RARE DISEASE
Osteonecrosis of the jaw
Osteonecrosis of the jaw
Osteonecrosis of the jaw
Drug discovery
1
drug
With orphan designation
Overview
Osteonecrosis of the jaw (ONJ) is a rare but serious condition characterized by exposed, non-healing jawbone due to impaired vascular supply, often associated with antiresorptive (bisphosphonates, denosumab) or antiangiogenic therapies. It typically manifests as pain, exposed bone (>8 weeks), and infection, with highest incidence in oncology patients receiving high-dose IV therapy. Management involves staged approaches, emphasizing early diagnosis and multidisciplinary care to prevent progression [1][3][9][14].
Burden
Significantly impacts quality of life, causing chronic pain, dysphagia, and disfigurement [9][14].
Incidence rises with prolonged antiresorptive use: ~1% at 1 year, 3% at 3 years in cancer patients [10], reaching 9% in metastatic breast cancer cohorts [14].
Treatment costs and morbidity escalate in advanced stages due to complex surgical needs and prolonged antimicrobial therapy [4][7][12].
Therapies
Conservative: Antibiotics (e.g., penicillin, clindamycin), chlorhexidine rinses, and analgesia for early stages (0–2) [8][12][15].
Surgical: Debridement or resection for advanced non-responsive cases (stage 3), often combined with platelet-rich fibrin or laser therapy [7][16].
Preventive: Pre-therapy dental evaluation, minimally invasive procedures (e.g., root canals over extractions), and smoking cessation [1][5][9].
Categories: rare bone diseases, rare systemic and rheumatological diseases
Research Papers
2,056 drug discovery papers about Osteonecrosis of the jaw, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,056 drug discovery papers about Osteonecrosis of the jaw, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-09 | Individualized 3D-Printed Titanium Mesh-Assisted Alveolar Reconstruction and Implant Rehabilitation Following MRONJ Resection: A Case Report.
Medication-related osteonecrosis of the jaw is a severe complication of antiresorptive therapy that often necessitates complex reconstructive surgery. This report describes a case of implant-supported rehabilitation using a customized 3D-printed titanium mesh for an extensive mandibular defect resulting from medication-related osteonecrosis of the jaw. A 58-year-old woman with stage-3 medication-related osteonecrosis of the jaw after zoledronate therapy underwent segmental mandibulectomy and reconstruction with a free iliac crest graft. Nine months later, a customized titanium mesh was placed to protect the planned 9.5-11 mm augmentation. Cone beam computed tomography confirmed mineralized regeneration within the mesh. The mesh was removed after achieving 9.5 mm vertical and 11 mm horizontal alveolar augmentation, and 4 implants were placed with high primary stability (insertion torque ≥ 40 N cm). At 6 months, resonance frequency analysis values ranged from 75 to 84, allowing delivery of a splinted fixed prosthesis. At 12 months of loading, the peri-implant tissues remained normal with stable radiographic bone levels and satisfactory function. Combining customized 3D-printed titanium mesh with guided implant placement supports stable bone regeneration and prosthetic rehabilitation in patients with medication-related osteonecrosis of the jaw. However, outcomes depend on medication history, therapy timing, and unresolved drug-related factors, underscoring the need for a multidisciplinary approach with individualized treatment and proactive complication care.
2026-07-31 | [A retrospective study of pedicled flaps for repair of oral mucosal defects in patients with medication-related osteonecrosis of the jaw].
Objective: To investigate the clinical efficacy of pedicled flaps for repairing oral mucosa defects in medication-related osteonecrosis of the jaw (MRONJ), and to analyze the indications for different types of pedicled flaps. Methods: The clinical data of 158 MRONJ patients who met the inclusion criteria and were admitted to the Department of Maxillofacial Trauma and Orthognathic Surgery, Hospital of Stomatology, Air Force Medical University from January 2019 to December 2024 were retrospectively analyzed, including 74 males (46.8%) and 84 females (53.2%).The mean age was (59.2±10.7) years (range, from 20 to 87 years old). According to the method of soft tissue repair, the patients were divided into direct suture group (61 cases) and pedicled tissue flap group (97 cases, including 80 cases of buccal fat pad flap and 17 cases of submental island flap). The rate of secondary operation was compared between the two groups. Multivariate binary Logistic regression and subgroup analysis were used to evaluate the efficacy and influencing factors of pedicled tissue flaps, and the comparison between the buccal fat pad flap and submental island flap was performed. Results: The median follow-up time was 36 months. Univariate analysis showed that the secondary operation rate was 68.9% (42/61) in the direct suture group, which was significantly higher than 16.5% (16/97) in the pedicled tissue flap group (P<0.001). After adjusting for confounding factors such as age and lesion location, multivariate Logistic regression analysis showed that pedicled tissue flap was an independent protective factor against the risk of secondary surgery (OR=0.049, P<0.001). Stage 3 disease was an independent risk factor for secondary surgery (OR=8.455, P=0.002). Subgroup analysis showed that the secondary operation rate of pedicled tissue flap was significantly lower than that of direct suture in stage 3 group, mandibular group,<65 years group, male group and female group (all P<0.05). There was no significant difference among stage 2 group, maxillary group and≥65 years group (all P>0.05), but the trend of protection was the same. The secondary operation rate was 17.5% (14/80) in the buccal fat pad flap group and 2/17 in the submental island flap group. There was no significant difference between the two groups (P=0.730). Conclusions: The use of pedicled tissue flap for repairing oral mucosal wounds can significantly reduce the risk of secondary surgery for MRONJ, and the effect is superior to direct suture. Buccal fat pad flap is the first choice for maxillary and retromolar mucosal defects, and submental island flap can be used for large mandibular mucosal defects.
2026-07-31 | [Role and mechanism of methyltransferase-like 3 in promoting macrophage NLRP3 inflammatory responses in medication-related osteonecrosis of the jaw].
Objective: To investigate the role and mechanism of methyltransferase-like 3 (METTL3) in regulating macrophage inflammatory responses and the derelopment of medication-related osteonecrosis of the jaw (MRONJ) at the single-cell level. Methods: Single-cell RNA sequencing was used to construct an immune atlas of zoledronic acid (ZA)-induced bisphosphonate-related osteonecrosis of the jaw(BRONJ)-like lesions in mice. Key epigenetic regulators were screened by bioinformatic analysis, and key genes were predicted using virtual knockdown analysis. METTL3 expression in vivo and in vitro was validated by immunohistochemical staining and Western blotting. In vitro knockdown and overexpression experiments were performed to clarify the regulatory effect of METTL3 on NLRP3 inflammasome activation in macrophages. Results: The single-cell atlas showed that ZA treatment significantly induced the recruitment of specific pro-inflammatory macrophage subsets in extraction sockets, accompanied by marked activation of inflammation-related pathways. Bioinformatic screening indicated that NLRP3 inflammasome-related genes served as a central bridge linking inflammatory responses to RNA processing and modification. Pseudotime trajectory and virtual knockdown analyses further suggested that METTL3 functioned as a key node in maintaining the pro-inflammatory state of macrophages. In vivo and in vitro experiments confirmed that ZA significantly induced METTL3 upregulation at both tissue and cellular levels, accompanied by an increase in global m6A levels. Functional assays showed that METTL3 knockdown markedly suppressed NLRP3 inflammasome activation, whereas METTL3 overexpression exerted the opposite effect. Conclusions: This study reveals the critical role of METTL3 as a positive regulator in promoting macrophage NLRP3 inflammatory responses in MRONJ pathogenesis. METTL3 is expected to provide clues for targeted therapy research on modulating local immune dysregulation and promoting bone repair in MRONJ.
2026-07-31 | [Research progress of mesenchymal stem cells in the treatment of medication-related osteonecrosis of the jaw].
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication characterized primarily by jawbone necrosis, induced by bisphosphonates or other targeted agents for systemic diseases. With the advancement of systemic anticancer therapies, the survival of patients with advanced malignancies has been prolonged, leading to an annual increase in the number of patients with MRONJ. However, there is currently no effective treatment for MRONJ worldwide. Recent studies have indicated that mesenchymal stem cells exhibit significant potential for osteogenic and angiogenic differentiation, proliferation, immunomodulation, and anti-inflammatory effects, thereby providing a novel therapeutic strategy for medication-related osteonecrosis of the jaw. This article reviews the research on mesenchymal stem cell therapy for MRONJ, providing a reference for its clinical research and treatment.
2026-07-29 | Should Teriparatide Be Part of Our Clinical Armamentarium in the Management of Medication-Related Osteonecrosis of the Jaw? A Systematic Review and Meta-Analysis.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe and potentially debilitating drug reaction. Adjunctive treatments including pentoxifylline, tocopherol, and teriparatide (TPTD) have been studied, but TPTD's efficacy remains unclear. This systematic review and meta-analysis aims to consolidate and evaluate high-quality evidence on TPTD in managing MRONJ. An electronic search strategy was performed on 3 databases (Pubmed, Embase, and Cochrane CENTRAL). Search terms include ("Teriparatide" OR "TPTD" OR "Recombinant Parathyroid Hormone" OR "Recombinant PTH") AND ("Medication-Related Osteonecrosis of the Jaw" OR "MRONJ" OR "BRONJ"). No publication date range was utilized. Inclusion criteria include randomized controlled trials, case-control studies, and cohort studies. All systematic reviews, case reports, case series, animal studies, editorials, non-English publications, or studies relating to osteoradionecrosis were excluded. Each study was screened independently, followed by final study selection after discussion with all authors. Primary meta-analysis used Cox proportional hazards regression with pseudo-individual-subject data reconstructed from published Kaplan-Meier curves (Guyot method) and a Tierney events + P value derivation for one study without Kaplan-Meier data. A sensitivity analysis pooled odds ratios (ORs) at the 6-month clinical response endpoint. Primary outcomes include improvement in MRONJ clinical staging. Secondary outcomes include time to improvement, adverse effects, radiographic evaluation, and presence of serum markers. After review of 162 studies, 5 (3.1%) studies were included in the systematic review with 3 (1.9%) studies included in the meta-analysis (n = 101 subjects). A three-study Cox hazard ratio (HR) meta-analysis yielded a pooled HR of 5.35 (95% CI, 3.14 to 9.13, P < .0001, I2 = 0%) favoring TPTD. Subgroup analyses by dosing regimen showed directionally consistent effects (daily pooled HR = 12.52; 95% CI, 5.75 to 27.23; weekly pooled HR = 8.09; 95% CI, 3.59 to 18.26; both I2 = 0%), and an OR-based sensitivity analysis at the 6-month binary healing endpoint was directionally concordant (pooled OR = 14.26; 95% CI, 2.83 to 71.77). Adjunctive TPTD shows improvement of MRONJ staging and time to healing compared to conventional treatments alone, but the magnitude of the impact remains unclear. Additional evidence, including studies evaluating dosing regimens and subject segmentation by MRONJ staging, is warranted.
2026-08-09 | Individualized 3D-Printed Titanium Mesh-Assisted Alveolar Reconstruction and Implant Rehabilitation Following MRONJ Resection: A Case Report.
Medication-related osteonecrosis of the jaw is a severe complication of antiresorptive therapy that often necessitates complex reconstructive surgery. This report describes a case of implant-supported rehabilitation using a customized 3D-printed titanium mesh for an extensive mandibular defect resulting from medication-related osteonecrosis of the jaw. A 58-year-old woman with stage-3 medication-related osteonecrosis of the jaw after zoledronate therapy underwent segmental mandibulectomy and reconstruction with a free iliac crest graft. Nine months later, a customized titanium mesh was placed to protect the planned 9.5-11 mm augmentation. Cone beam computed tomography confirmed mineralized regeneration within the mesh. The mesh was removed after achieving 9.5 mm vertical and 11 mm horizontal alveolar augmentation, and 4 implants were placed with high primary stability (insertion torque ≥ 40 N cm). At 6 months, resonance frequency analysis values ranged from 75 to 84, allowing delivery of a splinted fixed prosthesis. At 12 months of loading, the peri-implant tissues remained normal with stable radiographic bone levels and satisfactory function. Combining customized 3D-printed titanium mesh with guided implant placement supports stable bone regeneration and prosthetic rehabilitation in patients with medication-related osteonecrosis of the jaw. However, outcomes depend on medication history, therapy timing, and unresolved drug-related factors, underscoring the need for a multidisciplinary approach with individualized treatment and proactive complication care.
2026-07-31 | [A retrospective study of pedicled flaps for repair of oral mucosal defects in patients with medication-related osteonecrosis of the jaw].
Objective: To investigate the clinical efficacy of pedicled flaps for repairing oral mucosa defects in medication-related osteonecrosis of the jaw (MRONJ), and to analyze the indications for different types of pedicled flaps. Methods: The clinical data of 158 MRONJ patients who met the inclusion criteria and were admitted to the Department of Maxillofacial Trauma and Orthognathic Surgery, Hospital of Stomatology, Air Force Medical University from January 2019 to December 2024 were retrospectively analyzed, including 74 males (46.8%) and 84 females (53.2%).The mean age was (59.2±10.7) years (range, from 20 to 87 years old). According to the method of soft tissue repair, the patients were divided into direct suture group (61 cases) and pedicled tissue flap group (97 cases, including 80 cases of buccal fat pad flap and 17 cases of submental island flap). The rate of secondary operation was compared between the two groups. Multivariate binary Logistic regression and subgroup analysis were used to evaluate the efficacy and influencing factors of pedicled tissue flaps, and the comparison between the buccal fat pad flap and submental island flap was performed. Results: The median follow-up time was 36 months. Univariate analysis showed that the secondary operation rate was 68.9% (42/61) in the direct suture group, which was significantly higher than 16.5% (16/97) in the pedicled tissue flap group (P<0.001). After adjusting for confounding factors such as age and lesion location, multivariate Logistic regression analysis showed that pedicled tissue flap was an independent protective factor against the risk of secondary surgery (OR=0.049, P<0.001). Stage 3 disease was an independent risk factor for secondary surgery (OR=8.455, P=0.002). Subgroup analysis showed that the secondary operation rate of pedicled tissue flap was significantly lower than that of direct suture in stage 3 group, mandibular group,<65 years group, male group and female group (all P<0.05). There was no significant difference among stage 2 group, maxillary group and≥65 years group (all P>0.05), but the trend of protection was the same. The secondary operation rate was 17.5% (14/80) in the buccal fat pad flap group and 2/17 in the submental island flap group. There was no significant difference between the two groups (P=0.730). Conclusions: The use of pedicled tissue flap for repairing oral mucosal wounds can significantly reduce the risk of secondary surgery for MRONJ, and the effect is superior to direct suture. Buccal fat pad flap is the first choice for maxillary and retromolar mucosal defects, and submental island flap can be used for large mandibular mucosal defects.
2026-07-31 | [Role and mechanism of methyltransferase-like 3 in promoting macrophage NLRP3 inflammatory responses in medication-related osteonecrosis of the jaw].
Objective: To investigate the role and mechanism of methyltransferase-like 3 (METTL3) in regulating macrophage inflammatory responses and the derelopment of medication-related osteonecrosis of the jaw (MRONJ) at the single-cell level. Methods: Single-cell RNA sequencing was used to construct an immune atlas of zoledronic acid (ZA)-induced bisphosphonate-related osteonecrosis of the jaw(BRONJ)-like lesions in mice. Key epigenetic regulators were screened by bioinformatic analysis, and key genes were predicted using virtual knockdown analysis. METTL3 expression in vivo and in vitro was validated by immunohistochemical staining and Western blotting. In vitro knockdown and overexpression experiments were performed to clarify the regulatory effect of METTL3 on NLRP3 inflammasome activation in macrophages. Results: The single-cell atlas showed that ZA treatment significantly induced the recruitment of specific pro-inflammatory macrophage subsets in extraction sockets, accompanied by marked activation of inflammation-related pathways. Bioinformatic screening indicated that NLRP3 inflammasome-related genes served as a central bridge linking inflammatory responses to RNA processing and modification. Pseudotime trajectory and virtual knockdown analyses further suggested that METTL3 functioned as a key node in maintaining the pro-inflammatory state of macrophages. In vivo and in vitro experiments confirmed that ZA significantly induced METTL3 upregulation at both tissue and cellular levels, accompanied by an increase in global m6A levels. Functional assays showed that METTL3 knockdown markedly suppressed NLRP3 inflammasome activation, whereas METTL3 overexpression exerted the opposite effect. Conclusions: This study reveals the critical role of METTL3 as a positive regulator in promoting macrophage NLRP3 inflammatory responses in MRONJ pathogenesis. METTL3 is expected to provide clues for targeted therapy research on modulating local immune dysregulation and promoting bone repair in MRONJ.
2026-07-31 | [Research progress of mesenchymal stem cells in the treatment of medication-related osteonecrosis of the jaw].
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication characterized primarily by jawbone necrosis, induced by bisphosphonates or other targeted agents for systemic diseases. With the advancement of systemic anticancer therapies, the survival of patients with advanced malignancies has been prolonged, leading to an annual increase in the number of patients with MRONJ. However, there is currently no effective treatment for MRONJ worldwide. Recent studies have indicated that mesenchymal stem cells exhibit significant potential for osteogenic and angiogenic differentiation, proliferation, immunomodulation, and anti-inflammatory effects, thereby providing a novel therapeutic strategy for medication-related osteonecrosis of the jaw. This article reviews the research on mesenchymal stem cell therapy for MRONJ, providing a reference for its clinical research and treatment.
2026-07-29 | Should Teriparatide Be Part of Our Clinical Armamentarium in the Management of Medication-Related Osteonecrosis of the Jaw? A Systematic Review and Meta-Analysis.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe and potentially debilitating drug reaction. Adjunctive treatments including pentoxifylline, tocopherol, and teriparatide (TPTD) have been studied, but TPTD's efficacy remains unclear. This systematic review and meta-analysis aims to consolidate and evaluate high-quality evidence on TPTD in managing MRONJ. An electronic search strategy was performed on 3 databases (Pubmed, Embase, and Cochrane CENTRAL). Search terms include ("Teriparatide" OR "TPTD" OR "Recombinant Parathyroid Hormone" OR "Recombinant PTH") AND ("Medication-Related Osteonecrosis of the Jaw" OR "MRONJ" OR "BRONJ"). No publication date range was utilized. Inclusion criteria include randomized controlled trials, case-control studies, and cohort studies. All systematic reviews, case reports, case series, animal studies, editorials, non-English publications, or studies relating to osteoradionecrosis were excluded. Each study was screened independently, followed by final study selection after discussion with all authors. Primary meta-analysis used Cox proportional hazards regression with pseudo-individual-subject data reconstructed from published Kaplan-Meier curves (Guyot method) and a Tierney events + P value derivation for one study without Kaplan-Meier data. A sensitivity analysis pooled odds ratios (ORs) at the 6-month clinical response endpoint. Primary outcomes include improvement in MRONJ clinical staging. Secondary outcomes include time to improvement, adverse effects, radiographic evaluation, and presence of serum markers. After review of 162 studies, 5 (3.1%) studies were included in the systematic review with 3 (1.9%) studies included in the meta-analysis (n = 101 subjects). A three-study Cox hazard ratio (HR) meta-analysis yielded a pooled HR of 5.35 (95% CI, 3.14 to 9.13, P < .0001, I2 = 0%) favoring TPTD. Subgroup analyses by dosing regimen showed directionally consistent effects (daily pooled HR = 12.52; 95% CI, 5.75 to 27.23; weekly pooled HR = 8.09; 95% CI, 3.59 to 18.26; both I2 = 0%), and an OR-based sensitivity analysis at the 6-month binary healing endpoint was directionally concordant (pooled OR = 14.26; 95% CI, 2.83 to 71.77). Adjunctive TPTD shows improvement of MRONJ staging and time to healing compared to conventional treatments alone, but the magnitude of the impact remains unclear. Additional evidence, including studies evaluating dosing regimens and subject segmentation by MRONJ staging, is warranted.
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Drug Discovery Landscape
1 orphan drug designation for Osteonecrosis of the jaw.
1 orphan drug designation for Osteonecrosis of the jaw.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Recombinant human platelet derived growth factor BB | proteins | FDA | 2007-02-01 | — | Luitpold Pharmaceuticals, Inc. |
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