Interventions dans la prise en charge de l'ostéonécrose de la mâchoire liée aux médicaments
Referencias
References to studies included in this review
References to studies excluded from this review
References to ongoing studies
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of sequence generation not reported |
| Allocation concealment (selection bias) | Low risk | Quote: "The randomization of patients with MRONJ to treatment groups was performed after informed consent, but before the initial staging examination using a series of 70 opaque envelopes containing the assignment." |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "The subjects and staff were not blinded to therapy because of the impracticality of providing sham HBO; however, the oral‐maxillofacial surgeon was not told the subjects’ assignments before the initial staging examination." |
| Blinding of outcome assessment (detection bias) | High risk | Quote: "Lesion scores at the time of last contact were assigned by the study team, including the oral‐maxillofacial surgeon." No blinding of outcome assessment |
| Incomplete outcome data (attrition bias) | High risk | High attrition rate: at the 12‐ and 18‐month evaluations 50% and 63%, respectively, of participants were lost to follow‐up. High and unbalanced rate of cross‐overs: after randomisation 5 participants switched from the control to the HBO group; 1 participant assigned to the HBO group declined HBO treatment and was switched to the control group. Data analysis: as‐treated, not by intention‐to‐treat |
| Selective reporting (reporting bias) | Low risk | All outcome variables listed in the Methods and the study protocol were reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Quote: "Patients of each stage were randomly assigned to 1 of 2 surgical groups by an independent resident senior." |
| Allocation concealment (selection bias) | Unclear risk | Allocation concealment not reported |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel not reported. Due to the nature of the intervention, surgeons were not blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment not reported. |
| Incomplete outcome data (attrition bias) | High risk | Six participants excluded: 2 died during follow‐up and 4 did not attend the 6‐month follow‐up visit. |
| Selective reporting (reporting bias) | Low risk | All outcomes reported |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions | A combined antibiotic therapy with amoxicillin (1 g every 12 hours) and metronidazole (250 mg every 8 hours) for 10 days, beginning 3 days before surgery, a professional oral hygiene session and chlorhexidine 0.2% as a mouth rinse was performed in both groups. In case of hypersensitivity or allergy, clindamycin (600 mg 3 times a day) was received by participants.
All participants received a tension‐free wound closure with resorbable sutures and obtained routine postoperative instructions and the same postoperative drug therapy as before surgery. To avoid mucosal damage, no prosthesis should be used. | |
| Outcomes |
Outcomes evaluated preoperatively (T0) and at 1 month (T1), 6 months (T2), and 1 year (T3) after treatment
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "They were allocated to 2 groups according to their medication history: the first group included patients with bone metabolic disease being treated with a low‐dose (L) antiresorptive therapy (oral bisphosphonates, denosumab 60 mg/6 months) while the other group included patients with malignancy being treated with a high‐dose (H) antiresorptive therapy (intravenous bisphosphonates, denosumab 120 mg/4 weeks). Each group was divided in 2 subgroups by the same Senior Consultant (H2, L2 and H3, L3) according to the MRONJ stage diagnosed (stage 2 or 3)." "To create a homogeneous study population, an independent senior resident randomly assigned patients of each subgroup (H2, L2, H3, L3) to a specific surgical study group (PRF or non‐PRF)." Method of sequence generation not clearly described |
| Allocation concealment (selection bias) | Unclear risk | Allocation concealment not reported |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "The study was designed as a prospective randomized, single‐blind, monocentric clinical trial." |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors not reported |
| Incomplete outcome data (attrition bias) | Low risk | Follow‐up completed for all participants |
| Selective reporting (reporting bias) | High risk | Quote: "Data and clinical outcomes were collected by an independent resident preoperatively (T0) and at T1, T2, and T3." However, preoperative pain VAS scores were not reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
All participants: professional oral hygiene session 1 week before surgery; antibiotics for 6 days starting the evening before surgery, anaesthesia by alveolar nerve block, no intraligamentous or intrapapillary infiltrations; mucosal flap and suturing to enable healing via primary intention | |
| Outcomes |
Follow‐up examinations: mucosal healing was monitored at 3, 7, and 14 days postoperatively; monitoring for MRONJ was continued at 21, 30, 60, 90, and 120 days, and 6 months, followed by visits every 6 months | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "The study cohort was divided into two similar groups: 91 patients were treated with PRGF (study group) and 85 patients were not treated with the growth factor preparation (control group). The randomized group distribution was set up specifically to obtain groups that were homogenous for gender, age, smoking habits, systemic pathology based on the computerized clinical file we used in the first visit." Generation of randomisation sequence not reported |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | High risk | Due to the nature of the intervention, the personnel were not blinded. Because an extra 15 mL blood sample was obtained from the participants in the PRGF group, the participants were most likely not blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | It is not reported whether outcome was monitored by an independent and blinded outcome assessor. |
| Incomplete outcome data (attrition bias) | Unclear risk | Completeness or loss to follow‐up was not reported. |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions | All participants: professional oral hygiene session 1 week before surgery; antibiotics for 6 days starting the evening before surgery
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| Outcomes | Intraoperative complications
Follow‐up examinations: mucosal healing monitored at 3, 7, and 14 days postoperatively; monitoring for MRONJ continued at 21, 30, 60, and 90 days, and 6 months, followed by visits every 6 months | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Each patient was assigned by a computer‐randomization program to one of two groups." |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | High risk | Due to the nature of the intervention, the personnel and participants were not blinded. |
| Blinding of outcome assessment (detection bias) | High risk | At least during the mucosal healing period, due to the nature of the intervention, blinding of outcome assessors is not possible. |
| Incomplete outcome data (attrition bias) | Unclear risk | Completeness or loss to follow‐up was not reported. |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "All patients were prospectively examined before the start of therapy with zoledronic acid and were randomly allocated into two groups." Generation of randomisation sequence not reported |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "treatment was not possible to be blinded" |
| Blinding of outcome assessment (detection bias) | High risk | Not blinded |
| Incomplete outcome data (attrition bias) | High risk | High and unbalanced rate of cross‐overs: quote: "36 patients, who were randomized to participate in group B did not want to be part of a close follow‐up and were then regrouped in group A." "At the end of this study, 153 (93.3%) patients of group A and 79 (87.8%) patients from group B have died." Data analysis: as‐treated, not by intention‐to‐treat |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
All participants were given MRONJ stage‐appropriate conventional treatment plus intensive antibiotic therapy as needed. | |
| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "We randomly assigned the 13 patients" Generation of randomisation sequence not reported |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | High risk | Participants and personnel not blinded |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors not reported |
| Incomplete outcome data (attrition bias) | High risk | One participant did not complete the study and was excluded from the analysis. Quote: "weekly group, n = 7 including 2 patients with RA, with 1 later dropout" |
| Selective reporting (reporting bias) | High risk | Outcomes were reported but with inadequate detail for the data to be included in a meta‐analysis. Authors present P values of statistical analyses but do not report effect estimates of outcomes such as improvement of MRONJ. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions | Antibiotic therapy with '1g of third‐generation cephalosporin given intravenously twice daily, analgesics, daily irrigation using 0.12% chlorhexidine, and professional dental prophylaxis during 1 week before surgery' was performed in both groups.
After performing intravenous sedation or general anaesthesia with local anaesthesia on patients with MRONJ, surgeons used surgical curettes to remove bony sequestra and granulation until flesh bleeding from the bone was confirmed. Sharp bony margins were smoothened and an antibiotic solution (2g of third generation cephalosporin in 1L saline) was applied to remove debris and foreign bodies and to reduce bacterial contamination. Before primary closure of the mucoperiosteal flap, L‐PRF was added to the bone surface of patients in the L‐PRF group. In the PRF plus BMP group a collagen sponge section with rhBMP‐2 was placed first and then L‐PRF was placed to the bony margins. By using a rhBMP‐2 commercial kit with a 0.5 mL rhBMP‐2 solution and hydroxylapatite, rhBMP‐2 solution was gained and applied to a collagen sponge and then used in patients with MRONJ. All patients received intravenous antibiotics for 1 week postoperatively and oral antibiotics (third‐generation cephalosporin) for another 2 weeks. | |
| Outcomes |
Follow‐up examinations: mucosal healing was monitored weekly for the first month then monthly for 6 months. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Patients were randomly assigned" Method of random sequence generation not described |
| Allocation concealment (selection bias) | Unclear risk | Allocation concealment not reported |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel not reported. Due to the nature of the intervention, surgeons were not blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment not reported |
| Incomplete outcome data (attrition bias) | Low risk | No dropouts or exclusions from the analysis |
| Selective reporting (reporting bias) | High risk | Results were not reported for all follow‐up time points. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
Bisphosphonate or denosumab drug holiday prior to the tooth extraction was not required. All patients received perioperative intravenous antibiotic therapy (penicillin 10, 000,000 IU once daily or clindamycin 600 mg three times daily in case of penicillin allergy), initiated 1 day before surgery and continued until 1 day after surgery. Prior to the extraction, all patients rinsed their mouth with chlorhexidine solution. Postoperatively, patients were instructed to consume a soft diet, to apply daily mouth rinses with chlorhexidine solution, and to refrain from wearing dentures until complete mucosal healing was achieved. | |
| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Assignment to one of the two groups was performed via block randomization with randomly selected block sizes." The process of selecting the blocks, such as a random number table or a computer random number generator, was not specified. |
| Allocation concealment (selection bias) | Unclear risk | Allocation concealment not reported |
| Blinding of participants and personnel (performance bias) | High risk | Due to the nature of the intervention, blinding was not possible. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not reported. |
| Incomplete outcome data (attrition bias) | Low risk | No dropouts or exclusions from the analysis |
| Selective reporting (reporting bias) | Low risk | No selective reporting |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
In all participants, a tension‐free wound closure was achieved using mucoperiosteal flaps. All participants remained in hospital for 4 days after the operation. Participants received routine postoperative instructions and the same postoperative analgesic drug therapy. Antibiotic treatment involved the administration of ampicillin/sulbactam 2000 mg/1000 mg (or clindamycin in case of hypersensitivity to penicillin or a penicillin allergy) intravenously while in hospital and then orally for a further 6 days after discharge from the hospital. | |
| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Over a period of 12 months, the study population was prospectively referred for the treatment of MRONJ and divided randomly into two study groups" Generation of randomisation sequence not reported |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | High risk | Not blinded |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not reported |
| Incomplete outcome data (attrition bias) | Low risk | 4 participants (2 each in the TF and the AF group) died after T2 (8 weeks after the operation) and 2 participants in the AF group failed to attend the 1‐year follow‐up (T4). No participant was lost for assessment of the primary endpoint at T2 (8 weeks after the operation). |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions | All patients were pretreated with oral antibiotics from the week before surgery until one week after surgery. All patients used an antimicrobial mouth rinse with chlorhexidine three times daily, starting 2 days before surgery and for at least 5 days after surgery. If a "drug holiday" was possible from an oncologic/osteologic perspective, antiresorptive therapy was discontinued 1 month before surgery until 1 month after surgery.
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "An independent statistical consultant was employed to computer generate the randomization sequence via a centralized web‐based tool (www.randomizer.at) prior to the start of the study. This generated a pseudorandom code with permuted blocks of randomly variable size." |
| Allocation concealment (selection bias) | Low risk | Quote: "The sequence was known only to the programmer until the database lock. No one directly involved in the project had access to the allocation codes." Quote: "the allocation of the patients to the treatment groups was performed by the surgeons by means of sealed envelopes immediately before surgery." |
| Blinding of participants and personnel (performance bias) | High risk | Quote: "patients were not informed about their allocation" Surgeons were not blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "The physicians and research nurses who carried out the postoperative follow‐ups and assessed the outcomes and the statistician were all blinded to treatment allocation during the entire study." |
| Incomplete outcome data (attrition bias) | High risk | Several dropouts during follow‐up. 8 participants allocated to EPP did not receive allocated intervention but switched to SPP. |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions |
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Random assignment was performed in blocks and was stratified according to duration of MRONJ diagnosis: < 12 months or ≥ 12 months" The process of selecting the blocks, such as a random number table or a computer random number generator, was not specified. |
| Allocation concealment (selection bias) | Unclear risk | Concealment of allocation not reported |
| Blinding of participants and personnel (performance bias) | Low risk | Quote: "we conducted a prospective doubleblind, placebo‐controlled, randomized trial" |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "we conducted a prospective doubleblind, placebo‐controlled, randomized trial" |
| Incomplete outcome data (attrition bias) | High risk | In the placebo group, 1 participant was lost to follow‐up and 1 participant died during follow‐up. Quote: Quote: "All analyses were based on the intention‐to‐treat principle". Although 19 participants were assigned to the placebo group, only 18 placebo participants were included in analyses. |
| Selective reporting (reporting bias) | High risk | Not all outcomes were reported; for example, quality of life survey data were missing. |
| Study characteristics | ||
| Methods |
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| Participants |
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| Interventions | CGF, like platelet‐rich plasma or platelet‐rich fibrin, is an autologous preparation obtained from the patient's blood immediately before surgery. All participants underwent removal of necrotic bone and primary closure of the surgical site.
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| Outcomes |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of sequence generation not reported |
| Allocation concealment (selection bias) | Low risk | Quote: "The sequentially numbered sealed envelopes were used by the examiner (G.I.) to randomly assign patients to the study groups. Before the surgery, these sealed envelopes were opened by the same examiner, and each patient was assigned to one of the study groups." |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants were not reported. Surgeons were not blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Quote: "Preoperative and postoperative data were recorded by the blinded examiner (E.A.), who did not participate in randomization or surgical procedures." |
| Incomplete outcome data (attrition bias) | Low risk | The study was completed with all participants. |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the Methods were all reported. |
AAOMS: Association of Oral and Maxillofacial Surgeons; CT: computed tomography;eGFR: estimated glomerular filtration rate; EPP: epiperiosteal prepared; g: gram;IU: international unit; IV: intravenous; mg: milligram;MRONJ: medication‐related osteonecrosis of the jaw;PET: positron emission tomography; PRF: platelet‐rich fibrin;PRGF: plasma rich in growth factors; PTH: parathyroid hormone; RCT: randomised controlled trial; SPP: subperiosteal prepared; VAS: visual analogue scale; yr: year(s)
Characteristics of excluded studies [author‐defined order]
| Study | Reason for exclusion |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT | |
| Not a RCT |
RCT: randomised clinical trial
Characteristics of ongoing studies [ordered by study ID]
| Study name | Clinical study of modified curettage for medication‐related osteonecrosis of the jaw |
| Methods | Interventional, randomised, parallel trial |
| Participants |
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| Interventions | Control group: curettage Exprimental group: curettage plus bone tunnel preparation |
| Outcomes |
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| Starting date | |
| Contact information | Peking University Hospital of Stomotology, 22 Zhongguancun South Street, Haidian District, Beijing, China |
| Notes |
| Study name | Treatment strategies for medication‐related osteonecrosis of the jaw ‐ a prospective, partially randomized patient preference trial |
| Methods | Interventional, randomised, open, monocentre trial |
| Participants | Target sample size: 90 participants Both sexes eligible for study, 18 years and older Inclusion criteria
Exclusion criteria
|
| Interventions | Group 1
Group 2
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| Outcomes | Primary outcome
Secondary outcome
All secondary outcomes measured at 10‐14 days (T1), 30 days (T2), 8 weeks (T3), 3 months (T4), 6 months (T5), 1 year (T6) postoperatively |
| Starting date | Date of first enrolment: 28 May 2018 |
| Contact information | [email protected]‐heidelberg.de |
| Notes |
| Study name | Investigation of the preventive effects of antimicrobial penetrated collagen plug (TERUPLUG) for post‐extraction tooth socket for osteonecrosis of the jaw after tooth extraction in patients using high‐dose antiresorptive agent |
| Methods |
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| Participants |
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| Interventions | Intervention group: insert of antimicrobial (MINOCYCLINE) penetrated collagen plug (TERUPLUG) for post‐extraction tooth socket, close the wound, and remove sutures 1 week later Control group: insert of collagen plug (TERUPLUG) for post‐extraction tooth socket, close the wound, and remove sutures 1 week later |
| Outcomes |
|
| Starting date | Date of first enrolment 2 July 2020 |
| Contact information |
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| Notes |
| Study name | Assessment of platelet rich fibrin efficiency on healing delay and on jawbone osteochemonecrosis provoked by bisphosphonates (OCN/PRF) |
| Methods | Interventional, randomised, parallel assignment, open‐label |
| Participants | 270 participants are required to validate the expected objectives in this study All sexes eligible for study, 18 years and older Inclusion criteria
Exclusion criteria
|
| Interventions | Experimental: bone curettage + PRF insertion Control: bone curettage alone without PRF insertion |
| Outcomes | Primary outcome measures
Secondary outcome measures
|
| Starting date | September 2011 |
| Contact information | e.gerard@chr‐metz‐thionville.fr |
| Notes |
| Study name | Prospective randomized study: assessment of PRF efficacy in prevention of jaw osteonecrosis after tooth extraction (PRF) |
| Methods | Interventional; randomised; parallel assignment, blinded |
| Participants | Cohort of 100 participants: control group 50 participants and experimental 50 participants All sexes eligible for study; 50 years and older Inclusion criteria
Exclusion criteria
|
| Interventions | Experimental: tooth extraction and insertion of PRF (non‐traumatic tooth extraction with antibiotics (amoxicillin clavulanate combination). Insertion of PRF membrane in tooth‐extraction site) Control: no PRF (non‐traumatic extraction with antibiotic without PRF insertion) |
| Outcomes | Number of participants with jaw osteonecrosis after tooth extraction |
| Starting date | January 2014 |
| Contact information | |
| Notes |
| Study name | Pentoxifylline and Tocopherol (PENTO) in the treatment of Medication‐related Osteonecrosis of the Jaw (MRONJ) |
| Methods | Interventional, randomised, parallel, blinded |
| Participants | Target sample size: 100 participants All sexes eligible for study, 18 years and older Inclusion criteria
Exclusion criteria
|
| Interventions | Experimental:
Control:
|
| Outcomes | Primary outcome:
Secondary outcome:
Time frame for all primary and secondary outcomes are 0 months, 1 month, 3 months, 6 months, 9 months, 12 months |
| Starting date | April 1, 2018 |
| Contact information | |
| Notes | Jasjit Dillon, University of Washington |
| Study name | Use of topical phenytoin in bisphosphonate‐related osteonecrosis of the mandible |
| Methods | Interventional, randomised, parallel, blinded |
| Participants | Target sample size: 20 participants All sexes eligible for study, 18 years and older Inclusion criteria
Exclusion criteria
|
| Interventions | Experimental
Control
|
| Outcomes | Primary outcome
Secondray outcomes
|
| Starting date | September 1, 2012 |
| Contact information | Reza Tabrizi, Shiraz University of Medical Sciences |
| Notes |
| Study name | Plasma rich in growth factors for treatment of medication related osteonecrosis of the jaw |
| Methods | Interventional, randomised, parallel, blinded |
| Participants | Target sample size: 150 participants All sexes eligible for study, 18 years or older Inclusion criteria
Exclusion criteria
|
| Interventions | Experimental
Control
|
| Outcomes | Primary outcome
Secondary outcome
|
| Starting date | September 2018 |
| Contact information | Oreste Iocca, University of Roma La Sapienza |
| Notes |
| Study name | Best Treatment Choice for Osteonecrosis of the jaw (BETCON) |
| Methods | Multicentre, interventional, phase 4, randomised, parallel, open‐label trial |
| Participants | Target sample size: 125 participants All sexes eligible for study, 18 years or older Inclusion criteria
Exclusion criteria
|
| Interventions |
|
| Outcomes | Primary outcome
Secondary outcome
|
| Starting date | October 1, 2020 |
| Contact information | Tim Van den Wyngaert, University Hospital, Antwerp |
| Notes |
| Study name | Surgical management of medication related osteonecrosis of the jaws with concentrated growth factor |
| Methods | Interventional, randomised |
| Participants | 28 female participants; 65 to 85 years Inclusion criteria
Exclusion criteria
|
| Interventions | Concentrated Growth Factor (CGF) + primarily closure vs no CGF + primarily closure |
| Outcomes | Soft tissue healing 6 months postoperatively |
| Starting date | May 1, 2016 |
| Contact information | Principal Investigator: Gözde Işık, Lecturer, Ege University, Izmir, Turkey |
| Notes |
| Study name | Study to the effect of teriparatide formulation Forteo versus Teribone on bisphosphonate‐related osteonecrosis of the jaw in osteoporosis patients |
| Methods | Interventional, parallel, randomised, open study |
| Participants | Target sample size: 15 female participants >= 20 years of age Inclusion criteria
Exclusion criteria
|
| Interventions | Forteo (teriparatide) vs Teribone (teriparatide) |
| Outcomes |
|
| Starting date | August 2012 |
| Contact information | [email protected]‐u.ac.jp |
| Notes |
| Study name | The clinical effect of teriparatide on BRONJ (bisphosphonate‐related osteonecrosis of the jaw) |
| Methods | Interventional, parallel, randomised, open study |
| Participants | Target sample size: 20 participants All sexes eligible for study, 20 years or older Inclusion criteria
Exclusion criteria
|
| Interventions |
|
| Outcomes | Primary Outcome
|
| Starting date | 2012/01/01 |
| Contact information | Daigo Yoshiga, Kyshu Dental University Oral Medicine [email protected]‐dent.ac.jp |
| Notes |
AAOMS: Association of Oral and Maxillofacial Surgeons; LPRF: leukocyte and platelet‐rich fibrin; MRONJ: medication‐related osteonecrosis of the jaw;OCN: osteochemonecrosis; PRF: platelet‐rich fibrin.
1. P1NP, N‐terminal propeptide of type 1 collagen Procollagen I Intact N‐Terminal
2. Beta‐CTX, Beta‐carboxy‐terminal telopeptide of type 1 collagen (beta‐CrossLaps)
3. Cicatrisation: formation of scar tissue at a wound site by fibroblasts
Data and analyses
| 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] |
| Analysis 1.1  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) | ||||
| 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] | |
| Analysis 1.2  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) | ||||
| 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] |
| Analysis 2.1  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) | ||||
| 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] |
| Analysis 3.1  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 | ||||
| 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] |
| Analysis 4.1  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 | ||||
| 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] |
| Analysis 5.1  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 | ||||
| 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] |
| Analysis 6.1  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 | ||||
| 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] |
| Analysis 7.1  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 | ||||
| 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] |
| Analysis 8.1  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 | ||||
| 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] |
| Analysis 8.2  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 | ||||
| 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] |
| Analysis 9.1  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 | ||||
| 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] |
| Analysis 10.1  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 | ||||
| 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] |
| Analysis 11.1  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 | ||||
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] |
