Next Article in Journal
Hidden Asymmetries: Leg Length Discrepancy and Breast Asymmetry in Adolescent Scoliosis and Postural Disorders—A Cross-Sectional Study
Previous Article in Journal
Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Clinical Effectiveness of Surgical Marginal Resection with Piezoelectric Device on Bisphosphonate-Related Osteonecrosis of the Jaws: A Retrospective Study

Department of Neurosciences, Section of Clinical Dentistry, University of Padova, 35121 Padova, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(11), 3792; https://doi.org/10.3390/jcm14113792
Submission received: 7 May 2025 / Revised: 22 May 2025 / Accepted: 27 May 2025 / Published: 28 May 2025
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

Abstract

:
Background: In 2020, the definition of Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) was revised. The current definition is Medication-Related Osteonecrosis of the Jaws (MRONJ), to underline the fact that not only bisphosphonates are implicated in the onset of the disease. This study aims to investigate the efficacy of marginal resection using a piezoelectric device in patients with BRONJ. Methods: A retrospective study was conducted on subjects treated at the Dental Clinic University Hospital of Padua (Italy) from January 2017 to April 2024. Only patients diagnosed with BRONJ stages 1 and 2, who underwent marginal resection of the maxillae using a piezoelectric instrument were included. Patients who had received radiotherapy to the head and neck region, those with MRONJ, and those with primary tumors of the maxillary bones were excluded. Marginal resection was considered an effective treatment when complete epithelialization of the surgical site was achieved, with no signs or symptoms of disease, and the condition remained stable one-year post-operation. Results: In total, 21 patients (17 females and 4 males) were selected. A single resection was performed for each patient, resulting in a total of 21 surgeries: 14 in the mandible and 7 in the maxilla. At one-year post-surgery, 20 patients showed no signs or symptoms of the disease. One patient experienced two recurrences, both of which were subsequently treated. Conclusions: marginal resection using a piezoelectric device is an effective procedure for the treatment of BRONJ, although it remains a relatively invasive and destructive therapeutic approach.

1. Introduction

In 2020, the definition of Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) was revised and redefined as an adverse drug-related reaction, characterized by the progressive destruction and necrosis of the mandibular and/or maxillary bone in individuals exposed for more than 8 weeks to antiresorptive drugs treatment, for which an increased risk of disease has been established, in the absence of prior head and neck radiotherapy [1,2]. The current definition of osteonecrosis is Medication-Related Osteonecrosis of the Jaws (MRONJ), to underline the fact that other drugs, not only bisphosphonates, are implicated in the onset of the disease [3,4]. Along with this new definition, the terms “major” and “minor” diagnostic criteria for BRONJ diagnosis have been eliminated [5]. The Italian Society of Oral Pathology and Medicine and the Italian Society of Maxillofacial Surgery (SIPMO-SICMF) have provided a list of clinical and radiographic signs and symptoms for the presentation of MRONJ, without distinguishing between major and minor criteria [6,7]. There have also been changes in the recommended treatments: the surgical approach, previously reserved for advanced stages of the disease, is now indicated and extended to less severe stages of MRONJ [8,9].
The pathophysiology of MRONJ is complex and multifactorial, involving suppression of bone turnover, infection, inflammation, and angiogenesis inhibition [10,11]. Recent studies have also highlighted the role of genetic factors in MRONJ susceptibility [12,13]. The incidence of MRONJ varies depending on the type and duration of antiresorptive therapy, with higher rates observed in cancer patients receiving high-dose intravenous bisphosphonates or denosumab [14,15].
Prevention strategies for MRONJ have been extensively studied and include dental screening before initiating antiresorptive therapy, maintaining good oral hygiene, and avoiding invasive dental procedures when possible [16,17]. When dental interventions are necessary, antibiotic prophylaxis and minimally invasive techniques are recommended [18].
In this new context, the surgical marginal resection intervention performed using piezoelectric instruments in MRONJ patients is introduced as a promising treatment option [19,20]. Piezoelectric surgery offers several advantages over traditional rotary instruments, including selective cutting of mineralized tissues, improved visibility, and reduced risk of soft tissue damage [21].

Piezoelectric Devices in Medical–Dental Applications

Modern piezoelectric devices, widely used in the medical and dental fields, rely on the piezoelectric effect, discovered in 1880 by Pierre and Jacques Curie [22]. The inverse piezoelectric effect, discovered later by Gabriel Lippmann, also found applications in biomedical fields in the 2000s [23]. The piezoelectric effect occurs when mechanical deformation generates an electric charge in certain materials, while the inverse effect involves applying an electric field to cause mechanical deformation [24].
These devices use materials, typically crystalline ceramics, that deform when exposed to an electric current, generating vibration. This vibration is transferred to a working insert in devices that operate at frequencies between 24 and 40 KHz, commonly referred to as ultrasonic devices [25,26,27].
Ultrasonic piezoelectric devices are preferred in dental surgery due to their ability to precisely cut hard tissues, reducing the risk of damage to sensitive structures such as the inferior alveolar nerve or soft tissues like the gingiva and maxillary sinus membrane [28,29]. They can be used for procedures such as osteotomy, access to bone lesions, or foreign body removal [30,31,32]. The precision of these devices helps minimize damage, promotes faster bone healing, and results in less postoperative pain compared to traditional rotary tools [33,34]. It can be used in several clinical situations, such as the accidental displacement of foreign bodies into the maxillary sinus, to gain access to teeth or alveolar bone lesions, and to perform osteotomy in maxilla and mandible, such as in cases of bone lid surgery in posterior mandible [35,36].
Piezoelectric surgery also benefits from cavitation effects—when the vibrating insert interacts with irrigation solution, it forms micro-bubbles that help reduce bleeding and improve visibility during surgery [37]. These bubbles also have bactericidal properties and aid in cleaning bone debris [38]. Overall, piezoelectric devices are considered atraumatic, minimally invasive, and effective in enhancing surgical outcomes [39,40,41].
This paper aims to evaluate the effectiveness of marginal surgical resection with piezoelectric devices, as part of minimally invasive ultrasonic surgery, in the treatment of BRONJ. Specifically, the surgical procedure will be assessed in terms of healing and recurrence, in line with the prognostic indices present in the clinical-therapeutic recommendations of the SIPMO-SICMF [42].

2. Materials and Methods

This retrospective study reviewed medical records and histological examinations of 274 potentially eligible patients treated at the Dental Clinic of Padova from January 2017 to April 2024. This study focused on a series of BRONJ cases that were unresponsive to medical therapy and underwent marginal surgical resection using piezoelectric devices.

2.1. Inclusion and Exclusion Criteria

Table 1 summarizes inclusion and exclusion criteria.
For each patient, the following data were collected: gender, age, smoking status, comorbidities, BRONJ triggers, osteonecrosis resection site, bisphosphonate treatment indication, bisphosphonate type, and the presence of actinomyces in histological examinations.
In this study, we used the SIPMO-SICMF staging, which differs in some details from the AAOMS staging system [43]. The corresponding stages are presented in Table 2 and Table 3. Presurgical (T0) clinical-radiographic signs and symptoms of BRONJ were recorded, as shown in Figure 1. From the orthopantomography (OPG), computed tomography (CT), or cone beam computed tomography (CBCT), the dimensions in millimeters of the lesion to be excised were predefined.
The surgical procedures were performed in a sterile environment, under conscious sedation, and by the same lead surgeon. After local anesthesia (Articaine Hydrochloride and Bupivacaine Hydrochloride), a mucoperiosteal flap was raised to expose the necrotic tissue. The osteotomy lines were made using a piezoelectric device and occasionally completed with a manual chisel. Finally, the tissue was excised. Intra-operatively, the surgical margins were adjusted, if necessary, based on the consistency, color, and bleeding of the bone tissue. The closure was achieved by first intention using resorbable sutures. Histological examination was requested for all cases.
All surgical procedures are presented in Figure 2.
Specifically, the marginal bone resection was performed using a piezoelectric device (PIEZOSURGERY® touch, Mectron, Carasco, Genoa, Italy) set to bone mode with a high-frequency vibration of up to 36 kHz. The ultrasonic vibration tips required for the procedures were OT7, OT8L, OT8R, and OT12 for osteotomies, and OP1 for osteoplasty.
As shown in Figure 3, in the post-operative period, the clinical signs and symptoms of BRONJ were reassessed, while radiographic evaluation was performed only at T2 and T3 to minimize the patient’s exposure to X-rays. For 9 days (3 days before and 6 days after the procedure), dual antibiotic therapy was prescribed: Amoxicillin and Clavulanic Acid (3 g/day) and Metronidazole (750 mg/day). In the post-operative phase, analgesic therapy (Paracetamol 3 g/day and Ibuprofen 1800 mg/day) and antiseptic therapy (0.2% chlorhexidine spray) were recommended to reduce pain and the microbial load in the oral cavity.

2.2. Success Criteria

The surgical marginal resection with a piezoelectric device was considered effective upon achieving the following criteria 1 year after surgery: absence of exposed bone in the oral cavity, complete epithelialization of the surgical site, and no clinical or radiographic signs or symptoms of BRONJ.
This study was conducted in accordance with the ethical principles outlined in the Helsinki Declaration and adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies [44,45]. The project was registered with the local ethics committee. Informed consent was obtained from all patients.

2.3. Statistical Analysis

A descriptive statistical analysis was performed on the data. Qualitative variables were presented as absolute frequencies and percentages, while quantitative variables were analyzed using the mean index. The data were analyzed and recorded using Excel 18.0-2021.

3. Results

Characteristics of all clinical cases are presented in Table 4 and Table 5 and summarize preoperative clinical and radiographic signs and symptoms, based on SIPMO-SICMF staging criteria.
A total of 21 patients were selected: 17 women (80.95%) and 4 men (19.05%). The average age was 74.38 years (range 63–86). In total, 9 patients (42.86%) were diagnosed with BRONJ stage 1, and 12 patients (57.14%) with BRONJ stage 2, based on the preoperative clinical and radiographic signs and symptoms and the SIPMO-SICMF staging criteria. Each stage was divided into asymptomatic (a) and symptomatic (b) cases. Regarding intra-oral triggers for osteonecrosis, the cause was not identified for 5 patients (23.81%). Overall, 7 patients (33.32%) were treated with bisphosphonates for osteometabolic reasons, mainly osteoporosis, and 14 patients (66.67%) for oncological reasons: 11 patients (52.38%) had bone metastases and 3 patients (14.29%) had Multiple Myeloma. Zoledronic acid (ZOL) had been prescribed for 15 patients (71.43%), Alendronate (ALE) for 4 patients (19.05%), and Ibandronate (IBA) for 2 patients (9.52%).
The most common comorbidities were hypertension, presented in 12 patients (57.14%), familial hypercholesterolemia presented in 5 patients (23.81%), and type II diabetes mellitus presented in 3 patients (14.29%). Other conditions, such as chronic kidney failure, were observed in less than 10% of the cases. In total, 10 patients (47.62%) were smokers.
Each patient underwent a single marginal resection, with a total of 21 surgeries performed: 14 resections (66.67%) were carried out on the mandible, and 7 resections (33.33%) on the maxilla. The operating time was found to be on average 48.81 min (with a standard deviation of 8.98 min). Values are listed in Table 6. All patients received histological confirmation of BRONJ, and in 9 samples (42.86%), actinomyces were found.
Table 7 presents clinical cases and corresponding clinical-radiographic signs and symptoms of BRONJ observed after piezoelectric marginal resection at follow-up (T1-T2-T3).
At the first follow-up (T1), 5 patients (23.81%) showed incomplete epithelialization of the surgical site, and other symptoms (trismus, lip dysesthesia) were present, although with reduced severity compared to the preoperative state. At 6 months post-resection (T2), in 1 patient (4.76%) (N°1), clinical and radiographic signs such as incomplete epithelialization, dysesthesia, and thickening of the trabecular bone were noted. At T3, the last follow-up, the same patient (N°1) showed worsening of the clinical picture with exposed bone in the oral cavity, lip dysesthesia, pain, and focal osteosclerosis. Pain was measured using the Visual Analogue Scale (VAS) and recorded a score of 4. This patient underwent two additional marginal resections using the piezoelectric device. For the following 3 years after the last resection, the patient was followed up biannually, with no further clinical or radiographic signs of BRONJ being observed.

4. Discussion

In this case series, the most frequent site of osteonecrosis was the mandible (66.67%). This result aligns with the literature, where the mandible is reported to be more commonly affected by BRONJ compared to the maxilla. In one study, the mandible was affected in 70% of cases, and in another study, in 60% [46,47]. The most widely accepted hypothesis is that the mandible is more susceptible to osteonecrosis due to its terminal vascularization [48]. The average age of patients at the time of surgery was 74.38 years (range 63–86), indicating that BRONJ tends to manifest in the 60–80 age group. This finding is consistent with numerous other studies, where the mean age ranges from 60 to 77 years [49,50,51]. One systematic review reports a mean age of 66.5 ± 4.7 years [52]. While the majority of patients fall within this age range, the onset of the primary condition and the initiation of bisphosphonate therapy may play a role in the age of BRONJ manifestation, as some studies report a mean age of 55.4 years [53].
Women represent most patients (80.95%), which is consistent with the higher incidence of BRONJ in women. Some studies suggest a gender ratio of approximately 3:1. This could be attributed to women’s longer life expectancy, the rising incidence of breast cancer, and the menopausal condition, which leads to a decrease in estrogen levels and consequently reduced bone mass. Regarding the primary condition for which bisphosphonates were prescribed, it can be said, in agreement with the international literature, that oncological patients develop BRONJ more frequently than osteometabolic patients [54]. The different potency of the drug, the route of administration, and the duration of bisphosphonate therapy all affect the outcomes. The role of periodontal disease as a risk factor for BRONJ, and more generally for inflammatory and infectious conditions in the oral cavity, has been extensively discussed [55]. Inflammation may induce bone necrosis both through the release of chemical mediators and via indirect action through edema, leading to reduced blood supply to the bone and subsequent necrosis [56].
Extraction surgery and implant therapy can connect the bone with the oral flora and induce trauma in tissues with altered metabolism and healing [57,58,59,60]. Poorly adjusted prosthetics also pose a local risk factor, as ill-fitting prostheses can exert excessive pressure, leading to thinning of soft tissues, ulceration, and bone exposure [61,62]. For 5 patients in this study (23.81%), no identifiable trigger for BRONJ was found. These cases may be due to anatomical predispositions or what is known as “spontaneous” drug-related ONJ, which may be associated with the patient’s pharmacogenetics, though there is insufficient evidence on this [63,64].
It is well-established that smoking causes vasoconstriction of blood vessels, leading to reduced blood flow to the bone and necrosis [65]. It also impairs wound healing, delaying the entire process [66]. In this study and in a similar paper, however, smoking did not seem to influence the surgical outcome, which might be due to patients either abstaining from smoking or reducing their daily cigarette consumption during the postoperative period [67].
In addition to the primary condition, comorbidities were observed, including hypertension, diabetes, and chronic kidney failure. The latter is considered a systemic risk factor for BRONJ, as excessive calcium excretion and inadequate renal reabsorption can disrupt calcium metabolism, also affecting the maxillary bones. Regarding hypertension, some studies have identified a correlation between high blood pressure and increased BRONJ risk, though the exact causal relationship remains unclear [68]. For diabetes, the literature does not yet provide a clear pathophysiological mechanism linking it to BRONJ onset. However, some studies suggest that microvascular damage caused by diabetes may also impact the bone tissue [69,70].
The histological confirmation of BRONJ was obtained for all cases, and the presence of actinomycetes was detected in the biopsy sample of 9 patients (42.86%), indicating superinfection of the necrotic bone.
The bacteria found in BRONJ are typically present in the oral cavity or are found in odontogenic and periodontal diseases. The most frequent pathogen in cases of bisphosphonate-induced osteonecrosis is, therefore, the actinomycete [71,72,73].
Piezoelectric instruments operate through the mechanical deformation of internal crystalline ceramics induced by an electric current. This deformation generates vibrations in the ultrasonic range, typically between 24 and 40 kHz, which are transmitted to the active tip of the ultrasonic insert.
The application of ultrasonic inserts in surgical procedures offers enhanced selectivity in cutting mineralized tissues, thus improving the preservation of surrounding soft tissues, particularly critical anatomical structures such as nerves and vessels. As noted by Bennardo et al. [74], the main limitation of piezoelectric instruments is the increased operative time compared to conventional osteotomies performed with rotary burs. However, the superior cutting selectivity enables cleaner and more precise osteotomies, as confirmed by Blaskovic et al. [75].
The literature presents conflicting evidence regarding the impact of piezoelectric devices on intraoperative bleeding. The cavitation effect generated by ultrasonic vibrations has been suggested to reduce bleeding and improve the surgical field’s visibility, as reported by Schlee et al. [37]. In contrast, a pilot study by Bennardo et al. found no statistically significant difference in bleeding compared to conventional osteotomy techniques [74]. Similarly, Walia et al. reported comparable levels of intraoperative bleeding during third molar extractions performed with piezoelectric and traditional methods [76].
Blaskovic et al. investigated bone healing in rats following osteotomies performed using three different methods: rotary bur, piezosurgery, and erbium laser. The study demonstrated that initial bone formation in defects prepared by piezosurgery was the most rapid, suggesting a potential advantage in postoperative bone regeneration [75].
Furthermore, Rocco et al. found that piezoelectric osteotomy was associated with significantly reduced postoperative pain and edema compared to traditional bur techniques [77]. The incidence of nerve injury was also lower in the piezoelectric group. Despite the greater safety profile concerning neural structures, the technique requires cautious application, particularly in anatomically complex regions [78].
Regarding the treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ), current evidence suggests that surgical intervention is more appropriate than medical therapy in patients with advanced stages of the disease. Conversely, conservative management appears to produce favorable outcomes in asymptomatic patients with early stage MRONJ, as highlighted by Saluki et al. [79]. A conservative surgical approach, when combined with various adjuvant non-invasive therapies, such as ozone therapy, low-level laser therapy (LLLT), or the use of autologous blood-derived products combined with Nd:YAG laser, has demonstrated partial or complete healing across all disease stages, indicating its potential as a viable therapeutic option for MRONJ [80,81].
At T0, the clinical and radiographic manifestation of BRONJ in the selected cases aligns with what is reported in the literature: in no cases were symptoms and/or signs found that differed from those already known. Pain, a frequent and debilitating component in BRONJ patients, was reported by approximately one-third of the patients (28.57%) [82]. The results indicate that, one year after surgery (T3), 95.24% of the treated cases meet the success criteria established by this study to evaluate the effectiveness of piezoelectric marginal resection in BRONJ patients: 20 patients, in fact, showed complete epithelialization of the surgical site and absence of clinical and radiographic signs and symptoms of the disease.
However, to date, no comparative studies are available assessing the efficacy of resective osteotomy performed using traditional techniques versus piezosurgery. Nonetheless, similar case series show results comparable to those of this research. In these two studies, a total of 29 piezoelectric marginal resections were performed in BRONJ patients, both oncological and osteometabolic. These studies suggest that ultrasonic resection provides positive clinical outcomes in the treatment of bisphosphonate-induced osteonecrosis of the jaws [83,84]. Another case series monitored 6 BRONJ patients who underwent a single piezoelectric marginal resection for a period of 60 months, without observing signs or symptoms of the disease in the long term: 5 years after ultrasound surgery, no recurrences were reported [85].
At T3, only one patient (4.76%) presented, in addition to the persistence of the symptoms and signs recorded at T2, a worsening of the clinical condition. This clinical case was successfully re-treated with two additional piezoelectric marginal resections, and 4 years after the last surgery, no further signs or symptoms of BRONJ were observed.
The evaluation of postoperative bleeding is absolutely complex as closed drains are not positioned or positionable which allow the bleeding to be quantified in terms of cubic centimeters. However, evaluation of any post-operative bleeding, following the classification most commonly used in the literature, i.e., absence of bleeding, moderate bleeding, profuse bleeding that required something more than local haemostatic measures such as re-intervention, transfusion, or endotracheal intubation, was evaluated. None of these patients experienced post operative bleeding, according to the classification report before [86,87,88].
While this paper analyzes and describes an effective resective technique, the most effective approach to ONJ remains preventive [89]. Furthermore, other surgical approaches besides bone resection by piezosurgery can be taken into consideration, as also reported by Grzegorz Dawiec et al. [90].
The strength of this paper is to purpose a safe technique to perform surgical treatment of this pathology.
A limitation, the weakness of the research is represented by the sample size, which can be considered adequate in relation to study design but relatively small compared to larger cohorts of subjects. There are also limitations related to the evaluation of the study variables and the retrospective data collection. It would be useful to perform a case control study with, for example, other surgical techniques. In this sample, surgery was performed in mild sedation and local anesthesia [91]. This case series was conducted in a single hospital facility, and the patients were selected only from those managed by a single medical team. Another limitation is the relatively short 12-month post-operative follow-up period.
The future direction is to expand the case study and record the data in a prospective study. In the future, topical healing promoters could also be used [92].

5. Conclusions

This study demonstrates that piezoelectric marginal resection is effective in the treatment of BRONJ, although it remains an invasive procedure. Further studies are needed to include larger cohorts of patients. Additionally, there is hope for the future development of more efficient piezoelectric devices in order to establish this type of surgery as the “Gold Standard” for drug-related osteonecrosis.

Author Contributions

Conceptualization, C.B. and M.B.; methodology, C.B.; validation, C.B. and C.M.; formal analysis, M.L.T.; investigation, C.M.; resources, M.L.T.; data curation, C.M.; writing—original draft preparation, M.L.T.; writing—review and editing, C.M.; visualization, M.B.; supervision, C.B.; project administration, C.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Provincia di Padova, Code CESC 5647/A0/23 Code URC AOP2940, 2 March 2023.

Informed Consent Statement

Informed consent was obtained from all subjects involved in this study.

Data Availability Statement

Data are available on demand.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
OPGOrthopantomography
CBCTCone Beam Computed Tomography
CTComputed Tomography
ZOLZoledronic acid
ALEAlendronate
IBAIbandronate

References

  1. Bedogni, A.; Mauceri, R.; Fusco, V.; Bertoldo, F.; Bettini, G.; Di Fede, O.; Lo Casto, A.; Marchetti, C.; Panzarella, V.; Saia, G.; et al. Italian Position Paper (SIPMO-SICMF) on Medication-Related Osteonecrosis of the Jaw (MRONJ). Oral Dis. 2024, 30, 3679–3709. [Google Scholar] [CrossRef] [PubMed]
  2. Khan, A.A.; Morrison, A.; Hanley, D.A.; Felsenberg, D.; McCauley, L.K.; O’Ryan, F.; Reid, I.R.; Ruggiero, S.L.; Taguchi, A.; Tetradis, S.; et al. Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus. J. Bone Miner. Res. 2015, 30, 3–23. [Google Scholar] [CrossRef] [PubMed]
  3. Nicolatou-Galitis, O.; Schiødt, M.; Mendes, R.A.; Ripamonti, C.; Hope, S.; Drudge-Coates, L.; Niepel, D.; Van den Wyngaert, T. Medication-related osteonecrosis of the jaw: Definition and best practice for prevention, diagnosis, and treatment. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2019, 127, 117–135. [Google Scholar] [CrossRef]
  4. Yarom, N.; Shapiro, C.L.; Peterson, D.E.; Van Poznak, C.H.; Bohlke, K.; Ruggiero, S.L.; Migliorati, C.A.; Khan, A.; Morrison, A.; Anderson, H.; et al. Medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J. Clin. Oncol. 2019, 37, 2270–2290. [Google Scholar] [CrossRef]
  5. Bedogni, A.; Fusco, V.; Agrillo, A.; Campisi, G. Learning from experience. Proposal of a refined definition and staging system for bisphosphonate-related osteonecrosis of the jaw (BRONJ). Oral Dis. 2012, 18, 621–623. [Google Scholar] [CrossRef] [PubMed]
  6. Campisi, G.; Mauceri, R.; Bertoldo, F.; Bettini, G.; Biasotto, M.; Colella, G.; Consolo, U.; Di Fede, O.; Favia, G.; Fusco, V.; et al. Medication-related osteonecrosis of the jaws (MRONJ) prevention and diagnosis: Italian consensus update 2020. Int. J. Environ. Res. Public Health 2020, 17, 5998. [Google Scholar] [CrossRef]
  7. Di Fede, O.; Panzarella, V.; Mauceri, R.; Fusco, V.; Bedogni, A.; Lo Muzio, L.; Sipmo Onj Board Campisi, G. The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention. Biomed. Res. Int. 2018, 2018, 2684924. [Google Scholar] [CrossRef]
  8. Ristow, O.; Otto, S.; Troeltzsch, M.; Hohlweg-Majert, B.; Pautke, C. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J. Cranio-Maxillofac. Surg. 2015, 43, 290–293. [Google Scholar] [CrossRef]
  9. Giudice, A.; Bennardo, F.; Barone, S.; Antonelli, A.; Figliuzzi, M.M.; Fortunato, L. Surgical management of medication-related osteonecrosis of the jaw: A systematic review. Int. J. Environ. Res. Public Health 2020, 17, 7560. [Google Scholar] [CrossRef]
  10. Aghaloo, T.; Hazboun, R.; Tetradis, S. Pathophysiology of osteonecrosis of the jaws and its management. Oral Maxillofac. Surg. Clin. N. Am. 2015, 27, 529–545. [Google Scholar] [CrossRef]
  11. Ikebe, T. Pathophysiology of BRONJ: Drug-related osteoclastic disease of the jaw. Oral Sci. Int. 2013, 10, 1–8. [Google Scholar] [CrossRef]
  12. Yang, G.; Singh, S.; Chen, Y.; Hamadeh, I.S.; Langaee, T.; McDonough, C.W.; Gong, Y.; Cooper-DeHoff, R.M.; Johnson, J.A. Pharmacogenomics of medication-related osteonecrosis of the jaw. Dent. Clin. N. Am. 2020, 64, 167–177. [Google Scholar] [CrossRef]
  13. Bae, S.; Sun, S.; Aghaloo, T.; Oh, J.E.; McKenna, C.E.; Kang, M.K.; Shin, K.H.; Tetradis, S.; Park, N.H.; Kim, R.H. Genetic factors associated with medication-related osteonecrosis of the jaw. Oral Dis. 2018, 24, 79–84. [Google Scholar] [CrossRef]
  14. Yazdi, P.M.; Schiodt, M. Dentoalveolar trauma and minor trauma as precipitating factors for medication-related osteonecrosis of the jaw (ONJ): A retrospective study of 149 consecutive patients from the Copenhagen ONJ Cohort. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2015, 119, 416–422. [Google Scholar] [CrossRef]
  15. Limones, A.; Sáez-Alcaide, L.M.; Díaz-Parreño, S.A.; Helm, A.; Bornstein, M.M.; Molinero-Mourelle, P. Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab vs. zoledronic acid: A systematic review and meta-analysis. Med. Oral Patol. Oral Cir. Bucal 2020, 25, e326–e336. [Google Scholar] [CrossRef]
  16. Dimopoulos, M.A.; Kastritis, E.; Bamia, C.; Melakopoulos, I.; Gika, D.; Roussou, M.; Migkou, M.; Eleftherakis-Papaiakovou, E.; Christoulas, D.; Terpos, E.; et al. The role of supportive care in the era of novel therapies for multiple myeloma. Ann. Hematol. 2015, 94 (Suppl. S1), S249–S258. [Google Scholar]
  17. Campisi, G.; Di Fede, O.; Musciotto, A.; Lo Casto, A.; Lo Muzio, L.; Fulfaro, F.; Buscemi, M.; Lo Russo, L.; Tomasello, L. Dental management in patients with bisphosphonates therapy. Dent. Cadmos 2007, 75, 1–28. [Google Scholar]
  18. Mauceri, R.; Panzarella, V.; Maniscalco, L.; Bedogni, A.; Licata, M.E.; Albanese, A.; Toia, F.; Cumbo, E.M.G.; Mazzola, G.; Di Fede, O.; et al. Conservative surgical treatment of bisphosphonate-related osteonecrosis of the jaw with Er,Cr:YSGG laser and platelet-rich plasma: A longitudinal study. Biomed. Res. Int. 2018, 2018, 3982540. [Google Scholar] [CrossRef]
  19. Blus, C.; Giannelli, G.; Szmukler-Moncler, S.; Orru, G. Ultrasonic bone surgery in the treatment of medication-related osteonecrosis of the jaws: A case series of 20 patients. Int. J. Periodontics Restor. Dent. 2017, 37, 821–829. [Google Scholar] [CrossRef]
  20. Vescovi, P.; Manfredi, M.; Merigo, E.; Meleti, M.; Fornaini, C.; Rocca, J.P.; Nammour, S. Surgical approach with Er:YAG laser on osteonecrosis of the jaws (ONJ) in patients under bisphosphonate therapy (BPT). Lasers Med. Sci. 2010, 25, 101–113. [Google Scholar] [CrossRef]
  21. Pavlíková, G.; Foltán, R.; Horká, M.; Hanzelka, T.; Borunská, H.; Sedý, J. Piezosurgery in oral and maxillofacial surgery. Int. J. Oral Maxillofac. Surg. 2011, 40, 451–457. [Google Scholar] [CrossRef] [PubMed]
  22. Curie, J.; Curie, P. Développement par compression de l’électricité polaire dans les cristaux hémièdres à faces inclinées. Comptes Rendus 1880, 91, 294–295. [Google Scholar] [CrossRef]
  23. Lippmann, G. Principe de la conservation de l’électricité. Ann. Chim. Phys. 1881, 24, 145–178. [Google Scholar]
  24. Manbachi, A.; Cobbold, R.S. Development and application of piezoelectric materials for ultrasound generation and detection. Ultrasound 2011, 19, 187–196. [Google Scholar] [CrossRef]
  25. Vercellotti, T. Technological characteristics and clinical indications of piezoelectric bone surgery. Minerva Stomatol. 2004, 53, 207–214. [Google Scholar] [PubMed]
  26. Eggers, G.; Klein, J.; Blank, J.; Hassfeld, S. Piezosurgery: An ultrasound device for cutting bone and its use and limitations in maxillofacial surgery. Br. J. Oral Maxillofac. Surg. 2004, 42, 451–453. [Google Scholar] [CrossRef]
  27. Pang, F.; Zhao, P.; Lee, H.Y.; Kim, D.J.; Meng, X.; Cho, Y.S.; Kim, S.W. Progress and Perspectives in 2D Piezoelectric Materials for Piezotronics and Piezo-Phototronics. Adv. Sci. 2025, 12, e2411422. [Google Scholar] [CrossRef]
  28. Stubinger, S.; Kuttenberger, J.; Filippi, A.; Sader, R.; Zeilhofer, H.F. Ultrasonic bone cutting in oral surgery: A review of 60 cases. Ultraschall Med. 2008, 29, 66–71. [Google Scholar] [CrossRef]
  29. Pereira, C.C.; Gealh, W.C.; Nogueira, L.M.; Garcia Junior, I.R.; Okamoto, R. Piezosurgery applied to implant dentistry: Clinical and biological aspects. J. Oral Implantol. 2014, 40, 401–408. [Google Scholar] [CrossRef]
  30. Robiony, M.; Polini, F.; Costa, F.; Vercellotti, T.; Politi, M. Piezoelectric bone cutting in multipiece maxillary osteotomies. J. Oral Maxillofac. Surg. 2004, 62, 759–761. [Google Scholar] [CrossRef]
  31. Sortino, F.; Pedullà, E.; Masoli, V. Piezoelectric device vs. conventional rotative instruments in impacted third molar surgery: Relationships between surgical difficulty and postoperative pain with histological evaluations. J. Cranio-Maxillofac. Surg. 2008, 36, 438–442. [Google Scholar] [CrossRef]
  32. Wu, Y.; Zou, J.; Tang, K.; Xia, Y.; Wang, X.; Song, L.; Wang, J.; Wang, K.; Wang, Z. From Electricity to Vitality: The Emerging Use of Piezoelectric Materials in Tissue Regeneration. Burn. Trauma 2024, 12, tkae013. [Google Scholar] [CrossRef] [PubMed]
  33. Preti, G.; Martinasso, G.; Peirone, B.; Navone, R.; Manzella, C.; Muzio, G.; Russo, C.; Canuto, R.A.; Schierano, G. Cytokines and growth factors involved in the osseointegration of oral titanium implants positioned using piezoelectric bone surgery versus a drill technique: A pilot study in minipigs. J. Periodontol. 2007, 78, 716–722. [Google Scholar] [CrossRef] [PubMed]
  34. Rahnama, M.; Czupkałło, Ł.; Czajkowski, L.; Grasza, J.; Wallner, J. The use of piezosurgery as an alternative method of minimally invasive surgery in the authors’ experience. Videosurgery Other Miniinvasive Tech. 2013, 8, 321–326. [Google Scholar] [CrossRef]
  35. Sivolella, S.; Brunello, G.; Berengo, M.; de Biagi, M.; Bacci, C. Rehabilitation with Implants After Bone Lid Surgery in the Posterior Mandible. J. Oral Maxillofac. Surg. 2015, 73, 1485–1492. [Google Scholar] [CrossRef]
  36. Rullo, R.; Piccirillo, A.; Femiano, F.; Nastri, L.; Festa, V.M. A Comparison between Piezoelectric Devices and Conventional Rotary Instruments in Bone Harvesting in Patients with Lip and Palate Cleft: A Retrospective Study with Clinical, Radiographical, and Histological Evaluation. Biomed. Res. Int. 2018, 2018, 2059464. [Google Scholar] [CrossRef]
  37. Schlee, M.; Steigmann, M.; Bratu, E.; Garg, A.K. Piezosurgery: Basics and possibilities. Implant Dent. 2006, 15, 334–340. [Google Scholar] [CrossRef]
  38. Blus, C.; Szmukler-Moncler, S.; Vozza, I.; Rispoli, L.; Polastri, C. Split-crest and immediate implant placement with ultrasonic bone surgery: A 3-year life-table analysis with 230 treated sites. Clin. Oral Implants Res. 2008, 19, 1139–1146. [Google Scholar] [CrossRef]
  39. Vercellotti, T.; De Paoli, S.; Nevins, M. The piezoelectric bony window osteotomy and sinus membrane elevation: Introduction of a new technique for simplification of the sinus augmentation procedure. Int. J. Periodontics Restor. Dent. 2001, 21, 561–567. [Google Scholar]
  40. Stübinger, S.; Kuttenberger, J.; Filippi, A.; Sader, R.; Zeilhofer, H.F. Intraoral piezosurgery: Preliminary results of a new technique. J. Oral Maxillofac. Surg. 2005, 63, 1283–1287. [Google Scholar] [CrossRef]
  41. Labanca, M.; Azzola, F.; Vinci, R.; Rodella, L.F. Piezoelectric Surgery: Twenty Years of Use. Br. J. Oral Maxillofac. Surg. 2008, 46, 265–269. [Google Scholar] [CrossRef] [PubMed]
  42. Campisi, G.; Mauceri, R.; Bertoldo, F.; Bettini, G.; Biasotto, M.; Colella, G.; Consolo, U.; Di Fede, O.; Favia, G.; Fusco, V.; et al. Italian Consensus Update on MRONJ Prevention in 2020. Int. J. Environ. Res. Public Health 2021, 18, 5345. [Google Scholar] [CrossRef]
  43. Ruggiero, S.L.; Dodson, T.B.; Aghaloo, T.; Carlson, E.R.; Ward, B.B.; Kademani, D. American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J. Oral Maxillofac. Surg. 2022, 80, 920–943. [Google Scholar] [CrossRef]
  44. World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 2013, 310, 2191–2194. [Google Scholar] [CrossRef]
  45. Von Elm, E.; Altman, D.G.; Egger, M.; Pocock, S.J.; Gøtzsche, P.C.; Vandenbroucke, J.P. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. J. Clin. Epidemiol. 2008, 61, 344–349. [Google Scholar] [CrossRef]
  46. Hoff, A.O.; Toth, B.B.; Altundag, K.; Johnson, M.M.; Warneke, C.L.; Hu, M.; Nooka, A.; Sayegh, G.; Guarneri, V.; Desrouleaux, K.; et al. Frequency and Risk Factors Associated with Osteonecrosis of the Jaw in Cancer Patients Treated with Intravenous Bisphosphonates. J. Bone Miner. Res. 2008, 23, 826–836. [Google Scholar] [CrossRef]
  47. Estilo, C.L.; van Poznak, C.H.; Williams, T.; Bohle, G.C.; Lwin, P.T.; Zhou, Q.; Riedel, E.R.; Carlson, D.L.; Schoder, H.; Farooki, A.; et al. Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate Therapy. Oncologist 2008, 13, 911–920. [Google Scholar] [CrossRef] [PubMed]
  48. Eckert, A.W.; Maurer, P.; Meyer, L.; Kriwalsky, M.S.; Rohrberg, R.; Schneider, D.; Bilkenroth, U.; Schubert, J. Bisphosphonate-Related Jaw Necrosis—Severe Complication in Maxillofacial Surgery. Cancer Treat. Rev. 2007, 33, 58–63. [Google Scholar] [CrossRef]
  49. Thumbigere-Math, V.; Tu, L.; Huckabay, S.; Dudek, A.Z.; Lunos, S.; Basi, D.L.; Hughes, P.J.; Leach, J.W.; Swenson, K.K.; Gopalakrishnan, R. A Retrospective Study Evaluating Frequency and Risk Factors of Osteonecrosis of the Jaw in 576 Cancer Patients Receiving Intravenous Bisphosphonates. Am. J. Clin. Oncol. 2012, 35, 386–392. [Google Scholar] [CrossRef]
  50. O’Ryan, F.S.; Lo, J.C. Bisphosphonate-Related Osteonecrosis of the Jaw in Patients with Oral Bisphosphonate Exposure: Clinical Course and Outcomes. J. Oral Maxillofac. Surg. 2012, 70, 1844–1853. [Google Scholar] [CrossRef]
  51. Fliefel, R.; Tröltzsch, M.; Kühnisch, J.; Ehrenfeld, M.; Otto, S. Treatment Strategies and Outcomes of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) with Characterization of Patients: A Systematic Review. Int. J. Oral Maxillofac. Surg. 2015, 44, 568–585. [Google Scholar] [CrossRef] [PubMed]
  52. Atalay, B.; Yalcin, S.; Emes, Y.; Aktas, I.; Aybar, B.; Issever, H.; Mandel, N.M.; Cetin, O.; Oncu, B. Bisphosphonate-Related Osteonecrosis: Laser-Assisted Surgical Treatment or Conventional Surgery? Lasers Med. Sci. 2011, 26, 815–823. [Google Scholar] [CrossRef] [PubMed]
  53. Vescovi, P.; Manfredi, M.; Merigo, E.; Meleti, M.; Guidotti, R.; Sarraj, A.; Mergoni, G.; Fornaini, C.; Bonanini, M.; Pizzi, S.; et al. Osteonecrosi dei Masscellari e Bisfosfonati: Terapia e Follow-Up a Lungo Periodo in 160 Pazienti. Dent. Cadmos 2012, 80, 9–21. [Google Scholar] [CrossRef]
  54. Thumbigere-Math, V.; Michalowicz, B.S.; Hodges, J.S.; Tsai, M.L.; Swenson, K.K.; Rockwell, L.; Gopalakrishnan, R. Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw. J. Periodontol. 2014, 85, 226–233. [Google Scholar] [CrossRef]
  55. Lorenzo-Pouso, A.I.; Pérez-Sayáns, M.; Chamorro-Petronacci, C.; Gándara-Vila, P.; López-Jornet, P.; Carballo, J.; García-García, A. Association Between Periodontitis and Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis. J. Oral Pathol. Med. 2020, 49, 190–200. [Google Scholar] [CrossRef]
  56. Dioguardi, M.; di Cosola, M.; Copelli, C.; Cantore, S.; Quarta, C.; Nitsch, G.; Sovereto, D.; Spirito, F.; Caloro, G.A.; Cazzolla, A.P.; et al. Oral Bisphosphonate-Induced Osteonecrosis Complications in Patients Undergoing Tooth Extraction: A Systematic Review and Literature Updates. Eur. Rev. Med. Pharmacol. Sci. 2023, 27, 6359–6373. [Google Scholar] [CrossRef]
  57. Nisi, M.; la Ferla, F.; Karapetsa, D.; Gennai, S.; Miccoli, M.; Baggiani, A.; Graziani, F.; Gabriele, M. Risk Factors Influencing BRONJ Staging in Patients Receiving Intravenous Bisphosphonates: A Multivariate Analysis. Int. J. Oral Maxillofac. Surg. 2015, 44, 586–591. [Google Scholar] [CrossRef]
  58. Bodem, J.P.; Kargus, S.; Eckstein, S.; Saure, D.; Engel, M.; Hoffmann, J.; Freudlsperger, C. Incidence of Bisphosphonate-Related Osteonecrosis of the Jaw in High-Risk Patients Undergoing Surgical Tooth Extraction. J. Cranio-Maxillofac. Surg. 2015, 43, 510–514. [Google Scholar] [CrossRef]
  59. Holzinger, D.; Seemann, R.; Matoni, N.; Ewers, R.; Millesi, W.; Wutzl, A. Effect of Dental Implants on Bisphosphonate-Related Osteonecrosis of the Jaws. J. Oral Maxillofac. Surg. 2014, 72, 1937.e1–1937.e8. [Google Scholar] [CrossRef]
  60. Levin, L.; Laviv, A.; Schwartz-Arad, D. Denture-related osteonecrosis of the maxilla associated with oral bisphosphonate treatment. J. Am. Dent. Assoc. 2007, 138, 1218–1220. [Google Scholar] [CrossRef]
  61. Hasegawa, Y.; Kawabe, M.; Kimura, H.; Kurita, K.; Fukuta, J.; Urade, M. Influence of dentures in the initial occurrence site on the prognosis of bisphosphonate-related osteonecrosis of the jaws: A retrospective study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012, 114, 318–324. [Google Scholar] [CrossRef] [PubMed]
  62. Yang, Y.-L.; Xiang, Z.-J.; Yang, J.-H.; Wang, W.-J.; Xiang, R.-L. The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: A systematic review and meta-analysis. Ther. Adv. Med. Oncol. 2019, 11, 1758835919855235. [Google Scholar] [CrossRef]
  63. Fung, P.L.; Nicoletti, P.; Shen, Y.; Porter, S.; Fedele, S. Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw. Oral Maxillofac. Surg. Clin. N. Am. 2015, 27, 537–546. [Google Scholar] [CrossRef]
  64. Apatzidou, D.A. The role of cigarette smoking in periodontal disease and treatment outcomes of dental implant therapy. In Periodontology 2000; John Wiley and Sons Inc.: Hoboken, NJ, USA, 2022; Volume 90, pp. 45–61. [Google Scholar] [CrossRef]
  65. Chambler, D.; Blincoe, T. Smoking and surgery. Br. J. Hosp. Med. 2018, 79, 478. [Google Scholar] [CrossRef] [PubMed]
  66. Bacci, C.; Boccuto, M.; Cerrato, A.; Grigoletto, A.; Zanette, G.; Angelini, A.; Sbricoli, L. Safety and efficacy of sectorial resection with piezoelectric device in ONJ. Qeios 2021. [Google Scholar]
  67. Shannon, J.; Shannon, J.; Modelevsky, S.; Grippo, A.A. Bisphosphonates and osteonecrosis of the jaw. J. Am. Geriatr. Soc. 2011, 59, 2350–2355. [Google Scholar] [CrossRef]
  68. Paek, S.J.; Park, W.-J.; Shin, H.-S.; Choi, M.-G.; Kwon, K.-H.; Choi, E.J. Diseases having an influence on inhibition of angiogenesis as risk factors of osteonecrosis of the jaw. J. Korean Assoc. Oral Maxillofac. Surg. 2016, 42, 271–277. [Google Scholar] [CrossRef]
  69. Molcho, S.; Peer, A.; Berg, T.; Futerman, B.; Khamaisi, M. Diabetes microvascular disease and the risk for bisphosphonate-related osteonecrosis of the jaw: A single center study. J. Clin. Endocrinol. Metab. 2013, 98, E1807–E1812. [Google Scholar] [CrossRef] [PubMed]
  70. Jarnbring, F.; Kashani, A.; Björk, A.; Hoffman, T.; Krawiec, K.; Ljungman, P.; Lund, B. Role of intravenous dosage regimens of bisphosphonates in relation to other aetiological factors in the development of osteonecrosis of the jaws in patients with myeloma. Br. J. Oral Maxillofac. Surg. 2015, 53, 1007–1011. [Google Scholar] [CrossRef]
  71. Anavi-Lev, K.; Anavi, Y.; Chaushu, G.; Alon, D.M.; Gal, G.; Kaplan, I. Bisphosphonate-related osteonecrosis of the jaws: Clinico-pathological investigation and histomorphometric analysis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2013, 115, 660–666. [Google Scholar] [CrossRef]
  72. Tiranathanagul, S.; Yongchaitrakul, T.; Pattamapun, K.; Pavasant, P. Actinobacillus actinomycetemcomitans Lipopolysaccharide activates matrix metalloproteinase-2 and increases receptor activator of nuclear factor-κB ligand expression in human periodontal ligament cells. J. Periodontol. 2004, 75, 1647–1654. [Google Scholar] [CrossRef] [PubMed]
  73. Jelin-Uhlig, S.; Weigel, M.; Ott, B.; Imirzalioglu, C.; Howaldt, H.-P.; Böttger, S.; Hain, T. Bisphosphonate-related osteonecrosis of the jaw and oral microbiome: Clinical risk factors, pathophysiology and treatment options. Int. J. Mol. Sci. 2024, 25, 8053. [Google Scholar] [CrossRef] [PubMed]
  74. Bennardo, F.; Barone, S.; Vocaturo, C.; Gheorghe, D.N.; Cosentini, G.; Antonelli, A.; Giudice, A. Comparison between Magneto-Dynamic, Piezoelectric, and Conventional Surgery for Dental Extractions: A Pilot Study. Dent. J 2023, 11, 60. [Google Scholar] [CrossRef]
  75. Blaskovic, M.; Gabrić, D.; Coleman, N.J.; Slipper, I.J.; Mladenov, M.; Gjorgievska, E. Bone Healing Following Different Types of Osteotomy: Scanning Electron Microscopy (SEM) and Three-Dimensional SEM Analyses. Microsc. Microanal. 2016, 22, 1170–1178. [Google Scholar] [CrossRef]
  76. Walia, S.; Verma, D.; Bansal, S.; Sutar, S.; Gupta, A.; Kardwal, K. Comparison of Piezosurgery Devices and the Use of Rotatory Devices for the Extraction of Impacted Mandibular Third Molars. J. Pharm. Bioallied Sci. 2024, 16 (Suppl. S3), S2140–S2142. [Google Scholar] [CrossRef]
  77. Franco, R.; Di Girolamo, M.; Franceschini, C.; Rastelli, S.; Capogreco, M.; D’Amario, M. The Comparative Efficacy of Burs Versus Piezoelectric Techniques in Third Molar Surgery: A Systematic Review Following the PRISMA Guidelines. Medicina 2024, 60, 2049. [Google Scholar] [CrossRef]
  78. Qadir, S.H.; Kheder, K.A.; Hassan, S.M.A. Histological assessment of potential inferior alveolar nerve injury following osteotomy of the mandibular buccal cortex using a piezoelectric saw. Cell. Mol. Biol. 2024, 70, 44–49. [Google Scholar] [CrossRef] [PubMed]
  79. Seluki, R.; Seluki, M.; Vaitkeviciene, I.; Jagelaviciene, E. Comparison of the effectiveness of conservative and surgical treatment of medication-related osteonecrosis of the jaw: A systematic review. J. Oral Maxillofac. Res. 2023, 14, e1. [Google Scholar] [CrossRef]
  80. Beth-Tasdogan, N.H.; Mayer, B.; Hussein, H.; Zolk, O.; Peter, J.U. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst. Rev. 2022, 2022, CD012432. [Google Scholar] [CrossRef]
  81. Di Fede, O.; Canepa, F.; Panzarella, V.; Mauceri, R.; Bedogni, A.; Lo Muzio, L.; Campisi, G. The treatment of medication-related osteonecrosis of the jaw (MRONJ): A systematic review with a pooled analysis of only surgery versus combined protocols. Int. J. Environ. Res. Public Health 2021, 18, 8432. [Google Scholar] [CrossRef]
  82. Miksad, R.A.; Lai, K.-C.; Dodson, T.B.; Woo, S.-B.; Treister, N.S.; Akinyemi, O.; Bihrle, M.; Maytal, G.; August, M.; Gazelle, G.S.; et al. Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw. Oncologist 2011, 16, 121–132. [Google Scholar] [CrossRef]
  83. Blus, C.; Szmukler-Moncler, S.; Giannelli, G.; Denotti, G.; Orrù, G. Use of ultrasonic bone surgery (Piezosurgery) to surgically treat bisphosphonate-related osteonecrosis of the jaws (BRONJ): A case series report with at least 1 year of follow-up. Open Dent. J. 2013, 7, 94–101. [Google Scholar] [CrossRef] [PubMed]
  84. Blus, C.; Giannelli, G.; Szmukler-Moncler, S.; Orrù, G. Treatment of medication-related osteonecrosis of the jaws (MRONJ) with ultrasonic piezoelectric bone surgery: A case series of 20 treated sites. Oral Maxillofac. Surg. 2017, 21, 41–48. [Google Scholar] [CrossRef]
  85. Dipalma, G.; Inchingolo, A.M.; Malcangi, G.; Ferrara, I.; Viapiano, F.; Netti, A.; Patano, A.; Isacco, C.G.; Inchingolo, A.D.; Inchingolo, F. Sixty-month follow-up of clinical MRONJ cases treated with CGF and piezosurgery. Bioengineering 2023, 10, 863. [Google Scholar] [CrossRef] [PubMed]
  86. Bacci, C.; Maglione, M.; Favero, L.; Perini, A.; Di Lenarda, R.; Berengo, M.; Zanon, E. Management of dental extraction in patients undergoing anticoagulant treatment: Results from a large, multicentre, prospective, case-control study. Thromb. Haemost. 2010, 104, 972–975. [Google Scholar] [CrossRef] [PubMed]
  87. Bacci, C.; Berengo, M.; Favero, L.; Zanon, E. Safety of dental implant surgery in patients undergoing anticoagulation therapy: A prospective case-control study. Clin. Oral Implant. Res. 2011, 22, 151–156. [Google Scholar] [CrossRef]
  88. Bacci, C.; Schiazzano, C.; Zanon, E.; Stellini, E.; Sbricoli, L. Bleeding disorders and dental implants: Review and clinical indications. J. Clin. Med. 2023, 12, 4757. [Google Scholar] [CrossRef]
  89. Bacci, C.; Cerrato, A.; Bardhi, E.; Frigo, A.C.; Djaballah, S.A.; Sivolella, S. A retrospective study on the incidence of medication-related osteonecrosis of the jaws (MRONJ) associated with different preventive dental care modalities. Support. Care Cancer 2022, 30, 1723–1729. [Google Scholar] [CrossRef]
  90. Dawiec, G.; Niemczyk, W.; Wiench, R.; Niemczyk, S.; Skaba, D. Introduction to amniotic membranes in maxillofacial surgery—A scoping review. Medicina 2024, 60, 663. [Google Scholar] [CrossRef]
  91. Manani, G.; Bacci, C.; Zanette, G.; Facco, E. Stato attuale della sedazione cosciente in odontoiatria [Contemporary state of sedation in dentistry]. Dent. Cadmos 2012, 80, 357–369. [Google Scholar] [CrossRef]
  92. Niemczyk, W.; Żurek, J.; Niemczyk, S.; Kępa, M.; Zięba, N.; Misiołek, M.; Wiench, R. Antibiotic-Loaded Platelet-Rich Fibrin (AL-PRF) as a New Carrier for Antimicrobials: A Systematic Review of In Vitro Studies. Int. J. Mol. Sci. 2025, 26, 2140. [Google Scholar] [CrossRef] [PubMed]
Figure 1. (A) Clinical case BRONJ stage 1b with osteonecrosis in the right mandible. Preoperative radiograph (T0). (B) Intra-oral clinical picture (T0) with distal bone exposure at second lower right premolar.
Figure 1. (A) Clinical case BRONJ stage 1b with osteonecrosis in the right mandible. Preoperative radiograph (T0). (B) Intra-oral clinical picture (T0) with distal bone exposure at second lower right premolar.
Jcm 14 03792 g001
Figure 2. (A) Full thickness surgical flap detachment; (B) Piezoelectric device osteotomy lines; (C) Completion of osteotomy; (D) Clinical picture after resection; (E) Tissue removed with second lower right premolar and implant seat in first lower right molar position; (F) Suture and closure by primary intention.
Figure 2. (A) Full thickness surgical flap detachment; (B) Piezoelectric device osteotomy lines; (C) Completion of osteotomy; (D) Clinical picture after resection; (E) Tissue removed with second lower right premolar and implant seat in first lower right molar position; (F) Suture and closure by primary intention.
Jcm 14 03792 g002
Figure 3. (A) Clinical picture 12 months after surgery (T3); (B) Radiography 12 months after piezoelectric surgery (T3).
Figure 3. (A) Clinical picture 12 months after surgery (T3); (B) Radiography 12 months after piezoelectric surgery (T3).
Jcm 14 03792 g003
Table 1. Inclusion and exclusion criteria.
Table 1. Inclusion and exclusion criteria.
Inclusion Criteria Exclusion Criteria
-
Adult patients who took only bisphosphonates, not other MRONJ-related drugs, with BRONJ stages 1 and 2, undergoing marginal resection with piezoelectric devices
-
Patients followed by the same surgeon for both visits and surgery
-
Availability of clinical documentation
-
Patients underwent three follow-up visits at 1 month (T1), 6 months (T2), and 12 months (T3) post-surgery
-
Patients who had undergone head and neck radiotherapy
-
Patients who took non-bisphosphonates drugs and developed MRONJ
-
Patients with primary or metastatic neoplasms of the maxillary bones
Table 2. Clinical and radiographic stages of Medication-Related Osteonecrosis of the Jaw (MRONJ) based on SIPMO-SICMF staging criteria [1].
Table 2. Clinical and radiographic stages of Medication-Related Osteonecrosis of the Jaw (MRONJ) based on SIPMO-SICMF staging criteria [1].
StageClinical Signs and Symptoms CT Signs
Stage 1—Focal Mronj
The presence of at least 1 clinical sign/symptom and increased bone density limited to the alveolar process at CT, with or without additional radiological signs.
-
Stage 1a: Asymptomatic (without pain)
-
Stage 1b: Symptomatic (the presence of pain and/or purulent discharge)
Abscess, bone exposure, halitosis, intraoral fistula, jaw pain of bone origin, mucosal inflammation, non-healing post-extraction socket, soft tissue swelling, spontaneous loss of bone fragments, sudden dental/implant mobility, purulent discharge, toothache and trismus.Trabecular thickening and/or focal bone marrow sclerosis, with or without cortical erosion, osteolytic changes, thickening of the alveolar ridge, thickening of the lamina dura, persistent post-extraction socket, periodontal space widening, thickening of the inferior alveolar nerve canal, sequester formation.
Stage 2—Diffuse Mronj
The presence of at least 1 clinical sign/symptom and increased bone density extending to the basal bone at CT, with or without additional radiological signs.
-
Stage 2a: asymptomatic (without pain)
-
Stage 2b: symptomatic (presence of pain and/or purulent discharge)
Same as Stage 1, plus mandibular deformation and numbness of the lips.Diffuse bone marrow sclerosis, with or without cortical erosion, osteolytic changes, thickening of the alveolar ridge, thickening of the lamina dura, persistent post-extraction socket, periodontal space widening, thickening of the inferior alveolar nerve canal, sequester formation, periosteal reaction, and opacified maxillary sinus.
Stage 3—Complicated Mronj
The presence of at least 1 clinical sign/symptom and increased bone density extended to the basal bone at CT, plus one or more of the following
-
Stage 3a: asymptomatic (without pain)
-
Stage 3b: symptomatic (presence of pain and/or purulent discharge)
Cutaneous fistula, mandible fracture, fluid discharge from the nose.Osteosclerosis of adjacent bones (zygoma and hard palate), pathologic fracture, osteolysis extending to the maxillary sinus, sinus tract (oroantral, oronasal fistula, oro-cutaneous).
Table 3. Clinical and radiographic stages of Medication-Related Osteonecrosis of the Jaw (MRONJ) based on AAOMS staging criteria [43].
Table 3. Clinical and radiographic stages of Medication-Related Osteonecrosis of the Jaw (MRONJ) based on AAOMS staging criteria [43].
Stage Symptoms Clinical Findings Radiographic Findings
Stage 0
-
Odontalgia not explained by an odontogenic cause.
-
Dull, aching bone pain in the jaw, which may radiate to the temporomandibular joint region.
-
Sinus pain, which may be associated with inflammation and thickening of the maxillary sinus wall.
-
Altered neurosensory function.
-
Loosening of teeth not explained by chronic periodontal disease.
-
Intraoral or extraoral swelling.
-
Alveolar bone loss or resorption not attributable to chronic periodontal disease.
-
Changes to trabecular pattern sclerotic bone and no new bone in extraction sockets.
-
Regions of osteosclerosis involving the alveolar bone and/or the surrounding basilar bone.
-
Thickening/obscuring of periodontal ligament (thickening of the lamina dura, sclerosis, and decreased size of the periodontal ligament space).
Stage I
-
Asymptomatic
-
Exposed and necrotic bone or fistula that probes to the bone.
-
No evidence of infection/inflammation.
-
May present with radiographic findings mentioned for Stage 0 that are localized to the alveolar bone region.
Stage II
-
Symptomatic
-
Exposed and necrotic bone, or fistula that probes to the bone.
-
Evidence of infection/inflammation.
-
May present with radiographic findings mentioned for Stage 0 localized to the alveolar bone region.
Stage III
-
Symptomatic
-
Exposed and necrotic bone or fistulae that probes to the bone.
-
Evidence of infection.
-
One or more of the following:
Exposed necrotic bone extending beyond the region of alveolar bone (i.e., inferior border and ramus in the mandible, maxillary sinus, and zygoma in the maxilla).
Extraoral fistula.
Oral antral/oral–nasal communication.
-
May be present:
Pathologic fracture.
Osteolysis extending to the inferior border of the mandible or sinus floor.
Table 4. Distribution of patients based on clinical signs and symptoms of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) recorded preoperatively (T0).
Table 4. Distribution of patients based on clinical signs and symptoms of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) recorded preoperatively (T0).
Clinical Signs and Symptoms of BRONJ (T0)N° of Patients%
Exposed bone21100
Halitosis1152.38
Dental mobility733.33
Pain628.57
Trismus523.81
Failure of post-extraction alveolar mucosa repair419.05
Soft tissue swelling314.29
Lip paresthesia/dysesthesia314.29
Implant mobility29.52
Suppuration29.52
Table 5. Distribution of patients based on radiographic signs of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) recorded preoperatively (T0).
Table 5. Distribution of patients based on radiographic signs of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) recorded preoperatively (T0).
Radiographic Signs of BRONJ (T0)N° of Patients%
Diffuse osteosclerosis628.57
Focal medullary osteosclerosis523.81
Widening of the periodontal space523.81
Persistence of post-extraction alveolus419.05
Sinusitis419.05
Thickening of the alveolar canal29.52
Oro-antral fistulas29.52
Periosteal reaction29.52
Table 6. Operative time values evaluated in minutes for each patient, mean, median, and standard deviation evaluation in minutes.
Table 6. Operative time values evaluated in minutes for each patient, mean, median, and standard deviation evaluation in minutes.
No. of PatientsPercentage (%)Operative Time (min)Mean (min)Median (min)Standard Deviation (min)
Total
(21 patients)
100% 48.81458.98
14.76%75
314.29%60
314.29%55
942.86%45
523.81%40
Table 7. Clinical cases and corresponding clinical-radiographic signs and symptoms of BRONJ observed after piezoelectric marginal resection at follow-up (T1-T2-T3).
Table 7. Clinical cases and corresponding clinical-radiographic signs and symptoms of BRONJ observed after piezoelectric marginal resection at follow-up (T1-T2-T3).
N° PatientT1 Clinical Signs and Symptoms of BRONJT1 Radiographic Signs of BRONJT2 Clinical Signs and Symptoms of BRONJT2 Radiographic Signs of BRONJT3 Clinical Signs and Symptoms of BRONJT3 Radiographic Signs of BRONJ
1Incomplete epithelialization, DysesthesiaX-rays not performedIncomplete epithelialization, DysesthesiaTrabecular thickeningExposed bone, Dysesthesia, PainFocal medullary osteosclerosis
8Incomplete epithelializationX-rays not performedAbsentAbsentAbsentAbsent
13Incomplete epithelialization, TrismusX-rays not performedAbsentAbsentAbsentAbsent
14Incomplete epithelializationX-rays not performedAbsentAbsentAbsentAbsent
19Incomplete epithelialization, Lip DysesthesiaX-rays not performedAbsentAbsentAbsentAbsent
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Manera, C.; Tessari, M.L.; Boccuto, M.; Bacci, C. Clinical Effectiveness of Surgical Marginal Resection with Piezoelectric Device on Bisphosphonate-Related Osteonecrosis of the Jaws: A Retrospective Study. J. Clin. Med. 2025, 14, 3792. https://doi.org/10.3390/jcm14113792

AMA Style

Manera C, Tessari ML, Boccuto M, Bacci C. Clinical Effectiveness of Surgical Marginal Resection with Piezoelectric Device on Bisphosphonate-Related Osteonecrosis of the Jaws: A Retrospective Study. Journal of Clinical Medicine. 2025; 14(11):3792. https://doi.org/10.3390/jcm14113792

Chicago/Turabian Style

Manera, Claudia, Martina Lee Tessari, Mariagrazia Boccuto, and Christian Bacci. 2025. "Clinical Effectiveness of Surgical Marginal Resection with Piezoelectric Device on Bisphosphonate-Related Osteonecrosis of the Jaws: A Retrospective Study" Journal of Clinical Medicine 14, no. 11: 3792. https://doi.org/10.3390/jcm14113792

APA Style

Manera, C., Tessari, M. L., Boccuto, M., & Bacci, C. (2025). Clinical Effectiveness of Surgical Marginal Resection with Piezoelectric Device on Bisphosphonate-Related Osteonecrosis of the Jaws: A Retrospective Study. Journal of Clinical Medicine, 14(11), 3792. https://doi.org/10.3390/jcm14113792

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop