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Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of...
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Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw

A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 10733

Special Issue Editor

Dr. Matthias Tröltzsch

E-Mail Website
Guest Editor
1. Department of Oral, Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Munich, Germany
2. Center for Oral, Maxillofacial and Facial Plastic Surgery, Ansbach, Germany
Interests: medication-related osteonecrosis of the jaw; head and neck oncology; odontogenic sinusitis; facial plastic and reconstructive surgery

Special Issue Information

Dear Colleagues,

Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known pathology for oral health care providers. MRONJ mainly develops in patients undergoing treatment with antiresorptive drugs (bisphosphonates, denosumab). However, the list of other agents with possible implications in the etiology of MRONJ, such as inhibitors of thyrosine kinases, angiogenesis or immunological pathways, is growing. The scientific knowledge about the pathomechanism, prevention concepts, diagnostic methods and therapeutic algorithms of MRONJ is evolving rapidly.  Several countries have published guidelines for the management of MRONJ.

While it may seem that the management of MRONJ is based on a sufficient scientific basis, there are still many knowledge gaps to be filled. The exact interrelationships between the mechanisms of action of the MRONJ triggering drugs and cellular pathways have to clarified in further detail, and the gained information must be translated into clinical medicine. While the efficacy of prophylactic measures against MRONJ occurrence can be assumed from clinical studies, prospectively designed studies are necessary to provide scientific proof. New therapeutic aspects (non-invasive, minimally invasive and invasive) should be tested and studied in order to improve treatment outcomes. This includes the implementation of tissue engineering techniques, new surgical approaches and innovative reconstructive concepts. The options of safe and predictable dental rehabilitation of MRONJ sites (with or without the use of dental implants) with respect to the affected patients’ quality of life should be further elucidated.

I kindly invite you to submit your innovative research to this Special Issue. It shall function as a platform for experimental, translational and clinical science exchange regarding all aspects of MRONJ research and further advance our knowledge in this field so that we can improve the management of MRONJ patients.

Thanks for your time and effort!

Sincerely,

Dr. Matthias Tröltzsch
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • MRONJ
  • pathomechanisms
  • translational medicine
  • prophylaxis
  • conservative treatment
  • surgical treatment
  • jaw reconstruction techniques
  • dental restoration
  • implantology and MRONJ

Published Papers (6 papers)

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13 pages, 2939 KiB  
Article
Evaluation of Preventive Role of Systemically Applied Erythropoietin after Tooth Extraction in a Bisphosphonate-Induced MRONJ Model
by Gonca Duygu, Gül Merve Yalcin-Ülker, Murat Günbatan, Merva Soluk-Tekkesin and Ceyda Özcakir-Tomruk
Medicina 2023, 59(6), 1059; https://doi.org/10.3390/medicina59061059 - 31 May 2023
Cited by 2 | Viewed by 1155
Abstract
Background and Objectives: In this experimental study, the prophylactic effect of systemically administered erythropoietin (EPO) in medication-related osteonecrosis of the jaw (MRONJ) was evaluated. Materials and Methods: The osteonecrosis model was established using 36 Sprague Dawley rats. EPO was systemically applied [...] Read more.
Background and Objectives: In this experimental study, the prophylactic effect of systemically administered erythropoietin (EPO) in medication-related osteonecrosis of the jaw (MRONJ) was evaluated. Materials and Methods: The osteonecrosis model was established using 36 Sprague Dawley rats. EPO was systemically applied before and/or after tooth extraction. Groups were formed based on the application time. All samples were evaluated histologically, histomorphometrically, and immunohistochemically. A statistically significant difference in new bone formation was observed between the groups (p < 0.001). Results: When new bone-formation rates were compared, no significant differences were observed between the control group and the EPO, ZA+PostEPO, and ZA+Pre-PostEPO groups (p = 1, 0.402, and 1, respectively); however, this rate was significantly lower in the ZA+PreEPO group (p = 0.021). No significant differences in new bone formation were observed between the ZA+PostEPO and ZA+PreEPO groups (p = 1); however, this rate was significantly higher in the ZA+Pre-PostEPO group (p = 0.009). The ZA+Pre-PostEPO group demonstrated significantly higher intensity level in VEGF protein expression than the other groups (p < 0.001). Conclusions: Administering EPO two weeks pre-extraction and continuing EPO treatment for three weeks post-extraction in ZA-treated rats optimized the inflammatory reaction, increased angiogenesis by inducing VEGF, and positively affected bone healing. Further studies are needed to determine the exact durations and doses. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
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20 pages, 4337 KiB  
Article
Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model)
by Matthias Troeltzsch, Stephan Zeiter, Daniel Arens, Dirk Nehrbass, Florian A. Probst, Paris Liokatis, Michael Ehrenfeld and Sven Otto
Medicina 2023, 59(5), 1000; https://doi.org/10.3390/medicina59051000 - 22 May 2023
Cited by 3 | Viewed by 1745
Abstract
Background and Objectives: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli [...] Read more.
Background and Objectives: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? Materials and Methods: A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. Results: Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. Conclusions: The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
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11 pages, 347 KiB  
Article
Comparing the Influence of Surgical and Conservative Therapy on Quality of Life in Patients with Early-Stage Medication-Related Osteonecrosis of the Jaw—A Prospective Longitudinal Study
by Thomas Rückschloß, Maximilian Smielowski, Julius Moratin, Gregor Schnug, Maximilian Appel, Philipp Muench, Moritz Bleymehl, Sven Zittel, Michael Engel, Jürgen Hoffmann and Oliver Ristow
Medicina 2023, 59(2), 277; https://doi.org/10.3390/medicina59020277 - 31 Jan 2023
Cited by 2 | Viewed by 1185
Abstract
Background and Objectives: The purpose of this study was to evaluate the impact of surgical and conservative, non-surgical treatment on general health-related (QoL) and oral health-related quality of life (OHRQoL) in patients suffering from AAOMS stage I MRONJ. Materials and Methods: In [...] Read more.
Background and Objectives: The purpose of this study was to evaluate the impact of surgical and conservative, non-surgical treatment on general health-related (QoL) and oral health-related quality of life (OHRQoL) in patients suffering from AAOMS stage I MRONJ. Materials and Methods: In the course of this prospective clinical study, QoL and OHRQoL using QLQ-C30 and QHIP G14 questionnaire were longitudinally assessed in N = 174 prospectively enrolled patients with indication of treatment of MRONJ stage I over a period of 12 months. Patients received conservative or surgical treatment. The measurement time points were preoperatively (T0), 12 weeks (T1), 6 months (T2) and 1 year after operation (T3). Results: For OHRQoL, no significant (p > 0.05) differences were found between both treatment groups for all timepoints (T0–T3). In the surgical treatment group, OHIP scores of T1, T2 and T3 were significantly lower than baseline measures (T0) (T0–T1 (2.99, p = 0.024), T0–T2 (5.20, p < 0.001), T0–T3 (7.44, p < 0.001)). For conservative treatment group OHIP, scores of T2 and T3 were significantly lower than baseline measures (T0) (T0–T2 (9.09, p = 0.013), T0–T3 (12.79, p < 0.001)). There was no statistically significant effect of time on QLQ-C30 scores in both groups (surgical treatment: F(3, 174) = 1.542, p < 0.205, partial η2 = 0.026; conservative treatment: F(3, 30) = 0.528, p = 0.667, partial η2 = 0.050). QLQ-C30 scores turned out to be significantly lower in the non-surgical group at T1 (p = 0.036) and T3 (p = 0.047) compared to the surgical treatment group. Conclusions: Surgical and conservative treatment of MRONJ stage I significantly improves patients’ OHRQoL. Surgical treatment is superior to conservative treatment of MRONJ stage I regarding general QoL. Therefore, surgical treatment of MRONJ stage I should not be omitted for QoL reasons. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
17 pages, 727 KiB  
Article
Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) in Terms of Staging and Treatment Strategies by Dental Students at Different Educational Levels
by Diana Heimes, Nicolas Alexander Mark, Robert Kuchen, Andreas Pabst, Philipp Becker, Solomiya Kyyak, Daniel G. E. Thiem, Ralf Schulze and Peer W. Kämmerer
Medicina 2023, 59(2), 252; https://doi.org/10.3390/medicina59020252 - 28 Jan 2023
Viewed by 1563
Abstract
Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist’s ability to correctly diagnose the disease. Methods [...] Read more.
Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist’s ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students’ lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease’s context and X-ray diagnostics is needed. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
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17 pages, 9283 KiB  
Article
The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages
by Roberto Sacco, Suelen Cristina Sartoretto, Rodrigo Figueiredo de Brito Resende, Jose de Albuquerque Calasans-Maia, Alexandre Malta Rossi, Victor Hugo de Souza Lima, Carlos Fernando de Almeida Barros Mourão, Jose Mauro Granjeiro, Julian Yates and Monica Diuana Calasans-Maia
Medicina 2023, 59(1), 46; https://doi.org/10.3390/medicina59010046 - 27 Dec 2022
Cited by 1 | Viewed by 2007
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk [...] Read more.
Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29–34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89–26.48) (p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment (p = 0.001). Conclusions: HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
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16 pages, 15888 KiB  
Case Report
MRONJ of the Mandible—From Decortication to a Complex Jaw Reconstruction Using a CAD/CAM-Guided Bilateral Scapula Flap
by Robin Kasper, Mario Scheurer, Sebastian Pietzka, Andreas Sakkas, Alexander Schramm, Frank Wilde and Marcel Ebeling
Medicina 2023, 59(3), 535; https://doi.org/10.3390/medicina59030535 - 09 Mar 2023
Cited by 2 | Viewed by 2362
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) has been an integral part of the maxillofacial patient population for some time. The therapeutic concept ranges from conservative approaches over less extended decortications to major jaw resections, which can result in a considerable loss of quality [...] Read more.
Medication-related osteonecrosis of the jaw (MRONJ) has been an integral part of the maxillofacial patient population for some time. The therapeutic concept ranges from conservative approaches over less extended decortications to major jaw resections, which can result in a considerable loss of quality of life. Based on three case reports, this paper presents the long-term history of patients with MRONJ of the mandible, whose disease ultimately resulted in partial or total mandibular resection and subsequent multisegmental reconstruction using a microvascular anastomosed bone flap. Furthermore, a suitable alternative for complex mandibular reconstruction is demonstrated when using a free fibula flap is not possible. The options are limited, particularly when multisegmental restoration of mandibular continuity is required. One case presents a mandible reconstruction using a CAD/CAM-guided bilateral scapular free flap (CAD/CAM = Computer-Aided Design and Manufacturing), which has not been described for this purpose before. Due to the complexity, computer-assisted surgery and patient-specific implants seem reasonable, which is why a special focus was applied to this topic. Full article
(This article belongs to the Special Issue Advances in Prevention and Management Concepts of Medication-Related Osteonecrosis of the Jaw)
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