The Effect of Er:YAG Laser Therapy as an Adjunct to Surgical Treatment Compared to Latter Alone in Managing Medication-Related Osteonecrosis of the Jaw: A Randomised Controlled Clinical Trial.

Introduction

Advancements in pharmacology and the introduction of newer drug generations could potentially lead to adverse effects and/or complications. 1 Medication-related osteonecrosis of the jaw (MRONJ) has been associated with various groups of drugs such as bisphosphonates (BSs). 2 , 3 , 4 BS are widely used in patients with breast or prostate cancer, multiple myeloma, and osteoporosis. 5 , 6 , 7 , 8 Consequently, individuals from these patient groups face an elevated risk of developing MRONJ, particularly when BSs are administered intravenously. 9 , 10 , 11

MRONJ is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) based on 3 overlapping clinical criteria: (1) current or prior treatment with antiresorptive therapy, either alone or in combination with immunomodulators or antiangiogenic drugs; (2) exposed bone or bone that can be probed through intraoral or extraoral fistulas in the maxillofacial region persisting longer than 8 weeks; and (3) no history of jaw radiotherapy or metastatic disease in the jaw. 12 , 13 , 14 , 15 , 16

In addition to BSs, drugs that may contribute to MRONJ include denosumab, a receptor activator of nuclear factor kappa-B ligand inhibitor. Denosumab is an antiresorptive agent administered subcutaneously, intravenously, or orally, primarily for the treatment of osteoporosis, 17 , 18 , 19 as well as antianiogenic medications used to prevent the growth of new blood vessels that feed tumours. 20 , 21 , 22 , 23

In the literature and AAOMS recommendations, stages I and II of MRONJ are traditionally managed conservatively, with surgical procedures reserved for stage III cases. However, current perspectives suggest that surgical treatment offers the most favourable outcomes across all stages of disease advancement. With the development of surgical techniques, laser-assisted surgery has emerged as a promising option worth further exploration. 24 , 25 , 26 The benefits of using a laser include a reduced risk of infection, less pain and swelling, faster healing, and high precision by focusing on a small area. It also allows for the removal of dental prosthesis supra-structures preoperatively, improving access to the surgical field. 27 , 28 , 29 , 30 , 31 The Er:YAG laser significantly enhances treatment outcomes, providing more stable results compared to classical surgical methods. 32 A key advantage of the Er:YAG laser, with its 2940-nm wavelength, is its high absorption in water-containing bone tissue, making it particularly effective. Following laser application, the bone surface is decontaminated, microbiologically clean, and free of a smear layer. 33 , 34 , 35 The literature increasingly highlights the beneficial effect of photobiomodulation, also known as low-level laser therapy, in treating early stages of MRONJ. 36 , 37 , 38 , 39 , 40 , 41 , 42

The aim of the study is to compare the effect of surgical treatment alone versus surgical treatment combined with adjunctive Er:YAG laser therapy on postoperative complication rates, pain, and mucosal healing in patients diagnosed with MRONJ.

Materials and methods

Study design

This study was an interventional randomised clinical trial that took place at the Department of Dental Surgery of the Medical University of Wroclaw, Poland. The study was registered at Clinicaltrials.gov (ID NCT07029815 ).

Ethical approval

The treatment options, including the advantages and disadvantages of surgery alone or surgery combined with laser therapy, were explained to patients, and consent forms were obtained from all participants involved in the study. The clinical trial was conducted according to the Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board and Ethics Committee of Wroclaw Medical University on January 29, 2021 (Bioethics Committee agreement No. KB-27/2021). Data were treated to ensure the confidentiality and privacy of patients.

Sampling technique

A total of 106 patients diagnosed with MRONJ participated in the study comparing treatment outcomes of conventional surgery versus Er:YAG laser-assisted surgery. The sample was a nonprobability, convenience, consecutive sample. Patients were allocated into 2 groups, a control group (n = 36) and a test group (n = 36), randomly using a software-generated random table, and allocation concealment was ensured using sealed envelopes.

Inclusion and exclusion criteria

Patients included in the study had a confirmed diagnosis of MRONJ, defined as the presence of exposed bone or bone that could be probed through a fistula in the maxillofacial region, persisting for more than 8 weeks, with a history of antiresorptive or antiangiogenic treatment and no history of radiotherapy to the jaws. Exclusion criteria included a history of head and neck radiotherapy and systemic conditions requiring hospitalisation, such as poor general health (American Society of Anesthesiologists grade III and IV).

Blinding

The study was set up as a double-blind randomised clinical trial. The procedures were performed by FM who was not blinded to the procedure. However, patients, as well as the clinician who evaluated the postoperative outcomes and HA who analysed the data, were all blinded to the procedure.

Preoperative management

All patients had panoramic radiographs during the initial diagnostic stage. Cone-beam computed tomography was performed prior to surgery to precisely assess the extent of necrotic bone. Each patient received antibiotic prophylaxis: amoxicillin with clavulanic acid (875 mg + 125 mg) every 12 hours. For patients allergic to penicillin, clindamycin (600 mg every 12 hours) was prescribed. Antibiotic therapy began 3 days preoperatively and continued for 14 days postoperatively.

Surgical procedure

In both groups, local anaesthesia without a vasoconstrictor was administered (Mepivacaine 3%, Scandodenst; Septodont). Access was gained using a No. 15c blade attached to a No. 3 handle, and tissues were elevated with a 15-mm semicircular periosteal elevator. In the test group, surgical debridement was performed with an adjunctive Er:YAG laser (LightTouch; Light Instruments), which was used with the following parameters: 400 mJ, 6 W, 15 Hz, 5/8 water cooling, and an 800-micron laser tip ( Table 1 ). Tissue debridement continued until hard, vital, and bleeding bone was exposed, indicating the removal of necrotic tissue. In the control group, patients had conventional surgery alone using 8-mm-diameter rose-shaped rotary drills at a speed not exceeding 40,000 rpm with copious saline irrigation. Tissue removal boundaries were consistent with those used in the laser-treated group. To minimise variability, all surgical procedures were performed by the same FM.

Wound closure and postoperative care

Wounds were closed with 5-0 nonresorbable sutures that were removed 2 weeks postoperatively. Postoperative care included a soft diet, cooling the treatment area with a cooling pack for the first 3 days, and continued use of the prescribed antibiotics. Analgesics were also prescribed.

Postoperative follow-up

Patients were assessed at 1, 2, 4, 12, and 24 weeks postoperatively. During these follow-up visits, the condition of the surrounding mucosa, wound healing, occurrence of complications, and pain were evaluated.

Assessment of harm

Patients were constantly evaluated intraoperatively and postoperatively. Any worsening of clinical findings and assessment would be reported and patients informed. Measures would be taken to either resolve the problem or stop the trial for the patient.

Statistical analysis

The study sample was described in terms of the variables analysed. Qualitative data were presented as numbers (n) and percentages (%), while quantitative data were reported as mean (M) and standard deviation (SD) for normal distributions and as median and lower and upper quartiles for skewed distributions. 43 The range was also reported. The normality of the distribution for quantitative variables was assessed using the Shapiro-Wilk test. 44 The χ 2 or Fisher’s exact test for categorical variables and the t test or Mann-Whitney U test were used for continuous variables, depending on data distribution. 45 , 46 , 47 , 48 A P value less than .05 was considered statistically significant. Logistic regression analyses were performed using the bootstrapping procedure to address nonnormal data distribution. 49 Bias-corrected and accelerated 95% bootstrap confidence intervals (BCaCIs) were calculated. 49 To ensure statistical precision, 5000 bootstrap samples were drawn. 50 , 51 The degree of necrosis severity was assessed using the t test to assess intergroup differences. Cohen’s d effect size coefficient was calculated, 52 with thresholds defined as 0.2, small effect; 0.5, medium effect; and >0.8, strong effect. 53

Sample size calculation

A sample size calculation was performed to determine the number of participants required to detect a significant difference in complication rates between the groups. Based on expected complication rates of 60% in the conventional surgery group and 17% in the combined surgery and adjunctive Er:YAG laser group, 54 , 55 with a power of 80% and a significance level of .05 (2-sided), the estimated sample size was 29 patients per group (total 58). To account for 25% potential dropouts, a total of 72 patients were included in the study.

Outcome variables

The following outcome-dependent variables were evaluated: occurrence of complications, risk of severe necrosis, healing of the mucosa, pain intensity, improvement in the degree of necrosis severity, postoperative pain intensity, and duration of the procedure. The total duration of each surgery was recorded in minutes. Postoperative pain intensity levels were assessed using the visual analog scale preoperatively and at 3 and 6 months postoperatively. Immediate postoperative pain was not assessed due to its potential interference with acute healing processes. Mucosal healing and complications were evaluated by examining mucosal condition, presence of complications, need for further treatment, disease progression, and complete cure rates.

Results

Participants

According to the sample size determination, 72 patients were randomly allocated and randomised into 2 groups. A total of 106 patients were assessed for eligibility. Forty-one patients were excluded from the study. Eighteen patients did not meet the inclusion criteria as they had severe disease (American Society of Anesthesiologists grade III), and 16 patients declined to participate. Six patients did not disclose their reasons for not participating in the study. Sixty-five patients completed the study. Two patients in the control group withdrew from the study, and another patient in the same group elected to withdraw from the study. Three patients from the control group and 1 patient from the Er:YAG group were lost to follow-up. The reasons are mostly related to the exacerbation of cancer or moving out of the country ( Figure 1 ).

Postoperative complications

The logistic regression model assessing the treatment method as a predictor of posttreatment complications was statistically significant (χ 2 (1) = 13.16; P < .001; Nagelkerke R 2 = 0.25; classification accuracy = 72.3%) ( Table 2 ).

The odds of complications among patients treated with conventional surgery were about 1.5 times greater than those without complications in this group, while the odds of complications among patients treated with combined surgery and adjunct Er:YAG laser were about 1:4 (0.21). Patients treated with conventional surgery had 7.55 times higher odds of developing complications compared to those treated with surgery and adjunct Er:YAG laser (odds ratio [OR], 7.55; 95% BCaCI, 2.17-26.54) ( Table 3 ).

Severity of osteonecrosis postoperatively

The logistic regression model was statistically significant (χ 2 (1) = 11.83; P < .001; Nagelkerke R 2 = 0.28; classification accuracy = 83.1%). The odds of developing more severe necrosis among patients treated with conventional surgery were 1:2, whereas the odds of developing grade II/III necrosis 3 months postoperatively among patients treated with the adjunctive Er:YAG laser pulses were approximately 3:10 (0.029). Patients treated with conventional surgery had 18.57 times higher odds of developing grade II/III necrosis at 3 months compared to those in the adjunctive Er:YAG laser group (OR, 18.57; 95% BCaCI, 1.25-359,804,391.29). The relationship between the treatment method and the occurrence of severe necrosis 3 months postoperatively is significant ( Table 4 ).

During the follow-up period between 3 and 6 months, only 1 person (in the conventional surgery group) achieved a reduction in the stage of advancement from III/II to I/0. There were no statistically significant differences between the 3- and 6-month follow-up periods in terms of improvement in the stage of necrosis from stage II/III to I/0 ( Table 5) .

Improvement in necrosis severity depending on the treatment method

A t test analysis showed greater improvement in necrosis severity in patients treated with surgery and adjunct Er:YAG laser (n = 35) (M = 1.94; SD = 0.42) compared to the conventional surgery group (n = 30) (M = 1.50; SD = 0.90). Levene’s test showed a lack of equality of variances ( F = 30.53; P < .001). The difference between groups (0.44 degrees) was statistically significant (t(39.464) = 2.48, P = .009; 95% BCaCI, 0.10-0.77). The obtained effect of the treatment method was moderate (Cohen’s d = 0.65).

Soft tissue mucosal healing

The logistic regression model for mucosal healing was statistically significant (χ 2 (1) = 24.74; P < .001; Nagelkerke R 2 = 0.43; classification accuracy = 80%). The odds ratio of nonhealing of the mucosa for patients treated with conventional surgery, relative to those treated with surgery and adjunct Er:YAG laser, estimated using the bootstrapping procedure, was 44.0 (95% BCaCI, 1.97-24.70). The odds of nonhealing of the mucosa among patients treated with conventional surgery were approximately 44 times higher than those treated with surgery and an adjunct laser ( Table 6 ).

The odds of mucosal nonhealing among patients treated with conventional surgery were 2.75 times higher than the odds of mucosal healing, whereas the odds of mucosal healing among patients treated with surgery and adjunct Er:YAG laser were 6 times higher than for mucosal nonhealing. The odds ratio of nonhealing of the mucosa in patients treated with conventional surgery compared to those treated with surgery and adjunct Er:YAG laser estimated using the bootstrapping procedure was 18.33 (OR, 18.33; 95% BCaCI, 4.69-66.00). The relationship between the method of treatment and nonhealing of the mucosa was significant, and the odds of nonhealing of the mucosa among patients treated with conventional surgery were approximately 18.33 times higher than among those treated with surgery and an adjunct laser.

Follow-up mucosal healing stability

There were no changes in mucosal healing status between the 3-month and 6-month follow-up periods. The condition remained stable across both groups during this time ( Table 7 ).

Postoperative pain intensity

Regardless of whether patients with MRONJ were treated with surgery alone or combined with adjunct Er:YAG laser therapy, there was a significant difference between preoperative (6.80 ± 2.30) and postoperative pain levels at 3 months (2.54 ± 2.44, P < .001) and at 6 months (1.77 ± 2.23, P < .001). Pain was reduced significantly at 6 months compared to pain levels at 3 months and to preoperative pain. The preoperative pain levels for patients with MRONJ treated by surgery alone (6.47 ± 2.53) were not significant compared to those in patients with MRONJ treated by surgery combined with adjunct Er:YAG laser therapy (7.09 ± 2.06, P > .05). However, at 3 and 6 months postoperatively, the pain levels in patients with MRONJ treated by surgery alone (3.93 ± 2.68, 3.13 ± 2.52) were significantly higher than in patients with MRONJ treated by surgery combined with adjunct Er:YAG laser therapy (1.34 ± 1.39, 0.60 ± 0.95; P < .05), respectively ( Table 8 ).

Duration of the procedure

There was a significant difference in the average length of the procedure in patients with MRONJ who had traditional surgery alone (57.90 ± 7.84 minutes; 95% CI, –15.55 to –8.71) versus patients who had surgery combined with adjunct Er:YAG laser therapy (70.03 ± 5.95 minutes; 95% CI, –15.64 to –8.62; P < .001). Patients with MRONJ who underwent surgery combined with adjunct Er:YAG laser therapy had an average increase of 12.13 minutes compared to patients with MRONJ treated with surgery alone ( Table 9 ).

None of the patients were harmed during the study. There were no reasons to stop treatment for any of the patients.

Discussion

MRONJ is a complex and multifactorial disease, influenced by a patient’s age, previous dental or surgical interventions, level of vitamin D, and systemic conditions, most notably advanced-stage cancers, such as breast cancer, prostate cancer, or multiple myeloma. 11 , 56 , 57 , 58 , 59 Importantly, the route of bisphosphonate administration significantly affects the risk of MRONJ; intravenous BSs are associated with a substantially higher incidence compared to oral routes. 60 , 61 , 62 In addition to oncologic conditions, osteoporosis—especially prevalent in postmenopausal women—is another common underlying disease associated with MRONJ. 63 , 64 Current clinical guidelines, primarily from the AAOMS, have evolved through successive updates in 2007, 2009, 2014, and 2022. 65 While pharmacologic management remains the standard of care in stages I and II, surgical interventions have traditionally been reserved for stage III cases. However, emerging evidence, including findings from our study, supports the efficacy of surgical approaches, especially laser-assisted techniques—even in earlier stages (I and II). 66 , 67 , 68 Our results demonstrated that the use of the Er:YAG laser as an adjunct to surgical treatment in stage II MRONJ was associated with a significantly higher rate of complete healing compared to conventional rotary instruments.

The positive outcomes observed with the Er:YAG laser may be attributed to several factors, such as enhanced mucosal and bone healing 69 , 70 ; bone surface irregularity created by the Er:YAG laser, which promotes blood adhesion during early healing phases; and absence of a smear layer on bone tubules, improving cellular adhesion and minimising microbial retention. 71 , 72 , 73 , 74 The advantage of the Er:YAG laser is also precise tissue removal without melting or carbonisation, unlike CO 2 lasers. 75 , 76 Improved decontamination is especially important in compromised vascular environments like those seen in MRONJ, 55 and bactericidal and biostimulatory effects, in addition to reduced mechanical vibration, contribute to increased patient comfort and wound stability. 25 , 76 , 77 , 78

The results align with the existing literature, 79 , 80 reinforcing the clinical advantage of Er:YAG laser use over traditional drilling techniques with cooling. The 6-month follow-up period in our study allowed for a comprehensive assessment of healing dynamics and the late emergence of complications. Additionally, soft tissue healing was significantly improved in the laser group, with fewer mucosal dehiscences observed. The pain scores, particularly during the first 3 months postoperatively, were markedly lower in the Er:YAG group, which may correlate with faster soft tissue regeneration and reduced intraoperative trauma.

The sex distribution in our study mirrors findings by Momesso et al, 32 with women comprising most cases, likely due to the higher prevalence of osteoporosis and bisphosphonate therapy in this population (ratio of 2:1).

MRONJ remains a condition without a universally accepted treatment protocol. 81 , 82 , 83 Therefore, depending on the stage, clinicians propose specific solutions that are constantly subject to further research and evaluation. 84 Apart from conservative treatment methods (eg, chlorhexidine rinses, systemic antibiotics), 85 especially in early stages, surgical intervention is increasingly recognised as the more effective approach. Surgical management has achieved significantly better outcomes than conservative measures alone. 12

The study had several limitations. Although randomisation was implemented, the convenience sampling technique could potentially result in selection bias and limited external generalisability. Even though the procedures were performed by a single surgeon to ensure consistency, and although the surgeon was blinded to the allocation of treatment but not the treatment itself, this could have resulted in a performance bias. In addition, the mucosal healing and pain scores were subjective, as they were based on clinical judgement and self-reported visual analog scale scales. Finally, the follow-up period of 6 months, while adequate for assessing short-term healing, does not assess the durability of outcomes. Future research studies could incorporate measures of quality-of-life outcomes and longer follow-up periods.

The findings of this study add to the growing body of evidence supporting early and precise laser-assisted surgery, particularly using the Er:YAG laser, as a safe, effective, and patient-friendly treatment for MRONJ in its moderate to advanced stages.

Conclusions

The present study highlights the clinical advantage of Er:YAG laser-assisted surgery in the treatment of stage II and III MRONJ. While patients treated with conventional surgery showed an approximately 50% probability of symptom resolution, those treated with adjunctive Er:YAG laser demonstrated over 90% success in eliminating severe MRONJ symptoms.

Moreover, the data confirm that MRONJ remains a potentially recurrent disease, emphasising the need for effective and minimally invasive therapeutic strategies. Considering both the statistical outcomes and the existing body of literature, the use of the Er:YAG laser as an adjunct in the surgical management of MRONJ appears highly justified, particularly in moderate to advanced stages of the disease.

The benefits of laser-assisted treatment include improved mucosal healing, fewer postoperative complications, and significantly reduced pain, therefore supporting the integration of this method into routine clinical practice. One of the most notable advantages is enhanced soft tissue healing, which substantially contributes to overall treatment success and patient comfort.

Using the Er:YAG laser combined with surgery resulted in a longer procedure time compared to conventional surgery, particularly in extensive cases involving multiple teeth. On average, laser procedures took about 20% more time, largely due to the smaller diameter of the laser tip and its slower rate of necrotic tissue removal. However, this trade-off is outweighed by the superior clinical outcomes observed.

In conclusion, the Er:YAG laser represents a safe, effective, and patient-centred adjunct to traditional surgical approaches for MRONJ, with distinct advantages that justify its broader adoption in clinical settings.

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Contributor Information

Hani Abd-Ul-Salam, Email: hani.salam@mcgill.ca, hani.abdulsalam@auib.edu.iq, hani.salam@utoronto.ca.

Kinga Grzech-Leśniak, Email: kinga.grzech-lesniak@umw.edu.pl.

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