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The aim of this article is to report the results obtained by the use of HAM in surgical wound healing and the reduction of relapse in patients affected by Medication-related osteonecrosis of the jaw (MRONJ).The study involved patients with the diagnosis of MRONJ, surgically treated between October 2016 and April 2019, in a case–control setting. Enrolled patients were randomly divided into 2 groups. One group will be treated with resective surgery and with the insertion of HAM patch (Group A), while the second group had been treated exclusively with resective surgery (Group B).The patients underwent MRONJ surgical treatment with the placement of amniotic membrane patches at the wound site. Data regarding the long-term complications/functions were evaluated at 3, 6, 12, and 24 months after surgery. Pain measurements were performed before the intervention (T0), 7(T1) and 30(T2) days after surgery. 49 patients were included in the study. 2 patients of GROUP A after 30 days since they were surgically treated showed persistent bone exposure. 5 patients of group B demonstrated a lack of healing of the surgical wound with the persistence of bone exposed to 30 days after surgery. Statistical analysis ruled out any difference in OUTCOME (relapse) between GROUP A and B (p = 0.23). However, the Fisher test highlighted a significant difference between the use of HAM and only surgical treatment in pain at rest (p = 0.032). The use of amniotic membrane implement the patient's quality of life and reduce pain perception. has a learning curve that is fast enough to justify its routine use.

Bisphosphonates (BSPs) are used for the treatment of multiple myeloma, metastatic breast and lung cancer, Paget's disease, osteoporosis, hypercalcemia due to malignancy, and many other skeletal diseases. BSPs reduce osteoclastic functions, which result in bone resorption. Bisphosphonates-related osteonecrosis of jaws (BRONJ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates. BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue. There is currently no consensus on the correct approach to this issue. The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic. BRONJ was evaluated in patients with lung, prostate, and breast cancer under intravenous BSP treatment. Twenty patients in this study developed mandibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously. Bone turnover rates were evaluated by serum terminal C-telopeptide levels (CTX) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy. Ten patients were treated with laser surgery and biostimulation. An Er:YAG laser (Fotona Fidelis Plus II® Combine laser equipment, Slovenia) very long pulse (VLP) mode (200 mJ, 20 Hz) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis. Biostimulation was applied postoperatively using an Nd:YAG laser. Low-level laser therapy (LLLT) was applied to the tissues for 1 min from 4 cm distance using an Nd:YAG laser (Fotona-Slovenia) with a R24 950-µm fiber handpiece long-pulse (LP) mode, 0.25-W, 10 Hz power/cm 2 from the mentioned distance the spot size was 0.4 cm 2 , and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm 2 . The other ten patients were treated with conventional surgery. Treatment outcomes were noted as either complete healing or incomplete healing. There were no statistically significant differences between laser surgery and conventional surgery ( p  > 0.05). CTX values also did not affect the prognosis of the patients. Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis. Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ. Laser surgery is a beneficial alternative in the treatment of patients with this situation. Further randomized studies with larger patient numbers may also improve our understanding of treatment protocols for this situation.

This retrospective study evaluated changes in lesion bone density and volume in medication-related osteonecrosis of the jaw (MRONJ) using cone-beam computed tomography (CBCT) at different disease stages following conservative and surgical treatment. Additionally, the study analyzed the correlations between these changes and influencing factors. A total of 54 patients (mean [SD] age, 75.43 [7.44] years) diagnosed with stage 0, 1, 2, or 3 MRONJ, according to the American Association of Oral and Maxillofacial Surgeons’ guidelines, were included. Pre- and post-treatment CBCT images were superimposed to identify the lesion locations, and lesions were segmented manually using ITK-SNAP software. Lesion mean bone density and volume before and after treatment were calculated. Stage 0–1 lesions showed a 16.8% reduction in bone density and a 17.0% reduction in volume and, while stage 2–3 lesions exhibited a 20.8% increase in bone density and a 46.0% reduction in volume ( P  < 0.05). In conclusion, stage 2–3 lesions demonstrated better healing outcomes than stage 0–1 lesions. Notably, conservative treatment may potentially benefit from a longer drug holiday, while surgical treatment showed positive effects on both soft and hard tissues in stage 2–3 lesions, regardless of the drug holiday duration.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007–2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comparing combined conservative surgery versus only aggressive (91% versus 72%, p = 0.05), was observed. No significant difference regarding any group with respect to the 6-month total resolution rate (82% versus 72%) was demonstrated. Of note, conservative surgery combined with various, adjuvant, non-invasive procedures (ozone, LLLT or blood component + Nd:YAG) was found to achieve partial or full healing in all stages, with improved results and the amelioration of many variables. In conclusion, specific adjuvant treatments associated with minimally conservative surgery can be considered effective and safe in the treatment of MRONJ, although well-controlled studies are a requisite in arriving at definitive statements

Background The purpose of this study was to evaluate the outcomes of alveoplasty and primary closure following dental extractions in patients with an elevated medication-related osteonecrosis of the jaw (MRONJ) risk. Study design A retrospective review of 46 patients with an elevated MRONJ risk was conducted. This included a total of 124 teeth extracted, due to unrestorable caries (n = 46; 37%) and peri-apical pathology (n = 44; 35%). Results Our results showed 0% (n = 0) of patients in our cohort developed MRONJ post-operatively. Most patients were being treated with intravenous zoledronic acid for breast cancer (n = 23; 50%), with an average of 15 doses (range 1-72). Conclusions This study supports the use of alveoplasty and primary closure for patients with an elevated MRONJ risk. The authors highlight the importance of pre-operative cone beam computed tomography imaging, optimisation of immune status, post-operative prophylactic antibiotics, and the delay of bone modifying agents recommencement as influential factors in mitigating risk and favouring successful outcomes. Key points Patients considered to have an ‘elevated risk of medication-related osteonecrosis of the jaw' can undergo dental extraction with <1% overall risk. Excluding pre-existing medication-related osteonecrosis of the jaw before dental extraction via cone beam computed tomography is a key pre-operative step. Highlights that mucosal flaps and bone removal are important steps to achieve healing rather than the non-evidence belief that it is contraindicated.

IntroductionSurgery is the standard treatment for medication-related osteonecrosis of the jaw (MRONJ). This study reviewed patients with mandibular MRONJ who underwent surgical treatment, and in particular the characteristics of non-osteolytic MRONJ with no evidence of osteolysis on CT were described.Materials and methodsWe conducted a retrospective study of patients with mandibular MRONJ who underwent surgery between January 2016 and September 2022. Various clinical and imaging factors regarding treatment outcomes were investigated and analyzed. Additionally, the disease course of non-osteolytic MRONJ was examined in detail.ResultsThis study included 55 patients (66 surgeries) with a mean age of 74.7. The primary disease was osteoporosis (24 patients) and malignancy (31 patients); the type of antiresorptive agent was bisphosphonate (BP) in 21 patients and denosumab (DMB) in 26. BP was initially administered; however, it was changed to DMB in eight patients. Preoperatively, the cumulative cure rates for all 66 surgeries were 72.8% at 1 year and 77.3% at 2 years. Cure rates were significantly lower in patients with malignancy, those without osteolysis, and those who underwent sequestrum removal or marginal mandibulectomy than those with osteoporosis, osteolysis, and segmental mandibulectomy. Non-osteolytic MRONJ was observed in eight patients, all with malignancy and receiving high-dose DMB. Only two patients were cured after the initial surgery, and most patients ultimately underwent segmental mandibulectomy.ConclusionsSurgical treatment yielded good treatment outcomes in most patients with mandibular MRONJ; however, the cure rate was lower in patients with malignancy who showed no osteolysis on CT images.

SummaryOsteonecrosis of the jaw (ONJ) is rare (2.53/10,000 person-years) among alendronate users, but long-term and compliant use are associated with an increased risk of surgically treated ONJ. Risk of surgically treated ONJ is higher in patients with rheumatoid diseases and use of proton pump inhibitors.IntroductionONJ is a rare event in users of oral bisphosphonates. Our aims were to evaluate if the risk of surgically treated ONJ increases with longer or more compliant treatment with alendronate for osteoporosis and to identify risk factors for surgically treated ONJ.MethodsOpen nationwide register-based cohort study containing one nested case-control study. Patients were treatment-naïve incident users of alendronate 1996–2007 in Denmark, both genders, aged 50–94 at the time of beginning treatment (N = 61,990). Participants were followed to 31 December 2013.ResultsOver a mean of 6.8 years, 107 patients received surgery for ONJ or related conditions corresponding to an incidence rate of 2.53 (95% confidence interval (CI) 2.08 to 3.05) per 10,000 patient years. Recent use was associated with an adjusted odds ratio (OR) 4.13 (95% CI 1.94 to 8.79) compared to past use. Similarly, adherent users (medication possession ratio (MPR) >50%) were at two to threefold increased risk of ONJ compared to low adherence (MPR <50%), and long-term (>5 years) use was related with higher risk (adjusted OR 2.31 (95% CI (1.14 to 4.67)) than shorter-term use. History of rheumatoid disorders and use of proton pump inhibitors were independently associated with surgically treated ONJ.ConclusionsOur data suggest that recent, long-term, and compliant uses of alendronate are associated with an increased risk of surgically treated ONJ. Nevertheless, the rates remain low, even in long-term adherent users. ONJ risk appears higher in patients with conditions likely to indirectly affect the oral mucosa.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event induced by antiresorptive agents (ARAs). The purpose of this study was to evaluate variables, mainly surgery and hyperbaric oxygen (HBO) therapy, associated with treatment outcomes in patients with a diagnosis of ARONJ at a single center. We enrolled consecutive patients who presented to our hospital for the management of stage 2 or 3 ARONJ between January 2003 and December 2019. The relationship between potentially predictive factors and outcome variables was examined using statistical analyses, along with a subgroup analysis based on disease stage. Of 252 patients included in this study, 206 had stage 2 ARONJ and 46 had stage 3 ARONJ. There were 119 patients with osteoporosis and 133 with malignant disease. In total, 139 patients were healed, and the healing rate of patients with stage 3 ARONJ was lower than that of patients with stage 2 ARONJ. With regard to the combination of surgery and HBO therapy, most patients underwent HBO before and after surgery. In the univariable analysis, surgery showed a therapeutic effect in both stage 2 and 3 ARONJ, whereas HBO showed a therapeutic effect in stage 2 ARONJ. In the multivariable analysis for stage 2 ARONJ, extensive surgery showed a stronger association with healing than conservative surgery, whereas ≥46 sessions of HBO therapy was less associated with healing than was non-HBO therapy. Our findings suggest that extensive surgery is highly effective against ARONJ regardless of disease stage if there is a sequestrum separation and systemic tolerance, whereas HBO therapy before and after surgical approach can be effective. Further studies are needed to identify treatment strategies for patients with treatment-refractory ARONJ who may be forced to undergo long-term HBO therapy with the expectation of sequestrum separation.

Objectives To provide an overview of the features of patients with medication-related osteonecrosis of the jaw (MRONJ) and explore recurrence-related factors after surgery. Materials and methods All pathological records of patients diagnosed with osteonecrosis or osteomyelitis of the jaw were reviewed. Only patients who had a history of use of medication related to bone turnover were included. All demographic and clinical characteristics were collected during review. Univariate and logistic regression analyses were performed to evaluate the associations between risk factors and recurrence. A p value < 0.05 was considered to indicate statistical significance in all analyses. Results A total of 313 patients were ultimately included. Most patients (89.14%) underwent bone turnover-related treatment due to malignancy. The breast and prostate were the most common locations of primary tumors in females and males, respectively. Almost all MRONJ patients experienced inflammatory symptoms. Recurrence occurred in 55 patients at 60 locations. The total recurrence rate was 16.85%, with no significant differences between the maxilla and mandible. Extensive surgery and flap transfer were strongly related to a lower recurrence risk. Nearly 80% of patients had recurrence-related symptoms within 6 months. Conclusion When MRONJ is treated with surgical methods, extensive resection and flap transfer can reduce recurrence risk. Six-month follow-up is needed to exclude recurrence after surgery. Clinical relevance This study revealed the surgical-related risk factors, such as extensive surgery and flap transfer, when treating MRONJ patients, and 6-month follow-up is needed to detect recurrence. This could provide clinical guidance for head and neck surgeons.

IntroductionSurgical treatment in patients with medication-related osteonecrosis of the jaw (MRONJ) is superior to conservative treatment. However, treatment outcome in patients with periosteal reaction (PR) was significantly poorer than that of those without PR. The purpose of this retrospective study was to analyze the pathophysiology and clinical significance of PR in MRONJ.Materials and methodsOut of 181 patients with MRONJ undergoing surgery, 38 patients with PR were enrolled in the study. CT examinations, histological examinations, and bacteriological examinations using real-time polymerase chain reaction were performed, and the relationship among the opted surgical method, CT findings, and treatment outcome was investigated.ResultsThe pattern of PR was classified into three types: 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. Histological examinations revealed inflammatory tissue in the area visualized as a gap on CT. Bacteriological examination showed the presence of bacteria in the type 2 or type 3 PR. Complete cure was observed in 21 of 38 (55.3%) patients, which was lower than the cure rate of 73.4% in 143 patients without PR. The cure rate was significantly lower in cases with type 3 PR or with persistent osteolysis.ConclusionsIt seems that complete resection of both osteolytic area and type 3 PR is necessary to obtain complete healing in patients undergoing marginal mandibulectomy.