The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the MRONJ Patients and Control Subjects
2.2. Results of Microbiological Analyses: Traditional Qualitative and Quantitative Culture and PCR
2.3. Microbiota Composition of Bone Samples from MRONJ Patients and Controls
3. Discussion
4. Materials and Methods
4.1. Study Design and Setting, Inclusion and Exclusion Criteria
4.2. Bone Sampling Procedure
4.3. Microbiological Processing of Samples, Traditional Qualitative and Quantitative Culture Methods
4.4. DNA Extraction and PCR Amplification
4.5. DNA Isolation, 16S rRNA Gene Library Preparation Protocol and MiSeq Sequencing
4.6. Statistical Analysis
4.7. Ethical Considerations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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MRONJ Patients (n = 35) | Controls (n = 35) | p-Value | |||
---|---|---|---|---|---|
Age | |||||
Median [years] (minimum–maximum) | 70 (40–87) | 35 (17–78) | p < 0.001 (Mann-Whtiney U test) | ||
n | % | n | % | ||
Sex | |||||
Male | 16 | 45.7 | 18 | 51.4 | n.s. (χ2-test) |
Female | 19 | 54.3 | 17 | 48.6 | |
Co-morbidities | |||||
Hypertension (HT) | 24 | 68.5 | 5 | 14.3 | p = 0.004 (Fisher’s exact test) |
Diabetes mellitus (DM) | 11 | 30.9 | 3 | 8.6 | p < 0.001 (Fisher’s exact test) |
HT and DM | 10 | 28.6 | 0 | 0 | p < 0.001 (Fisher’s exact test) |
Obesity (BMI ≥ 30) | 1 | 3.0 | 0 | 0 | n.s. (Fisher’s exact test) |
Lifestyle factors | |||||
Tobacco consumption (T) | 12 | 34.3 | 19 | 54.3 | n.s. (χ2-test) |
Alcohol consumption (A) | 6 | 17.1 | 9 | 25.7 | n.s. (Fisher’s exact test) |
T and A | 5 | 14.3 | 3 | 8.6 | n.s. (Fisher’s exact test) |
Illicit substance use | 0 | 0 | 0 | 0 | n.s. (Fisher’s exact test) |
Indication for antiresorptive treatment | |||||
Prostate cancer | 14 | 39.9 | n.r. | ||
Breast cancer | 11 | 30.9 | |||
Lung cancer | 3 | 8.6 | |||
Kidney cancer | 3 | 8.6 | |||
Colon cancer | 1 | 3.0 | |||
Myeloma multiplex (MM) | 1 | 3.0 | |||
Osteoporosis | 1 | 3.0 | |||
Langerhans-hystiocytosis | 1 | 3.0 | |||
MRONJ staging | |||||
Stage I. | 3 | 8.6 | n.r. | ||
Stage II. | 19 | 54.3 | |||
Stage III. | 13 | 37.1 | |||
Localization of primary lesion | |||||
Maxilla | 12 | 34.3 | n.r. | ||
Mandible | 22 | 62.8 | |||
Both jawbones | 1 | 2.9 |
MRONJ Patients Number of Isolates (n = 185 overall) | Controls Number of Isolates (n = 72 overall) | |
---|---|---|
Gram-positive anaerobic rods | n = 54 overall | n = 25 overall |
Abiotrophia adiacens | 1 | 0 |
A. defectiva | 1 | 1 |
Actinotignum schaalii | 2 | 0 |
A. naeslundii | 10 | 2 |
A. oralis | 2 | 0 |
A. oris | 5 | 4 |
A. viscous | 1 | 0 |
Gleimella europaeus | 1 | 0 |
Schaalia meyeri | 1 | 0 |
S. odontolytica | 13 | 2 |
S. turicensis | 1 | 0 |
Bifidobacterium dentium | 2 | 0 |
B. longum | 1 | 0 |
Clostridium beijernickii | 2 | 0 |
Cutibacterium acnes | 0 | 2 |
C. avidum | 2 | 0 |
C. namnetense | 0 | 1 |
Eggerthella lenta | 0 | 4 |
Eubacterium brachy | 1 | 0 |
E. cataniformis | 1 | 0 |
E. cellulosolvens | 1 | 0 |
Filifactor alocis | 1 | 1 |
Lactobacillus paracasei | 1 | 0 |
Lachroanaerobaculum orale | 0 | 7 |
Lacticaseibacterium spp. | 0 | 1 |
Paraclostridium bifermentans | 1 | 0 |
Solobacterium moorei | 3 | 0 |
Gram-positive anaerobic cocci | n = 30 overall | n = 9 overall |
Gemella haemolisans (morbillorum) | 2 | 0 |
G. sanguis | 0 | 1 |
Lactococcus lactis | 1 | 0 |
Lancefieldella rimae | 2 | 0 |
Oslenella uli | 1 | 0 |
Parvimonas micra | 11 | 5 |
Peptoniphilus lacrimalis | 1 | 0 |
P. stomatis | 8 | 3 |
Peptoniphilus spp. | 2 | 0 |
Peptostreptococcus anaerobius | 2 | 0 |
Gram-negative anaerobic rods | n = 71 overall | n = 15 overall |
Aggregatibacterium aphrophilus | 1 | 1 |
Bacteroides fragilis | 2 | 0 |
Campylobacter rectus | 2 | 0 |
Capnocytophaga sputigena | 2 | 0 |
Dialister microaerophilus | 1 | 0 |
Eikenella corrodens | 6 | 0 |
Fusobacterium canaliformis | 2 | 0 |
F. mortiferum | 1 | 0 |
F. necrophorum | 3 | 0 |
F. nucleatum | 15 | 6 |
F. periodonticum | 0 | 1 |
F. varium | 1 | 0 |
Leptotrichia hofstadii | 1 | 0 |
L. wadei | 2 | 1 |
L. trevisani | 1 | 0 |
Porphyromonas gingivalis | 5 | 0 |
P. somerae | 1 | 0 |
Prevotella baroniae | 1 | 0 |
P. buccae | 5 | 2 |
P. buccalis | 1 | 0 |
P. dentalis | 1 | 0 |
P. denticola | 5 | 2 |
P. heparinolytica | 1 | 0 |
P. intermedia | 2 | 1 |
P. jejuni | 1 | 0 |
P. melaninogenica | 1 | 0 |
P. nigrescens | 3 | 0 |
P. oralis | 1 | 1 |
Selenomonas artemidis | 1 | 0 |
S. sputigena | 1 | 0 |
Slackia exigua | 1 | 0 |
Gram-negative anaerobic cocci | n = 30 overall | n = 25 overall |
Veillonella atypica | 8 | 3 |
V. dispar | 2 | 1 |
V. parvula | 16 | 18 |
V. rogosae | 4 | 3 |
Sample ID | Culture Results Actinomyces or ALO Species Recovered | Colony Forming Units (CFU/mg) | Results of PCR Analyses | |||
---|---|---|---|---|---|---|
MRONJ Cases | Controls | MRONJ Cases | Controls | MRONJ Cases | Controls | |
1 | A. naeslundii | A. naeslundii | 109 | 104 | + | + |
2 | S. odontolytica | negative | 106 | 0 | + | + |
3 | A. schaalii | negative | 109 | 0 | + | + |
4 | A. naeslundii S. odontolytica A. oralis | negative | 109 106 105 | 0 | + | − |
5 | negative | negative | 0 | 0 | + | − |
6 | negative | negative | 0 | 0 | + | − |
7 | A. oralis | negative | 104 | 0 | + | − |
8 | S. odontolytica A. oralis | negative | 109 | 0 | + | + |
9 | S. odontolytica A. oris | A. naeslundii | 109 | 105 | + | − |
10 | S. odontolytica | S. odontolytica A. oris | 109 | 105 | + | − |
11 | negative | negative | 0 | 0 | − | − |
12 | A. naeslundii S. odontolytica | negative | 109 | 0 | + | + |
13 | negative | negative | 0 | 0 | − | − |
14 | S. odontolytica A. oris | A. oris | 109 | 104 | + | + |
15 | negative | negative | 0 | 0 | + | − |
16 | S. odontolytica G. europaeus | A. oris | 109 | 105 | + | + |
17 | A. naeslundii S. odontolytica | negative | 109 | 0 | + | − |
18 | A. naeslundii | negative | 105 | 0 | + | − |
19 | S. odontolytica S. meyeri | negative | 109 | 0 | + | + |
20 | A. naeslundii A. oris | negative | 109 | 0 | + | − |
21 | negative | negative | 0 | 0 | − | − |
22 | S. odontolytica | negative | 108 | 0 | + | − |
23 | A. schaalii A. naeslundii | S. odontolytica A. oris | 107 | 104 | + | + |
24 | A. naeslundii S. odontolytica | negative | 105 | 0 | + | + |
25 | S. odontolytica A. oris | negative | 105 | 0 | + | − |
26 | negative | negative | 0 | 0 | + | − |
27 | negative | negative | 0 | 0 | + | + |
28 | A. naeslundii A. oris | negative | 107 | 0 | + | − |
29 | S. turicensis | negative | 105 | 0 | + | − |
30 | A. naeslundii A. viscous | negative | 105 | 0 | + | − |
31 | negative | negative | 0 | 0 | − | + |
32 | negative | negative | 0 | 0 | + | − |
33 | A. oris | negative | 104 | 0 | + | − |
34 | negative | negative | 0 | 0 | − | − |
35 | negative | negative | 0 | 0 | − | − |
Samples | ||||
---|---|---|---|---|
K1 | K2 | K3 | K4 | K5 |
Veillonella: 55.10% | Streptococcus: 93.89% | Veillonella: 54.67% | Veillonella: 50.40% | Streptococcus: 95.4% |
Fusobacterium: 17.41% | Cutibacterium: 3.35% | Parvimonas: 30.33% | Peptostreptococcus: 21.64% | Bacteroides: 0.35% |
Parvimonas: 9.07% | Prevotella: 0.30% | Streptococcus: 3.83% | Haemophilus: 8.88% | Aquabacterium: 0.33% |
Eikenella: 4.65% | Sphingobium: 0.27% | Cryptobacterium: 2.98% | Streptococcus: 4.71% | Prevotella: 0.30% |
Actinobacillus: 3.26% | Porphyromonas: 0.27% | Cutibacterium: 1.91% | Dialister: 4.69% | Sphingobium: 0.29% |
Campylocbacter: 2.73% | Parvimonas: 0.22% | Olsenella: 1.79% | Stomatobaculum: 3.28% | Acinetobacter: 0.25% |
Haemophilus: 2.23% | Acinetobacter: 0.20% | Campylobacter: 0.98% | Solobacterium: 1.75% | Escherichia-Shigella: 0.22% |
Staphylococcus: 0.37% | Murdochiella: 0.14% | Shuttleworthia: 0.56% | Campylocbacter: 1.22% | Bradyrhizobium: 0.20% |
Granulicatella: 0.11% | Aquabacterium: 0.12% | Eikenella: 0.44% | Staphylococcus: 1.15% | Enhydrobacter: 0.12% |
Aggregatibacter: 0.06% | Bacteroides: 0.11% | Bifidobacterium: 0.44% | Lactiplantibacillus: 0.41% | Cutibacterium: 0.11% |
Bacteroides: 0.05% | Eschierichia-Shigella: 0.11% | Haemophilus: 0.28% | Shuttleworthia: 0.31% | Faecalibacterium: 0.09% |
Actinomyces: 0.05% | Atopoboium: 0.28% | Saccharimonas: 0.24% | Curvibacter: 0.08% | |
Centipeda: 0.20% | Atopobium: 0.19% | Staphylococcus: 0.08% | ||
Actinomyces: 0.19% | Prevotella: 0.13% | Parabacteroides: 0.08% | ||
Bacteroides: 0.05% | Cartonella: 0.10% | Allistipes: 0.07% | ||
Alloscardovia: 0.09% | Blautia: 0.06% | |||
Parvimonas: 0.08% | Atopostipes: 0.06% | |||
Fusobacterium: 0.07% | Agarthobacter: 0.05% | |||
Sphingobium: 0.05% | Finegoldia: 0.05% | |||
Actinomyces: 0.05% | Veillonella: 0.05% | |||
Parvimonas: 0.05% | ||||
(Actinomyces: 0.01%) |
Samples | ||||
---|---|---|---|---|
T1 | T2 | T3 | T4 | T5 |
Pyramidobacter: 32.35% | Morganella: 57.38% | Prevotella: 34.71% | Veillonella: 62.67% | Actinomyces: 38.50% |
Veillonella: 25.22% | Veillonella: 30.12% | Prevotella_7: 16.86% | Peptostreptococcus: 13.39% | Lacticaseibacillus: 24.39% |
Sphaerochaeta: 12.71% | Prevotella: 3.53% | Parvimonas: 13.82% | Dialister: 7.92% | Cutibacterium: 17.17% |
Dialister: 11.36% | Peptostreptococcus: 2.36% | Streptococcus: 12.70% | Parvimonas: 7.48% | Staphylococcus: 16.81% |
Peptostreptococcus: 5.15% | Dialister: 1.25% | Eikenella: 11.50% | Haemophilus: 2.20% | Scardovia: 1.05% |
Acidaminococcus: 4.20% | Prevotella_7: 1.12% | Dialister: 4.07% | Slackia: 0.85% | Sphingobium: 0.20% |
Selenomonas: 2.22% | Parvimonas: 1.08% | Staphylococcus: 3.19% | Streptococcus: 0.73% | Aquabacterium: 0.20% |
Anaeroglobulus: 1.76% | Streptococcus: 0.82% | Oribacterium: 1.58% | Staphylococcus: 0.65% | Acinetobacter: 0.15% |
Campylobacter: 1.51% | Oribacterium: 0.51% | Actinomyces: 0.46% | Prevotella: 0.60% | Bacteroides: 0.13% |
Prevotella: 0.98% | Asteroleplasma: 0.29% | Granulicatella: 0.19% | Atopobium: 0.40% | Escherichia-Shigella: 0.09% |
Streptococcus: 0.57% | Actinomyces: 0.20% | Bidifobacterium: 0.17% | Prevotella_7: 0.025% | Enhydrobacter: 0.06% |
Fusobacterium: 0.55% | Gemella: 0.15% | Eikenella: 0.13% | ||
Lacticaseibacillus 0.38% | Catonella: 0.09% | |||
Bifidobacterium 0.35% | Neisseria: 0.09% | |||
Slackia: 0.33% | Rothia: 0.06% | |||
Oribacterium: 0.18% | Actinomyces: 0.06% | |||
Prevotella_7: 0.16% | ||||
Treponema: 0.12% | ||||
Eikenella: 0.10% | ||||
Parvimonas: 0.10% | ||||
Bacteroides: 0.07% | ||||
Actinomyces: 0.05% | ||||
Phascolarctobacterium: 0.05% |
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Kövér, Z.; Gajdács, M.; Polgár, B.; Szabó, D.; Urbán, E. The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods. Antibiotics 2025, 14, 203. https://doi.org/10.3390/antibiotics14020203
Kövér Z, Gajdács M, Polgár B, Szabó D, Urbán E. The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods. Antibiotics. 2025; 14(2):203. https://doi.org/10.3390/antibiotics14020203
Chicago/Turabian StyleKövér, Zsanett, Márió Gajdács, Beáta Polgár, Dóra Szabó, and Edit Urbán. 2025. "The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods" Antibiotics 14, no. 2: 203. https://doi.org/10.3390/antibiotics14020203
APA StyleKövér, Z., Gajdács, M., Polgár, B., Szabó, D., & Urbán, E. (2025). The Microbiological Background of Medication-Related Osteonecrosis of the Jaw (MRONJ): Clinical Evidence Based on Traditional Culture and Molecular Biological Detection Methods. Antibiotics, 14(2), 203. https://doi.org/10.3390/antibiotics14020203