Non-Cochrane · aetiology · PM41975407
Serum vitamin D Levels in patients with medication-related osteonecrosis of the jaw: a systematic review and meta-analysis.
Daneshvar Alireza, Daneshvar Kimia, Musaie Farhan, et al. · BMC oral health · 2026 · PubMed · doi:10.1186/s12903-026-08303-9
Findings
23 findings
| Population | ||||
|---|---|---|---|---|
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Mean age (control group) | Meta-regression coefficient (B) 0.0660 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Control group sample size | Meta-regression coefficient (B) 0.0352 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Sensitivity: excluding Shirani et al. 2021 | SMD 0.09 [-0.31, 0.49] GRADE not reported 5 studies · 339 participants |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania | SMD -0.06 [-0.51, 0.39] Very low Downgraded: risk of bias, imprecision, inconsistency 6 studies · 359 participants |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Tooth extractions (MRONJ group) | Meta-regression coefficient (B) 0.6677 GRADE not reported 3 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Sensitivity: excluding Shirani et al. 2021 and Thumbigere-Math et al. 2016 | SMD -0.11 [-0.36, 0.15] GRADE not reported 4 studies · 266 participants |
| Adults (>=18 years) previously exposed to antiresorptive therapy (bisphosphonates and/or denosumab) | Presence of medication-related osteonecrosis of the jaw (MRONJ cases) | Antiresorptive-exposed individuals without MRONJ (controls) | Serum 25-hydroxyvitamin D [25(OH)D] level (standardized mean difference) Post-diagnosis · Leave-one-out sensitivity analysis: omitting Heim et al. 2017 | SMD -0.09 [-0.64, 0.46] GRADE not reported 5 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Descriptive pooled group mean: Control group | Pooled mean (ng/mL) 36.86 GRADE not reported 6 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Exclusively oncologic population | SMD 0.40 [-0.37, 1.16] GRADE not reported 2 studies · 136 participants |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Mean age (MRONJ group) | Meta-regression coefficient (B) -0.0078 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Latitude | Meta-regression coefficient (B) 0.0214 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Bisphosphonate duration (control group) | Meta-regression coefficient (B) 0.0196 GRADE not reported 3 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: % female (MRONJ group) | Meta-regression coefficient (B) -0.4270 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: % female (control group) | Meta-regression coefficient (B) -1.2602 GRADE not reported Studies not reported |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Mixed (osteoporotic plus oncologic) population | SMD -0.13 [-0.47, 0.21] GRADE not reported 3 studies · 203 participants |
| Adults (>=18 years) previously exposed to antiresorptive therapy (bisphosphonates and/or denosumab) | Presence of medication-related osteonecrosis of the jaw (MRONJ cases) | Antiresorptive-exposed individuals without MRONJ (controls) | Serum 25-hydroxyvitamin D [25(OH)D] level (standardized mean difference) Post-diagnosis · Leave-one-out sensitivity analysis: omitting Picardo et al. 2020 | SMD 0.02 [-0.48, 0.52] GRADE not reported 5 studies |
| Adults (>=18 years) previously exposed to antiresorptive therapy (bisphosphonates and/or denosumab) | Presence of medication-related osteonecrosis of the jaw (MRONJ cases) | Antiresorptive-exposed individuals without MRONJ (controls) | Serum 25-hydroxyvitamin D [25(OH)D] level (standardized mean difference) Post-diagnosis · Leave-one-out sensitivity analysis: omitting Park et al. 2022 | SMD -0.11 [-0.66, 0.44] GRADE not reported 5 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Tooth extractions (control group) | Meta-regression coefficient (B) -0.3946 GRADE not reported 3 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Sensitivity: excluding Thumbigere-Math et al. 2016 | SMD -0.21 [-0.57, 0.14] GRADE not reported 5 studies · 286 participants |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Descriptive pooled group mean: MRONJ group | Pooled mean (ng/mL) 33.16 GRADE not reported 6 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: Bisphosphonate duration (MRONJ group) | Meta-regression coefficient (B) -0.0592 GRADE not reported 3 studies |
| Adults (>=18 years) previously exposed to antiresorptive therapy (bisphosphonates and/or denosumab) | Presence of medication-related osteonecrosis of the jaw (MRONJ cases) | Antiresorptive-exposed individuals without MRONJ (controls) | Serum 25-hydroxyvitamin D [25(OH)D] level (standardized mean difference) Post-diagnosis · Leave-one-out sensitivity analysis: omitting Tsao et al. 2013 | SMD -0.09 [-0.64, 0.47] GRADE not reported 5 studies |
| Adults exposed to antiresorptives (bisphosphonates and/or denosumab) with MRONJ | Presence of MRONJ (exposure) | Antiresorptive-exposed individuals without MRONJ | Serum 25-hydroxyvitamin D [25(OH)D] level Post-diagnosis (single prespecified time point per study) · Hospital and clinical settings in Asia, the Americas, Europe and Oceania · Univariable random-effects meta-regression: MRONJ group sample size | Meta-regression coefficient (B) 0.0006 GRADE not reported Studies not reported |
Included primary studies 6
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Heim 2017 Vitamin D (25-OHD) deficiency may increase the prevalence of medication-related osteonecrosis of the jaw. PMID:29102331 | 2017 | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
| Park 2022 Serum biomarkers for bisphosphonate-related osteonecrosis of the jaw: a prospective clinical study. PMID:34471956 | 2022 | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
| Picardo 2020 DOI:10.31031/gjem.2020.03.000561 | NR | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
| Shirani 2021 Genesis of arrhythmias in the failing heart and therapeutic implications. PMID:2021115 | 1991 | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
| Thumbigere-Math 2016 Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of… PMID:26501428 | 2016 | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
| Tsao 2013 Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. PMID:23582590 | 2013 | this review only | Serum 25-hydroxyvitamin D [25(OH)D] level | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Adults (>=18 years) with prior exposure to antiresorptive therapies (bisphosphonates and/or denosumab) for any clinical indication | Adults exposed to bisphosphonates or denosumab: 184 MRONJ cases and 175 controls (n=359); mixed osteoporosis plus oncologic (3 studies) and exclusively oncologic (2 studies); one study with indication not reported |
| Intervention | Exposure: presence of MRONJ diagnosed using explicit clinical and/or radiographic criteria | MRONJ cases (n=184); bisphosphonates (oral/IV) and denosumab (one study) |
| Comparison | Antiresorptive-exposed individuals without MRONJ | Antiresorptive-exposed controls without MRONJ (n=175) |
| Outcomes | Serum 25-hydroxyvitamin D [25(OH)D] levels (mean and SD) in cases and controls | Serum 25(OH)D standardized mean difference (6 studies); pooled mean 33.16 ng/mL in MRONJ vs 36.86 ng/mL in controls |
| Study designs | Observational studies with an MRONJ case group and an antiresorptive-exposed non-MRONJ comparator group (case-control, cohort) | Six studies: five case-control and one prospective cohort |
| Timing | Post-diagnosis serum 25(OH)D; when several time points were reported, the earliest post-diagnosis assessment closest to diagnosis | Post-diagnosis sampling (one cohort also sampled at baseline and 4 months after diagnosis; earliest post-diagnosis time point used) |