Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Lorenzo-Pouso, Alejandro I.; Bagán, José; Bagán, Leticia; Vila, Pilar Gándara; Chamorro-Petronacci, Cintia; Castelo‐Baz, Pablo; Carrión, Andrés Blanco; Blanco-Fernández, María Ángeles; Alvarez-Calderon, Oscar; Carballo, Javier; Pérez‐Sayáns, Mario

doi:10.3390/jcm10194367

Cited by 15 publications

(28 citation statements)

References 133 publications

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“…Its incidence varies widely from 0.4% to 12% [ 1 , 3 ] and can reach 28% [ 4 ]. Further research is needed to refine the epidemiology of these MRONJ estimates [ 5 , 6 ]. These medications inhibit bone remodeling and are used to treat osteoporosis or bone metastases.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in 2020, 353 articles were published on PubMed, including 28 meta-analyses and 10 randomized clinical trials (RCTs). Although there are many publications on the management of MRONJ, there is currently no consensus on the ideal treatment protocol [ 6 ] or measurable effects of therapeutics. Recent studies show that adverse events still occur, and the incidence rate remains stable despite the harmful consequence of anti-resorptive drugs for patients [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations

Gaudet

Odet

Meyer

et al. 2022

Cells

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Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations

Gaudet

Odet

Meyer

et al. 2022

Cells

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“…Currently, standard medical care for MRONJ is still lacking, along with evidence about the most effective treatment strategies [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The medical treatments that are effective in the control of signs and symptoms of MRONJ are systemic antibiotics, the use of antibacterial mouth rinses (e.g., chlorhexidine) and the maintenance of good oral hygiene. Additionally, superficial debridement of exposed bony spicula can improve patient discomfort, especially at an early disease stage [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Temporary Denosumab Discontinuation Promotes Bone Healing of Osteonecrosis of the Jaw and Minimizes the Invasiveness of Surgery: A Case Presentation

Bettini

Saia

Benetello

et al. 2022

Oral

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Denosumab has proved effective at low doses in increasing bone mineral density in osteoporosis patients. In contrast to high-doses antiresorptive therapy, denosumab has a transient effect on the inhibition of the bone remodeling process, suggesting that denosumab-related osteonecrosis is a self-limiting disease, with a high curative potential of surgery when performed after a proper duration of receptor activator of nuclear factor-kB ligand (RANKL) inhibitor suspension. We report the long-term clinical and radiological (Computed Tomography—CT scan) data of a patient affected by secondary osteoporosis (cancer treatment-induced bone loss—CTIBL for metastatic breast cancer) who underwent surgical treatment for stage II denosumab-related osteonecrosis of the upper maxilla 7 months after denosumab suspension. A minimally invasive approach was performed with the extraction of the first right upper molar and debridement of the surrounding alveolar bone. After surgery, the patient was followed up at three-month intervals up to 1 year, and clinical and radiological data (CT scan) were recorded at each follow-up for the early detection of signs of recurrent disease. The mucosal healing remained stable in the long term, with radiological signs of bone remodeling in the post-operative site since the 6-month follow-up. The presented case strengthens the hypothesis that denosumab induces temporary alterations of bone turnover with a predictable curative effect of minimal surgical procedures in cases of denosumab-related osteonecrosis of the jaw.

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“…Although the mechanisms of MRONJ onset is still unclear, the following factors are suggested to be associated with or to contribute to increase the risks for MRONJ onset: suppression of osteoclast activity, inhibition of angiogenesis, reduced blood flow, decrease in immunity, increase in oral bacterial infection, and inhibition of epithelial cell migration [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration

Tanaka

Aung

Ono

et al. 2021

IJMS

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Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-β superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, β-tricalcium phosphate (β-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/β-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/β-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/β-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/β-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/β-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/β-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/β-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

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Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review

Cited by 15 publications

References 133 publications

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations

Temporary Denosumab Discontinuation Promotes Bone Healing of Osteonecrosis of the Jaw and Minimizes the Invasiveness of Surgery: A Case Presentation

Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration

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