Bone Metastases from Solid Cancers. Cancers, 12(5), 1209. https://doi.org/10.3390/cancers12051209