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Study flow diagram. Results of the search strategy for inclusion of studies in this review
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Figure 1

Study flow diagram. Results of the search strategy for inclusion of studies in this review

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'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
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Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

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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).
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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).

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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).
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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).

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Comparison 2 A dental extraction protocol with plasma rich in growth factors (PRGF) (experimental) versus a standard dental extraction protocol without PRGF (control) for prophylaxis of MRONJ in people treated with IV bisphosphonates who need dental extractions, Outcome 1 MRONJ (incidence proportion).
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Analysis 2.1

Comparison 2 A dental extraction protocol with plasma rich in growth factors (PRGF) (experimental) versus a standard dental extraction protocol without PRGF (control) for prophylaxis of MRONJ in people treated with IV bisphosphonates who need dental extractions, Outcome 1 MRONJ (incidence proportion).

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Comparison 3 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.
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Analysis 3.1

Comparison 3 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.

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Comparison 4 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.
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Analysis 4.1

Comparison 4 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.

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Summary of findings for the main comparison. Dental examinations at three‐month intervals and preventive treatments (experimental) compared to standard care (control) for prophylaxis of MRONJ

Dental examinations at three‐month intervals and preventive treatments (experimental) compared to standard care (control) for prophylaxis of MRONJ

Population: prophylaxis of MRONJ
Setting: hospital
Intervention: dental examinations at three‐month intervals and preventive treatments (experimental)
Comparison: standard care (control)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with standard care (control)

Risk with dental examinations at three‐month intervals and preventive treatments (experimental)

MRONJ (incidence proportion)
Diagnostic criteria for MRONJ: non‐healing exposed bone in mandible or maxilla for longer than 8 weeks without any change of the stage of disease

(follow‐up: mean 32 months)

233 per 1000

23 per 1000
(5 to 91)

RR 0.10
(0.02 to 0.39)

253
(1 RCT)

⊕⊕⊝⊝
LOW1

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).
CI: confidence interval; RR: risk ratio; OR: odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. We downgraded the quality of the evidence by two levels due to very serious risk of bias (high and unbalanced rate of crossovers after randomisation, high drop‐out rates due to high mortality, failure to adhere to the intention‐to‐treat principle, the mean follow‐up differed between experimental and control group).

MRONJ = medication‐related osteonecrosis of the jaw

RCT = randomised controlled trial
Figuras y tablas -
Summary of findings for the main comparison. Dental examinations at three‐month intervals and preventive treatments (experimental) compared to standard care (control) for prophylaxis of MRONJ
Ir a la tabla de la revisión
Summary of findings 2. A 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

A 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
Setting: hospital
Intervention: a dental extraction protocol with PRGF (experimental)
Comparison: a standard dental extraction protocol without PRGF (control)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with a standard dental extraction protocol without PRGF (control)

Risk with a dental extraction protocol with PRGF (experimental)

MRONJ (incidence proportion)
Diagnostic criteria of MRONJ: pain, swelling, and non‐healing exposed necrotic bone or fistulae, or both, with connection to the bone
(follow‐up: 24‐60 months)

59 per 1000

5 per 1000
(0 to 89)

RR 0.08
(0.00 to 1.51)

176
(1 RCT)

⊕⊝⊝⊝
VERY LOW1

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).
CI: confidence interval; RR: risk ratio; OR: odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. We downgraded the quality of the 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).

IV = intravenous

MRONJ = medication‐related osteonecrosis of the jaw

RCT = randomised controlled trial
Figuras y tablas -
Summary of findings 2. A 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
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Summary of findings 3. Hyperbaric oxygen therapy as an adjunct to conventional therapy (experimental) compared to conventional therapy (control) for treatment of MRONJ

Hyperbaric oxygen therapy as an adjunct to conventional therapy (experimental) compared to conventional therapy (control) for treatment of MRONJ

Population: treatment of MRONJ
Setting: hospital
Intervention: hyperbaric oxygen therapy as an adjunct to conventional therapy (experimental)
Comparison: conventional therapy (control)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with conventional therapy (control)

Risk with hyperbaric oxygen therapy as an adjunct to conventional therapy (experimental)

Healing of MRONJ
Diagnostic criteria for healing of MRONJ: gingival coverage with no exposed bone

(follow‐up: up to 24 months (outcome was measured at last follow‐up))

333 per 1000

520 per 1000
(257 to 1000)

RR 1.56
(0.77 to 3.18)

46 participants included in the analysis
(1 RCT)

⊕⊝⊝⊝
VERY LOW1

*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).
CI: confidence interval; RR: risk ratio; OR: odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. We downgraded the quality 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).

MRONJ = medication‐related osteonecrosis of the jaw

RCT = randomised controlled trial
Figuras y tablas -
Summary of findings 3. Hyperbaric oxygen therapy as an adjunct to conventional therapy (experimental) compared to conventional therapy (control) for treatment of MRONJ
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Summary of findings 4. Autofluorescence‐guided bone surgery (experimental) compared to tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ

Autofluorescence‐guided bone surgery (experimental) compared to tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ

Population: treatment of MRONJ
Setting: hospital
Intervention: autofluorescence‐guided bone surgery (experimental)
Comparison: tetracycline fluorescence‐guided bone surgery (control)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with tetracycline fluorescence‐guided bone surgery (control)

Risk with autofluorescence‐guided bone surgery (experimental)

Healing of MRONJ
Criteria for healing of MRONJ: mucosal integrity

(follow‐up: 1 year)

889 per 1000

933 per 1000
(764 to 1000)

RR 1.05
(0.86 to 1.30)

34 participants included in the analysis
(1 RCT)

⊕⊝⊝⊝
VERY LOW1

*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).
CI: confidence interval; RR: risk ratio; OR: odds ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. We downgraded the quality 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).

MRONJ = medication‐related osteonecrosis of the jaw

RCT = randomised controlled trial
Figuras y tablas -
Summary of findings 4. Autofluorescence‐guided bone surgery (experimental) compared to tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ
Ir a la tabla de la revisión
Table 1. Clinical staging of MRONJ

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)

Figuras y tablas -
Table 1. Clinical staging of MRONJ
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Comparison 1. Dental examinations at three‐month intervals and preventive treatments (experimental) versus standard care (control) for prophylaxis of MRONJ

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 MRONJ (incidence proportion) Show forest plot

1

253

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.02, 0.39]

2 MRONJ (incidence rate: MRONJ cases per patient‐year) Show forest plot

1

Rate ratio (Fixed, 95% CI)

0.18 [0.04, 0.74]
Figuras y tablas -
Comparison 1. Dental examinations at three‐month intervals and preventive treatments (experimental) versus standard care (control) for prophylaxis of MRONJ
Ir a la tabla de la revisión
Comparison 2. A dental extraction protocol with plasma rich in growth factors (PRGF) (experimental) versus a standard dental extraction protocol without PRGF (control) for prophylaxis of MRONJ in people treated with IV bisphosphonates who need dental extractions

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 MRONJ (incidence proportion) Show forest plot

1

176

Risk Ratio (M‐H, Random, 95% CI)

0.08 [0.00, 1.51]
Figuras y tablas -
Comparison 2. A dental extraction protocol with plasma rich in growth factors (PRGF) (experimental) versus a standard dental extraction protocol without PRGF (control) for prophylaxis of MRONJ in people treated with IV bisphosphonates who need dental extractions
Ir a la tabla de la revisión
Comparison 3. Hyperbaric oxygen as an adjunct to conventional therapy (experimental) versus conventional therapy (control) for treatment of MRONJ

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

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]
Figuras y tablas -
Comparison 3. Hyperbaric oxygen as an adjunct to conventional therapy (experimental) versus conventional therapy (control) for treatment of MRONJ
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Comparison 4. Autofluorescence‐guided bone surgery (experimental) versus tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

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]
Figuras y tablas -
Comparison 4. Autofluorescence‐guided bone surgery (experimental) versus tetracycline fluorescence‐guided bone surgery (control) for treatment of MRONJ
Ir a la tabla de la revisión