MRONJ Treatment Strategies: A Systematic Review and Two Case Reports
<p>Role of the bone remodeling unit (BMU) in bone remodeling process.</p> "> Figure 2
<p>Chemical formula of pyrophosphate to BPs.</p> "> Figure 3
<p>Chemical structure of BPs.</p> "> Figure 4
<p>Chemical structure of the molecule of zoledronic acid (zoledronate).</p> "> Figure 5
<p>Effect of DB and BP on bone resorption.</p> "> Figure 6
<p>Mechanism of action of BPs on the bone.</p> "> Figure 7
<p>Literature search Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.</p> "> Figure 8
<p>Initial lesion showed in OPT pointed by the circle.</p> "> Figure 9
<p>CBCT of the initial lesion pointed by the circle.</p> "> Figure 10
<p>(<b>A</b>) Surgical site after incision; (<b>B</b>) Delimitation with piezo surgery; (<b>C</b>) Bone plug removed with piezo surgery only.</p> "> Figure 11
<p>(<b>A</b>) PRF preparation; (<b>B</b>) PRF autologous membrane.</p> "> Figure 12
<p>(<b>A</b>) Surgical site after 7 days; (<b>B</b>) Complete healing after 14 days since surgery.</p> "> Figure 13
<p>OPT of initial lesion pointed by the circle.</p> "> Figure 14
<p>(<b>A</b>) Piezo surgery intervention with OT7 Mectron<sup>®</sup> tip; (<b>B</b>) Delimitation of necrotic area; (<b>C</b>) Removal of necrotic bone plug; (<b>D</b>) Rounding of lesion margins with PL3 Mectron<sup>®</sup> tip.</p> "> Figure 15
<p>(<b>A</b>) Control of surgical site after 7 days; (<b>B</b>) Control of surgical site after 14 days (fully healed).</p> ">
Abstract
:1. Introduction
1.1. Pathogenesis
- More rapid bone turnover than in the long bones;
- Terminal-type vascularization;
- Mucoperiosteal lining overlying the bone tissue is easily subject to trauma;
- Presence of microflora/biofilm in the oral cavity;
1.2. Most Associated Drugs with MRONJ
- Tyrosine kinase inhibitors (TKIs) such as sunitinib;
- Additional monoclonal antibodies, angiogenesis inhibitors, such as bevacizumab;
- Fusion proteins such as aflibercept;
- mTOR inhibitors such as everolimus;
- Radiopharmaceuticals such as radium-223;
- Estrogen inhibitors such as raloxifene;
- Immunomodulators (methotrexate and corticosteroids) [14].
1.3. Half-Life
1.4. Mechanism of Action
1.5. Risk Factors Associated with MRONJ
1.6. Local Causal Factors
1.7. Staging
- Stage 0—Clinical symptoms and nonspecific radiological signs without exposure of the bone;
- Stage I—Exposed bone <2 cm with or without pain;
- Stage II—Exposed bone between 2 and 4 cm with pain responsive to nonsteroidal anti-inflammatory drugs (NSAIDs);
- Stage III—Exposed bone >4 cm with pain not responsive to NSAIDs + complications (fistulae, maxillary sinus, or inferior alveolar nerve involvement) [21].
1.8. Actual Practice Guideline
2. Materials and Methods
2.1. Protocol
2.2. Data Sources and Search Strategy
2.3. Inclusion and Exclusion Criteria
2.4. Study Selection and Characteristics
3. Results
4. Discussion
4.1. Medical Treatment
4.1.1. Antiseptic Therapy
4.1.2. Antibiotic Therapy
4.1.3. Pain Relief Therapy
4.1.4. Teriparatide Therapy
4.1.5. Pre- and Postsurgery Pharmacological Protocols
4.2. Laser Therapy
4.3. Minimally Invasive Surgery: Debridement
4.4. Surgical Resection
4.5. Fluorescence-Guided Bone Surgery
4.6. Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), Concentrated Growth Factor (CGF), and Piezosurgery (PZ)
4.7. Vascular Endothelial Growth Factor (VEGF) and Hyaluronic Acid (HA)
4.8. Ozone Terapy
5. Case Reports
5.1. Case Report 1
5.2. Case Report 2
6. Limitations
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AAOMS | American Association of Oral and Maxillofacial Surgeons |
ARONJ | Antiresorptive agent-related osteonecrosis of the jaw |
ARAs | Antiresorptive agents |
APC | Autologous platelet concentrates |
BRONJ | Bisphosphonate-related osteonecrosis of the jaw |
BPs | Bisphosphonates |
BFF | Buccal fat flap |
CRP | C reactive protein |
CONJ | Chemo-osteonecrosis of the jaws |
CGF | Concentrated growth factor |
CT | Conservative treatment |
CTX | C-terminal telopeptide of type 1 collagen |
DB | Denosumab |
DRONJ | Denosumab-related osteonecrosis of the jaws |
FDG PET-CT | Fluorodeoxyglucose positron emission tomography with computed tomography |
HA | Hyaluronic acid |
HBO | Hyperbaric oxygen; IPR: inflammatory, proliferative, remodeling |
LLLT | Low level laser therapy |
MRONJ | Medication-related osteonecrosis of the jaws |
MMF | Mylohyoid muscle flap |
NBPs | Non-aminobisphosphonates |
NSAIDs | Nonsteroidal anti-inflammatory drugs |
N.R. | Not reported |
OHIP-G14 | Oral health impact factor-g14 |
ONJ | Osteonecrosis of the jaws |
OPG | Osteoprotegerin |
ORN | Osteoradionecrosis |
PR | Periosteal reaction |
PZ | Piezosurgery |
PRF | Platelet rich fibrin |
PRP | Platelet-rich plasma |
P | Prospective |
RCT | Randomized clinical trial |
RANK | Reactive activator of nuclear κb |
R | Retrospective |
ST | Surgical treatment |
TKIs | Tyrosine kinase inhibitors |
VAS | Visual analog scale |
VEGF | Vascular endothelial growth factor |
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Articles screening strategy | KEYWORDS: (denosumab OR bevacizumab OR adalimumab OR romosozumab) AND osteonecrosis AND (treatment OR therapy) AND jaw |
Boolean Indicators: (“A” AND “B”) | |
Timespan: from 8 January 2006 to 8 January 2023 | |
Electronic Database: PubMed, Cochrane, Scopus, Web of Science, and Embase |
Authors (Year) | Study Design | MRONJ-Stage (n. Patients) | N. Total Patients (n. Lesions) and Type of Primary Disease (n. Patients) | Average Age (Years) | Types of Antiresorptive Drugs (n. Patients) and Duration of Therapy (Months, Years) | Description of Treatment (n. Patients) | Follow-Up (Months) | Outcomes |
---|---|---|---|---|---|---|---|---|
Hayashida, S. (2017) [26] | R | I and II (356) III (71) | 427 Neoplasms (236) Osteoporosi (191) |
CT: 72.7 ± 10.7 ST: 73.2 ± 10.3 |
DB (107) BP (320) for 28.8 months | CT (236): antiseptic mouth rinse, systemic antimicrobial agent, or debridement. ST (191): conservative surgery, removal of only the necrotic bone; extensive surgery, removal of the necrotic and surrounding bone; marginal mandibulectomy or partial maxillectomy. | 15 months | Better outcome in low-dose antiresorptive agent and ST. Better outcome of extensive ST surgery vs. CT. According to multivariate analysis, 4 variables are significantly correlated with treatment outcome: high-dose administration of an antiresorptive agent, serum albumin level, discontinuing drug, and surgical treatment. |
Schiodt. et al. (2017) [27] | P | I (86) II (191) III (34) N.R. (9) | 327 Neoplasms (327) | 67 | DB (63) for 15.7 months DB + BP (69) for 40 months BP (196) for 26.2 months | ST (102, 31%): debridement, sequestromy, resection with or without jaw reconstruction, curettage, and teeth extraction. CT (300, 92%): antibiotics, oral rinses, analgesics, and antifungal/antimycotic. | 11 months | Patients exposed to both DB and BP did not present with higher proportions of stage III ONJ or severe symptoms. Rates of associated local oral risk factors (such as tooth extractions) were similar in patients with combined exposure to DB and BP vs. those exposed to single agent antiresorptive. Patients that discontinued antiresorptive treatment between baseline and 3 months had a higher percentage of stage III MRONJ |
Watanabe (2021) [28] | R | II (206) III (46) | 252 Neoplasms (133) Osteoporosis (119) | 71.2 ± 9.9 |
DB (46) for 81.7 months BP (206) for 18.3 months | 138 (54.8%) underwent surgery, and 143 (56.7%) received HBO therapy. | ≥3 months | In the univariable analysis, therapeutic effect of surgery in both stage II and III vs. therapeutic effect of HBO in stage II. In the multivariable analysis for stage II, stronger association with healing of extensive surgery vs. conservative surgery. ≥46 sessions of HBO therapy less associated with healing vs. non-HBO therapy. |
Favia (2016) [21] | R | I: 23 Ii: 187 III: 101 | 244 (322) Neoplasms (172) Osteoporotic (72) | N.R. | DB (13) DB + BP (3) BP (228) | ST based on the dimensional staging Stage I: surgical debridement; stage II: small open-access surgery with piezosurgery of bone margins; stage III: wide open-access surgery with extensive bone resection and piezosurgery of bone margins. | 16 months | Dmab-MRONJ is in stage II or III, requiring a more or less invasive surgical approach. Complete clinical and radiological healing in 86.9% of lesions, recurrence in 13.1% recurred (in patients who could not interrupt chemotherapy, steroids, and/or antiresorptive drugs). |
Kaibuchi (2021) [29] | R | I (26) II (76) III (27) | 129 Neoplasm (72) Osteoporosis (57) | 74.3 ±11.5 | DB (40) BP (89) | CT (71): mouth rinse (saline or povidone-iodine) and systemic antibiotics CT + ST (58): removal of sequestrum | 60 months | Cure rate higher in patients with osteoporosis vs. in those with cancer and in patients who had separation of sequestrum vs. in those who did not. |
Yoshida T. et al. (2021) [30] | R | I (13) II (91) III (19) | 123 osteoporotis: (123) | 75.1 ± 8.4 | DB (11) for 8.9 months BP (112) for 91.1 months | ST: 82 (66.7%) CT: 41 (33%) | >3 months | ARONJ is frequently located in the mandible (55.3%), and the most frequent initiating event is periodontitis (42.3%). The most common type of ARONJ is BRONJ (91.1%). Most patients continued the ARA therapy (80.5%). No significant difference in the healing rates between the continued group and discontinued group. |
Favia (2018) [31] | R | I (11 lesions) II (65 lesions) III (55 lesions) | 106 (131) Neoplasm (95) Osteporosis (36) |
ST: 70.2 CT: 71 | DB (20) DB + BP (7) BP (103) | ST (85 patients, 107 lesions): perioperative antibiotics, surgical removal of the necrotic bone, from simple surgical debridement for smaller MRONJ to extensive bone resection for larger lesions. CT (21 patients, 24 lesions): chlorhexidine, periodic dental checks, systemic antibiotic, monthly low-level laser therapy, and removal of bone sequestrum. | 12 months | Complete healing in all the surgically treated lesions showed, except for 13.5% of the lesions (from stage III to stage I). Stabilization without complete healing in all the lesions with conservative treatment |
Hadaya (2018) [32] | R | I (47) II (32) III (4) | 106 Neoplasm (89) Osteoporosis (34) | 71.7 | DB (17) BP (98) for 5.5, 3.7, and 4.8 years | Local wound care: mechanical vigorous debridement and cleaning of exposed bone, oral antibacterial solution (chlorhexidine), and antibiotics. | 24 months | Complete disease resolution in 71% of lesions, disease improvement in 22%. Association of wound care score with disease resolution and time to resolution. No effect on resolution of demographics, anatomic site, condition, and type and time of antiresorptive treatment. |
Wei et al. (2022) [33] | R | I (29) II and III (87) | 95 (122) Prostatic cancer (95) | 75.17 ± 8.49 | DB (42) DB + BP (17) BP (57) for 18 months | Stage I: conservative treatment with chlorhexidine mouth rinse. Stage II: chlorhexidine mouth rinse, Antibiotics, and/or analgesics. Stage III: superficial debridement, sequestrectomy, or bone resection. | 12 months | Cumulative response rate of patients treated with DB is 70.5%. DB, pretreatment level of CTX > 150 pg/mL, and anemia are independent prognostic factors of MRONJ in a multivariate analysis. |
Osaka (2021) [34] | R | I (15) II (51) III (22) | 88 Neoplasms (15) Osteoporosis (73) | 80.5 ± 6.7 | DB: 28 BP: 60 (for 49.1± 33.4) | CT: antimicrobial mouthwash, systemic antimicrobials, or debridement of bony sequestra. ST: Conservative surgery: removal of necrotic bone area. Extensive surgery: removal of the necrotic and surrounding bone, marginal mandibulectomy, or partial maxillectomy. | 23 months | According to univariate analysis, 3 variables significantly correlated with prognoses: sex, dosage, and the treatment method. According to multivariate analysis, 2 variables significantly correlated with the prognosis: high-dose administration of an antiresorptive agent. |
Ristow (2018) [35] | R | I (31) II (26) III (11) | 87 (104) Neoplasms (79) Osteoporosis (8) | 66.25± 9.58 | DB (33) DB + BP (12) BP (42) for 50.37 ± 32.55 months | Mylohyoideus muscle flap (MMF) for the lower jaw: 57 patients Pedicled buccal fat flap (BFF) for the upper jaw; 30 patients | 8 months | Mucosal integrity in 88.0% (44/50) of patients in the MMF group and 93.1% (27/29) of patients in the BFF group. No serious side effects were reported. Better outcome of stage I and II vs. stage III. |
Coropciuc (2017) [36] | R | I (57) II (47) III (5) | 79 (109) Neoplasms (79) | 70 | DB (43) BP (36) | ST: minimally invasive approaches (sequestrectomy, debridement of soft tissue, and application of leucocyte and PRF) CT: oral rinses and antibiotics | ≤24 months | Complete healing and resolution of disease in 38/57 stage I lesions, 30/47 stage II lesions, and 3/5 stage III lesions. Improvement of symptoms in 16/47 stage II lesions and 2/5 stage III lesions. Fifteen of the stage I lesions and one of the stage II lesions failed to respond. |
El-Rabbany (2019) [37] | R | I (15) II (46) III (17) | 78 Neoplasms (12) ( Osteoporosi (66) | 77.2 | DB (17) for 5 years BP (61) for 5 years | ST (56): debridement, curettage, sequestrectomy, cauterization, and resection. CT (22): local and/or systemic antimicrobial therapy, hyperbaric oxygen therapy, pentoxifylline, and teriparatide. | ST: 15.5 months CT: 11 months | Disease resolution in 39 ST patients (70%) vs. 8 CT patients (36%). ST was associated with disease resolution vs. CT alone, after adjustment for age, duration of antiresorptive or antiangiogenic therapy, whether the antiresorptive or antiangiogenic agents were used for oncologic purposes, and the stage of MRONJ at initial presentation. |
Sánchez-Gallego Albertos (2021) [38] | R | II (4) II (52) III (14) | 70 Neoplasms (36) Osteoporosis (34) | 50–70 | DB (10) BP (60) for 6–12 months | Surgical treatment: resection of necrotic bone, sequestrae and refreshing bone margins with a drill, extraction of the teeth if they were near the necrotic bone, and PRP placement. | 2–52 months | More recurrence (18.6%) in breast cancer patients, smokers, and patients that had been administered zoledronic acid. Smoke is the only independent risk factor. |
Akashi (2018) [39] | R | I (17) II (28) III (15) | 61 MRONJ Neoplasms (28) Osteporosis (33) 27 ORN |
74 MRONJ 68 ORN |
DB (10) DB + BP (10) BP (41) | CT (14) Minimal debridement (1) ST (1): resection with or without reconstruction. | N.R. | In MRONJ group: higher median age, higher nr. of females, use of steroids, history of pain, periosteal reaction, and tooth extraction. Minimal debridement was significantly performed in the MBROJ group. Surgical resection was performed in the ORN group. |
Hallmer F. et al. (2018) [40] | P | I (10) II (36) III (9) | 55 (55) Neoplasms (24) Osteoporosis (31) | 63.6 (M)- 73.1 (F) | DB (12) DB + BP (11) BP (32) | ST was sequestrectomy in patients without progressive bone disease or block resection patients with progressive bone disease with ongoing bone destruction. | 15.8 months | Prevalence of MRONJ is 3.64% in those on high-dose DB. Periodontal disease preceded development of MRONJ in 41 patients. Remission or healing in 80% of patients treated with sequestrectomy and in 92.5% of patients treated with block resection. |
Ristow O et al. (2021) [41] | R | I: 86 | 55 (86) Neoplasm (46) Osteoporosis (9) |
68.2 ± 8.5 (F) 72.5 ± 10.4 (M) | BP (24) DB (25) DV + BP (5) for 49.3 ± 41.5 months | Surgical treatment: VELscope system Vx. Bone resection performed until the bright fluorescence of healthy bone was observed. Visible bone group (46 lesions): bone visibly exposed to the oral cavity. Probable bone group (40 lesions): could be probed to bone through the sinus tract. | ≤8 week | Intraoperatively, the necrotic lesions were significantly larger vs. preoperative mucosal lesions in both groups. There is a significant but very weak relationship between the extent of the mucosal lesions and the necrotic bone area. |
Otto Sven (2016) [42] | P | I (4) II (42) III (8) | 54 Oncologic (45) Osteoporotic (9) | 71.4 ± 9.2 | DB (3) DB + BP (47) BP (4) for 46.3 months | Fluorescence-guided surgery: complete removal of necrotic bone, monitored using the visually enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. | 12.9 months | Intact mucosa in absence of exposed bone, pain, or signs of infection in 47/54 patients (87%) and in 56/65 lesions (86.2%) after first surgery. In 4 patients with 6 lesions, a second fluorescence-guided surgery was necessary. In total, 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. |
Kojima Y. (2022) [43] | R | I (9) II (30) III (14) | 53 Neoplasms (33) Osteoporosis (22) | 74.9 ± 11.9 | DB (16) DB + BP (5) BP (32) for 47.0 ± 33.9 months | CT: oral hygiene guidance, antibacterial mouthwash, local lavage, administration of oral antibiotics, removal of mobile segments of bony sequestrum, and extraction of symptomatic teeth. | 729 ± 494 days | Clinical symptoms of 15 (28.3%) disappeared or improved while worsening was observed in 6 (11.3%). Enlargement of the osteolytic lesion occurred in 17 (32.1%) patients. CT is successful in 12 (22.6%) patients and unsuccessful in 41 patients (77.4%). Patients with stage III MRONJ have worse outcomes. The MRONJ stage and primary disease are not associated with the enlargement of osteolysis on the radiological images. A periosteal reaction on radiological examination is correlated with poor comprehensive treatment outcomes. |
Eguchi (2017) [44] | R | II (52) | 52 Neoplasm (35) Osteoporosis (17) | CT: 74.8 ± 10.3 ST: 72.3 ± 11.3 | DB +/− BP (38) BP (14) | CT (24): debridement, systemic antibiotics, analgesics, and incisional drainages. ST (28): necrotic bone resection. | 6 months | CT: success in 8/24 pts (33.3%) ST: success in 25/28 pts (89.3%) |
Blatt (2022) [45] | P | I (41) II (10) III (1) | 52 Neoplasm (52) | 71.5 ± 8.6 | N.R. | Arm A: resection of necrotic bone and fistulas; sufficient, vascularized, and mechanically stable wound coverage. Arm B: surgical treatment + PRF membrane on the decorticated bone before covering. | 6 weeks | Dehiscence and mucosal integrity after surgery in 16 cases (30.76%). No significant differences in VAS score, PWAT score, and IPR wound healing score. |
Ahrenbog (2020) [46] | P | III | 44 Neoplasms (37) Osteporosis (7) | 68.1 | DB (4) DB + BP (8) BP (32) for 56.4 months | ST: removal of the resected bone, sharp bone edges, and the surface were smoothed till visible bleeding was reached. Afterward, wound closure was performed by using different techniques (mylohyoid muscle flap and buccal fat flap). | 13.2 months | Relapses in 12 cases and mucosal integrity in 38. Cases treated with the muscle or fat flap showed better results regarding the recurrence rate and soft tissue healing. Pain level was reduced significantly. Partial hypoesthesia of the lip arose in 18 cases. |
Mamilos (2021) [47] | P | III (44) | 44 Neoplasm (22) Osteoporosis (22) | 68.1 | DB (4) DB + BP (8) BP (32) | ST: necrotic bone area resection or continuity resection of the mandibular. Analysis of CRP and leukocytes at baseline. | 13.2 months | The stage of chronic inflammation is correlated with the amount of vital bone and the success of surgery. If acute inflammation is dominant, chronic inflammation areas are found less, while necrotic areas are observed more. The risk of relapses, wound healing disorders, and the level of CRP are elevated if acute inflammation is severe or moderate. |
Moll (2021) [48] | P | III (43) | 43 Neoplasm (36) Osteoporosis (7) | 68 | DB (13) DB + BP (9) BP (39) for ≥63/<63 months | Surgical treatment: necrotic bone area resection, perioperative, and antimicrobial mouth rinse with chlorhexidine. | 21.86 weeks | Significant improvement of EORTC QoL-H&N35 and the Oral Health Impact Factor-G14 (OHIP-G14) questionnaire |
Soutome (2020) [49] | R | II (18) III (20) | 38 Neoplasms (17) Osteoporosis (21) | 74.3 |
DB (14) BP (24) for 4 years | 38 MRONJ patients with PR Type 1: new bone is formed parallel to the mandible, and no gap was evident between the mandible and new bone; type 2: new bone is formed parallel to the mandible, and a gap was evident between them; type 3: an irregular shape. Segmental mandibulectomy (9) Marginal mandibulectomy (29) | ≥3 months | Inflammatory tissue in the area visualized as a gap on CT at histological examinations. Presence of bacteria in the type 2 or type 3 PR at bacteriological examination. Complete cure in 21 of 38 (55.3%) patients, lower than the cure rate of 73.4% in 143 patients without PR. Cure rate lower in cases with type 3 PR or with persistent osteolysis. |
Fleisher (2016) [50] | R | II (31) III (3) | 31 (33) Neoplasms (31) | 64 |
DB (10) DB + BP (3) BP (18) for 47 months | ST: marginal resection with a saw or bur and osteotome to resect sequestra, necrotic bone, reactive bone, and clinically uninvolved bone that was identified by FDG uptake. Low-risk group (type A): 22 patients with activity limited to the alveolus, torus, and/or basal bone superior to the mandibular canal. High-risk group (type B): 11 patients with type A FDG activity with extension inferior to the mandibular canal. | 6.6 months | Treatment of type A MRONJ lesions was more successful than treatment of type B MRONJ lesions. 7 of the type B failures were successfully retreated by segmental resection and reconstruction. |
Klingelhöffer et al. (2016) [51] | P | I (34) II (36) III (6) | 29 Neoplasms (33) Osteoporosis (4) Rheumatoid arthritis (3) | 70.9 | 20/20 | Preoperatory antibiotics and ST | 55 weeks | Long-term maintenance of the mucosal closure in 27.6% of patients. Stage II patients decreased to stage I in 81% after surgery, and stage III patients improved in 83% of cases. Stage I patients profited only in 38% by surgical intervention. MRONJ recurrence after surgery is associated with extended preoperative MRONJ duration. MRONJ of the upper jaw seems prognostically more favorable. |
Hauer (2020) [52] | R | I (3) II (24) III (5) | 26 Osteoporosis (26) | 73.4 | DB (8) DB + BP (4) BP (16) for 73.1 months | ST: radical removal of necrotic bone was performed by resection with the borders in nonvital bone, followed by removal of residual osteonecrosis by rotary burr into the viable bleeding bone margins and under VELscope control. In lesions with sequestration, the sequestrectomy is performed, and the remaining necrotic bone is then radically removed by rotary burr. | 20.5 months | Complete healing was observed in all patients, in 9% of cases by secondary intention, in the mean period of 6 weeks. |
Hoefert et al. (2017) [53] | R | I (1) II (10) III (6) | 17 Neoplasms (16) Osteoporosi (1) | 68.5 ± 12.0 | DB 120 mg (17) DB 60 mg (2) for 19.7 ± 10.5 months | Major ST (5): sequestrectomy, bone smoothing, tension-free tissue coverage, and drainage. Minor ST (1): palatal sequestrectomy and soft tissue closure. CT: (10): surface debridement, local rinses, and intermittent antibiotics. | 348 ± 329 days | Pain at the first visit in 47% of patients, of which 24% had pressure-like pain. The majority of MRONJ are at sites of dental prostheses-induced pressure sores (41%) or dental extractions (35%). Complete healing is significant in patients treated with major ST (80%) vs. CT (20%). DB is discontinued in 60% of nonoperative patients and major ST patients with no effect on healing. Histologic findings exhibit fewer osteocyte lacunae, and micro-CT reveals trabecular thickening. |
Pichardo (2016) [54] | R | II (2) III (9) | 11 Neoplasms (7) OsteoporosiS (4) | 72.6 |
DB: 6 DB + BP: 5 For 17 months | ST: debridement with cauterization of the bone + antimicrobial treatment. | 16.4 | Healing in 9 patients |
Beaudouin (2021) [55] | R | I (6) | 6 Neoplasm (6) | 66.5 | DB (6) | Surgical treatment: necrotic bone area reSection 5–9 months after Dmab withdrawal. Conservative treatment: oral hygiene, antibacterial mouthwashes, systemic antibiotic therapy, and not wearing overlying dentures. | 23.5 months | Dmab was stopped in MRONJ patients, with favorable outcomes for 3 cases and stabilization in 4 cases. |
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Inchingolo, A.M.; Malcangi, G.; Ferrara, I.; Patano, A.; Viapiano, F.; Netti, A.; Azzollini, D.; Ciocia, A.M.; de Ruvo, E.; Campanelli, M.; et al. MRONJ Treatment Strategies: A Systematic Review and Two Case Reports. Appl. Sci. 2023, 13, 4370. https://doi.org/10.3390/app13074370
Inchingolo AM, Malcangi G, Ferrara I, Patano A, Viapiano F, Netti A, Azzollini D, Ciocia AM, de Ruvo E, Campanelli M, et al. MRONJ Treatment Strategies: A Systematic Review and Two Case Reports. Applied Sciences. 2023; 13(7):4370. https://doi.org/10.3390/app13074370
Chicago/Turabian StyleInchingolo, Angelo Michele, Giuseppina Malcangi, Irene Ferrara, Assunta Patano, Fabio Viapiano, Anna Netti, Daniela Azzollini, Anna Maria Ciocia, Elisabetta de Ruvo, Merigrazia Campanelli, and et al. 2023. "MRONJ Treatment Strategies: A Systematic Review and Two Case Reports" Applied Sciences 13, no. 7: 4370. https://doi.org/10.3390/app13074370