Interventions for managing medication‐related osteonecrosis of the jaw
Information
- DOI:
- https://doi.org/10.1002/14651858.CD012432.pub3Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 12 July 2022see what's new
- Type:
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- Intervention
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Oral Health Group
- Copyright:
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- Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Authors
Contributions of authors
Drafted the protocol: NB, OZ
Wrote the protocol: NB, OZ
Developed the search strategy: NB, OZ, and Anne Littlewood (Information Specialist from Cochrane Oral Health)
Selected trials: NB, HH, OZ
Extracted data: NB, JP, HH, OZ
Assessed trial for risk of bias: NB, HH, OZ
Assessed certainty of the evidence: NB, OZ
Contacted authors of ongoing RCTs: OZ
Performed statistical analysis: NB, BM, OZ
Wrote the review: NB, JP, OZ
Produced 'Summary of findings' table: NB, JP, OZ
Sources of support
Internal sources
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Division of Dentistry, The University of Manchester; Manchester Academic Health Sciences Centre (MAHSC); and the NIHR Manchester Biomedical Research Centre, UK, UK
Support to Cochrane Oral Health
External sources
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National Institute for Health Research (NIHR), UK
This project was supported by the NIHR, via Cochrane Infrastructure funding to Cochrane Oral Health. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
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Cochrane Oral Health Global Alliance, Other
The production of Cochrane Oral Health reviews has been supported financially by our Global Alliance since 2011 (oralhealth.cochrane.org/partnerships-alliances). Contributors in recent years have been the American Association of Public Health Dentistry, USA; AS‐Akademie, Germany; the British Association for the Study of Community Dentistry, UK; the British Society of Paediatric Dentistry, UK; the Canadian Dental Hygienists Association, Canada; the Centre for Dental Education and Research at All India Institute of Medical Sciences, India; the National Center for Dental Hygiene Research & Practice, USA; New York University College of Dentistry, USA; and Swiss Society of Endodontology, Switzerland.
Declarations of interest
There are no financial conflicts of interest and the review authors declare that they do not have any associations with any parties who may have vested interests in the results of this review.
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Natalie H Beth‐Tasdogan: no interests to declare
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Benjamin Mayer: no interests to declare
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Heba Hussein: no interests to declare
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Jens‐Uwe Peter: no interests to declare
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Oliver Zolk: no interests to declare
Acknowledgements
This update: we wish to thank Anne Littlewood (Cochrane Oral Health) for her assistance with literature searching, Laura MacDonald (Cochrane Oral Health) for her help with the preparation of this review, and Tanya Walsh for her comments. We thank Heather Maxwell for final copy editing.
Previous version: we thank the editorial team at Cochrane Oral Health, especially Martin McCabe, Anne Littlewood, Laura MacDonald, Helen Wakeford, Tanya Walsh, Helen Worthington, and Jo Weldon. We would like acknowledge the external referees Professor Juliet Compston, Professor Thomas B Dodson, and Dr. Athanassios Kyrgidis for their helpful feedback, and Jason Elliot‐Smith for final copy editing of the protocol for this review.
Version history
| Published | Title | Stage | Authors | Version |
| 2022 Jul 12 | Interventions for managing medication‐related osteonecrosis of the jaw | Review | Natalie H Beth-Tasdogan, Benjamin Mayer, Heba Hussein, Oliver Zolk, Jens-Uwe Peter | |
| 2017 Oct 06 | Interventions for managing medication‐related osteonecrosis of the jaw | Review | Natalie H Beth‐Tasdogan, Benjamin Mayer, Heba Hussein, Oliver Zolk | |
| 2016 Nov 09 | Interventions for managing medication‐related osteonecrosis of the jaw (MRONJ) | Protocol | Natalie H Beth‐Tasdogan, Benjamin Mayer, Heba Hussein, Oliver Zolk | |
Differences between protocol and review
The main difference between the protocol and this 2022 version of the review is that we changed the follow‐up time inclusion criterion. We reduced the required follow‐up period from one year to six months in order to include more studies. We did this because the longer the follow‐up period, the more participants drop out ‐ mainly due to progressive cancer ‐ and thus impair the significance of the analysis. Although Hinson 2015 reported delayed healing of MRONJ with a median time of 10 months in participants who received antiresorptive treatment and three to six months in patients who discontinued antiresorptive therapy, Park 2017 reported complete healing of MRONJ after four weeks or delayed healing after 16 weeks in patients receiving antiresorptive therapy. Finally, three treatment studies reported a follow‐up period of only six months (Ohbayashi 2020; Park 2017; Yüce 2021), and five treatment studies reported a longer follow‐up period of at least one year, but most of these also report primary or secondary outcomes at six months (Freiberger 2012; Giudice 2018a; Giudice 2018b; Ristow 2016; Sim 2020). Regarding prophylaxis studies, we can consider prophylaxis successful if there are no signs of MRONJ within eight weeks after surgery according to AAOMS criteria.
Notes
This is an update of a review published in 2017 (Beth‐Tasdogan 2017).
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Humans; Male;
PICOs
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Comparison 1: Dental examinations at three‐month intervals and preventive treatments (experimental) versus standard care (control) for prophylaxis of MRONJ, Outcome 1: MRONJ (incidence proportion)
Comparison 1: Dental examinations at three‐month intervals and preventive treatments (experimental) versus standard care (control) for prophylaxis of MRONJ, Outcome 2: MRONJ (incidence rate: MRONJ cases per patient‐year)
Comparison 2: Plasma rich in growth factors inserted into the postextraction alveolus in addition to standardised medical and surgical care (experimental) versus standardised medical and surgical care alone (control) for prophylaxis of MRONJ, Outcome 1: MRONJ (incidence proportion)
Comparison 3: Subperiosteal wound closure versus epiperiosteal wound closure after tooth extraction for prevention of MRONJ in patients on antiresorptive treatment, Outcome 1: MRONJ after tooth extraction (assessed with: absence of complete mucosal integrity) at 6 months
Comparison 4: Hyperbaric oxygen as an adjunct to conventional therapy (experimental) versus conventional therapy (control) for treatment of MRONJ, Outcome 1: Healing of MRONJ at last contact
Comparison 5: Autofluorescence‐guided bone surgery (experimental) versus tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ, Outcome 1: Healing of MRONJ (defined as mucosal integrity) at 1 year
Comparison 6: Bone morphogenetic protein‐2 together with platelet‐rich fibrin (experimental) compared to platelet‐rich fibrin alone (control) for treatment of MRONJ., Outcome 1: Healing of MRONJ (defined as full mucosal coverage without clinical or radiographical evidence of MRONJ) after 16 weeks
Comparison 7: Autofluorescence‐guided surgery (experimental) compared to conventional surgery (control) for treatment of MRONJ, Outcome 1: Healing of MRONJ (defined as full mucosal coverage and no signs of residual infection) at 1 year
Comparison 8: Platelet‐rich fibrin after bone surgery (experimental) compared to surgery alone (control) for treatment of MRONJ, Outcome 1: Healing of MRONJ (defined as absence of infection and mucosal integrity without fistula) at 1 year
Comparison 8: Platelet‐rich fibrin after bone surgery (experimental) compared to surgery alone (control) for treatment of MRONJ, Outcome 2: Healing of MRONJ (defined as absence of infection, mucosal integrity without fistula, and no need for re‐intervention) at 1 year
Comparison 9: Concentrated growth factor and primary wound closure (experimental) versus primary wound closure only (control) for treatment of MRONJ, Outcome 1: Healing of MRONJ (assessed with: mucosal integrity) at 6 months
Comparison 10: Teriparatide 20 μg daily (experimental) versus placebo (control), in addition to standard care, for treatment of MRONJ, Outcome 1: Healing of MRONJ (defined as absence of any unresolved lesion) at 1 year
Comparison 11: Teriparatide 56.5 μg weekly (experimental) versus teriparatide 20 μg daily (control), in addition to standard care, for treatment of MRONJ, Outcome 1: Healing of MRONJ (defined as partial or complete remission) at 6 months
| Dental examinations at three‐month intervals and preventive treatments (experimental) compared to standard care (control) for prophylaxis of MRONJ | ||||||
| Population: people at risk of MRONJ | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with standard care (control) | Risk with dental examinations at 3‐month intervals and preventive treatments (experimental) | |||||
| MRONJ (incidence proportion)
Follow‐up: mean 32 months | 233 per 1000 | 23 per 1000 | RR 0.10 | 253 | ⊕⊝⊝⊝ | Participants: high‐risk (i.e. individuals with cancer exposed to intravenous zoledronic acid). The outcome MRONJ was also reported as number of cases per patient‐year (incidence rate): rate ratio 0.18 (95% CI 0.04 to 0.74). |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to very serious risk of bias (high and unbalanced rate of crossovers after randomisation; high dropout rates due to high mortality; failure to adhere to the intention‐to‐treat principle; mean follow‐up differed between experimental and control groups) and very serious limitation of indirectness (all male and high‐risk patients). | ||||||
| Dental extraction protocol with plasma rich in growth factors (PRGF) (experimental) compared to a standard dental extraction protocol without PRGF (control) for prophylaxis of MRONJ in people treated with IV bisphosphonates who need dental extractions | ||||||
| Population: people treated with IV bisphosphonates who need dental extractions | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with standard dental extraction protocol without PRGF (control) | Risk with dental extraction protocol with PRGF (experimental) | |||||
| MRONJ (incidence proportion) Follow‐up: 24‐60 months | 59 per 1000 | 5 per 1000 | RR 0.08 | 176 | ⊕⊝⊝⊝ | Participants: high risk, i.e. individuals with cancer exposed to IV zoledronic acid |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of evidence by three levels due to imprecision and very serious risk of bias (high or unclear risk of selection bias, performance bias, detection bias, and attrition bias). | ||||||
| Subperiosteal wound closure versus epiperiosteal wound closure after tooth extraction for prevention of MRONJ in patients on antiresorptive treatment | ||||||
| Population: people on antiresorptive treatment | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with epiperiosteal wound closure after tooth extraction | Risk with subperiosteal wound closure after tooth extraction | |||||
| MRONJ after tooth extraction Assessed with: absence of complete mucosal integrity
Follow‐up: 6 months | 77 per 1000 | 7 per 1000 | RR 0.09 | 132 | ⊕⊕⊝⊝ | 8 patients changed intervention from epiperiosteal wound closure to subperiosteal wound closure. |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by two levels due to imprecision and serious risk of bias (unclear selection bias, detection bias, high risk of performance bias, attrition bias and reporting bias). | ||||||
| HBO as an adjunct to conventional therapy (experimental) compared to conventional therapy (control) for treatment of MRONJ | ||||||
| Population: people with MRONJ | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with conventional therapy (control) | Risk with HBO therapy as an adjunct to conventional therapy (experimental) | |||||
| Healing of MRONJ
Follow‐up: up to 24 months (outcome was measured at last follow‐up) | 333 per 1000 | 520 per 1000 | RR 1.56 | 46 (1 RCT) | ⊕⊝⊝⊝ |
|
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to imprecision and very serious risk of bias (unclear and high risk of selection bias, performance bias, detection bias, and attrition bias; failure to adhere to the intention‐to‐treat principle). | ||||||
| Autofluorescence‐guided bone surgery (experimental) compared to tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ | ||||||
| Population: people with MRONJ | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with tetracycline fluorescence‐guided bone surgery (control) | Risk with autofluorescence‐guided bone surgery (experimental) | |||||
| Healing of MRONJ
Follow‐up: 1 year | 889 per 1000 | 933 per 1000 | RR 1.05 | 34 | ⊕⊝⊝⊝ |
|
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to imprecision and very serious risk of bias (unclear and high risk of selection bias, performance bias, and detection bias). | ||||||
| Bone morphogenetic protein‐2 together with platelet‐rich fibrin (experimental) compared to platelet‐rich fibrin alone (control) for treatment of MRONJ | ||||||
| Population: people with MRONJ Settings: hospital Intervention: bone morphogenetic protein‐2 together with platelet‐rich fibrin (experimental) Comparison: platelet‐rich fibrin only (control) | ||||||
| Outcomes | Anticipated absolute risks* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with platelet‐rich fibrin only (control) | Risk with bone morphogenetic protein‐2 adjacent to platelet‐rich fibrin (experimental) | |||||
| Healing of MRONJ Defined in the study as full coverage with absence of exposed bone, mucosal swelling and erythema, purulent drainage, intra‐ and extra oral fistula and/or any pain or discomfort
Follow‐up: 16 weeks post surgery | 880 per 1000 | 968 per 1000 | RR 1.10 (0.94 to 1.29) | 55 | ⊕⊝⊝⊝
|
|
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to very serious limitations of imprecision and very serious risk of bias (unclear risk of selection bias, detection bias, high risk of performance bias, attrition bias, reporting bias). | ||||||
| Autofluorescence‐guided surgery (experimental) compared to conventional surgery (control) for treatment of MRONJ | ||||||
| Population: people with MRONJ Settings: hospital Intervention: autofluorescence guided surgery (experimental) Comparison: conventional surgery (control) | ||||||
| Outcomes | Anticipated absolute risks* (95% CI) | Relative effect | Number of Participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with conventional surgery (control) | Risk with autofluorescence guided surgery (experimental) | |||||
| Healing of MRONJ Criteria for healing: absence of bone exposure
Follow‐up: 1 year (at last follow‐up) | 867 per 1000 | 933 per 1000 | RR 1.08 (0.85 to 1.37) | 30 | ⊕⊝⊝⊝
| High drop‐out rate. 6 patients were excluded due to mortality and no show at follow‐up appointments. |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to very serious imprecision and serious risk of bias (high selection bias, performance bias, attrition bias, unclear risk of detection bias). | ||||||
| Platelet‐rich fibrin after bone surgery (experimental) compared to surgery alone (control) for treatment of MRONJ | ||||||
| Population: people with MRONJ Settings: hospital Intervention: platelet‐rich fibrin (experimental) Comparison: conventional (control) | ||||||
| Outcomes | Anticipated absolute risks* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with surgery alone (control) | Risk with platelet‐rich fibrin after bone surgery (experimental) | |||||
| Healing of MRONJ Defined as absence of infection and mucosal integrity without fistula
Follow‐up: 1 year | 913 per 1000 | 958 per 1000 | RR 1.05 (0.90 to 1.22) | 47 | ⊕⊝⊝⊝
| The outcome healing of MRONJ was also reported as absence of infection, mucosal integrity without fistula, no need for re‐intervention: rate ratio 1.60 (95% CI 1.04 to 2.46). Follow‐up: 1 year See Analysis 8.2. |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to very serious limitation of imprecision and serious risk of bias (unclear selection bias, detection bias, high risk of performance bias, reporting bias). | ||||||
| Concentrated growth factor and primary wound closure compared with primary wound closure only for treatment of MRONJ | ||||||
| Population: people with MRONJ | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with primary wound closure only (control) | Risk with concentrated growth factor and primary wound closure (experimental) | |||||
| Healing of MRONJ Defined as soft tissue healing Follow‐up: 6 months | 521 per 1000 | 286 per 1000 | RR 1.38 | 28 | ⊕⊝⊝⊝ |
|
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels because of serious risk of bias (unclear selection bias, high risk of performance bias), very serious limitation of indirectness (only female participants with osteoporosis) and very serious limitation of imprecision (few participants). | ||||||
| Teriparatide 20 μg daily compared with placebo for treatment of MRONJ | ||||||
| Population: people with MRONJ Settings: outpatient and inpatient treatment Intervention: teriparatide 20 μg daily Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of Participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo (control) | Risk with teriparatide 20 µg daily (experimental) | |||||
| Healing of MRONJ Primary outcomes were the clinical and radiologic resolution of MRONJ lesions, as evaluated by oral examination and CBCT imaging; secondary outcomes included improvement in MRONJ stage, change in MRONJ lesion size, quality of life, bone mineral density, and evidence of osteoblastic response measured biochemically using P1NP and radiologically using 18F‐fluoride PET‐CT imaging
Last follow‐up: 52 weeks | 278 per 1000 | 267 per 1000 (87 to 819) | RR 0.96 (0.31 to 2.95) | 33 (1 RCT) | ⊕⊕⊝⊝
|
|
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by two levels due to imprecision and serious risk of bias (unclear selection bias, high risk of attrition bias and reporting bias). | ||||||
| Teriparatide 56.5 μg weekly (experimental) compared with teriparatide 20 μg daily (control) in addition to standard care for treatment of MRONJ | ||||||
| Population: people with MRONJ Settings: outpatient and inpatient treatment Intervention: teriparatide 56.5 μg weekly in addition to standard care Comparison: teriparatide 20 μg daily in addition to standard care | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with teriparatide 20 μg daily (control) | Risk with teriparatide 56.5 µg weekly (experimental) | |||||
| Healing of MRONJ Measured changes in MRONJ clinical stage at 6 months after the start of the treatment as clinical course, changes in bone metabolism (using bone scintigraphy), percentage of bone formation on the osteolysis of MRONJ, and measurement of bone turnover markers)
Follow‐up: 6 months after start of treatment | 500 per 1000
| 300 per 1000 (125 to 721) | RR 0.60 (0.25 to 1.44) | 12 (1 RCT) | ⊕⊝⊝⊝
|
|
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1. We downgraded the certainty of the evidence by three levels due to imprecision and very serious risk of bias (unclear selection bias and detection bias, high risk of performance bias, attrition bias and reporting bias). | ||||||
| MRONJ stage | Description |
| AT RISK | No apparent necrotic bone in patients who have been treated with oral or intravenous bisphosphonates |
| STAGE 0 | No clinical evidence of necrotic bone but nonspecific clinical findings, radiographic changes, and symptoms |
| STAGE 1 | Exposed and necrotic bone or fistulas that probes to bone in patients who are asymptomatic and have no evidence of infection |
| STAGE 2 | Exposed and necrotic bone or fistulas that probes to bone associated with infection as evidenced by pain and erythema in the region of exposed bone with or without purulent drainage |
| STAGE 3 | Exposed and necrotic bone or a fistula that probes to bone in patients with pain, infection, and ≥ 1 of the following: exposed and necrotic bone extending beyond the region of alveolar bone (i.e. inferior border and ramus in mandible, maxillary sinus, and zygoma in maxilla) resulting in pathologic fracture, extraoral fistula, oral antral, or oral nasal communication, or osteolysis extending to inferior border of the mandible or sinus floor |
| From the American Association of Oral and Maxillofacial Surgeons position paper on medication‐related osteonecrosis of the jaw‐‐2014 update (Ruggiero 2014) | |
| The initial electronic search of 2016 retrieved 1105 references after de‐duplication. After screening the titles and abstracts, we excluded all but 23 references from further evaluation. We examined the full text of the remaining 23 articles and found that eight references relating to five studies met the prespecified inclusion criteria and were therefore included in this review. We identified four additional studies that are ongoing and listed these under Characteristics of ongoing studies. We excluded 11 full‐text articles for reasons noted in the Characteristics of excluded studies table. |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 MRONJ (incidence proportion) Show forest plot | 1 | 253 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.10 [0.02, 0.39] |
| 1.2 MRONJ (incidence rate: MRONJ cases per patient‐year) Show forest plot | 1 | Rate Ratio (IV, Fixed, 95% CI) | 0.18 [0.04, 0.74] | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 MRONJ (incidence proportion) Show forest plot | 1 | 176 | Risk Ratio (M‐H, Random, 95% CI) | 0.08 [0.00, 1.51] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 MRONJ after tooth extraction (assessed with: absence of complete mucosal integrity) at 6 months Show forest plot | 1 | 132 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.09 [0.00, 1.56] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Healing of MRONJ at last contact Show forest plot | 1 | 46 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.56 [0.77, 3.18] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Healing of MRONJ (defined as mucosal integrity) at 1 year Show forest plot | 1 | 34 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.86, 1.30] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Healing of MRONJ (defined as full mucosal coverage without clinical or radiographical evidence of MRONJ) after 16 weeks Show forest plot | 1 | 55 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.10 [0.94, 1.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Healing of MRONJ (defined as full mucosal coverage and no signs of residual infection) at 1 year Show forest plot | 1 | 30 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.08 [0.85, 1.37] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Healing of MRONJ (defined as absence of infection and mucosal integrity without fistula) at 1 year Show forest plot | 1 | 47 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.90, 1.22] |
| 8.2 Healing of MRONJ (defined as absence of infection, mucosal integrity without fistula, and no need for re‐intervention) at 1 year Show forest plot | 1 | 47 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.60 [1.04, 2.46] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Healing of MRONJ (assessed with: mucosal integrity) at 6 months Show forest plot | 1 | 28 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.38 [0.81, 2.34] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Healing of MRONJ (defined as absence of any unresolved lesion) at 1 year Show forest plot | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.31, 2.95] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 Healing of MRONJ (defined as partial or complete remission) at 6 months Show forest plot | 1 | 12 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.25, 1.44] |
