Evaluating the effectiveness of advanced platelet-rich fibrin, photobiomodulation, pentoxifylline, and Alveogyl in the treatment of alveolar osteitis: a randomized controlled clinical trial

Alveolar osteitis is characterized as minor, superficial osteomyelitis of the alveolar bone and influenced by a range of local and systemic factors [26]. The aim of this study was to explore the potential of the inclusion of PTX as a treatment option and compare its effectiveness with that of other established methods. According to the findings of this study, all the treatment groups exhibited comparable outcomes in terms of pain management. However, A-PRF and PBM were identified as the most effective methods for promoting soft tissue healing. The null hypothesis regarding pain was confirmed, but it was not validated in terms of soft tissue healing.

All the methods used in this study were successful in alleviating pain in patients with alveolar osteitis. Previous studies have shown Alveogyl, PBM, and A-PRF to be effective in terms of analgesic properties in cases of alveolar osteitis, which is consistent with the pain-relieving effectiveness results of this study. Although PTX is novel in this context and not primarily recognized for its analgesic effects, it effectively manages pain in patients with alveolar osteitis, possibly owing to its role in accelerating soft tissue healing [26]. Previous findings suggest that PTX shortens the inflammatory phase in the early stages of wound healing, leading to faster development of healing phases, although its effect may slow down in the later stages of wound healing [26]. In studies, PTX has been reported to be safe and associated with minimal side effects even with long-term use [27, 28]; consequently, it was administered for a limited duration in the present study to mitigate potential side effects associated with prolonged use. Patients tolerated PTX well throughout the treatment period. In this study, while PTX did not provide significant advantages, it may be considered a supportive medication in future clinical trials alongside existing treatment protocols. In general, it reached similar clinical efficacy levels as Alveogyl at the end of the 2nd week in the LHI evaluation and PBM at the end of the 7th day in the granulation tissue evaluation. Therefore, the difference that will occur in combined applications with other methods is likely to be at a level that will be reflected in statistics.

In studies on the treatment of alveolar osteitis, lower pain scores were observed with the application of PRF than with Alveogyl and zinc oxide eugenol (ZnOE) [29, 30]. PRF has also been found to be superior to Alveogyl in soft tissue healing [30]. In the only study in the literature conducted with A-PRF for treating alveolar osteitis, A-PRF was reported to significantly reduce pain and promote healing in both soft and bone tissues [16]. PRF products obtained at lower centrifugation speeds, such as A-PRF, arguably release higher levels of growth factors, support type-I collagen production, and thereby make significant contributions to soft tissue healing [31]. In cases where bone tissue is exposed, such as alveolar osteitis, the application of A-PRF may accelerate soft tissue healing and, through support for epithelialization and immunomodulation [32], indirectly lead to reduced pain scores. According to the results of the present study, A-PRF and PBM were the two groups that presented the greatest decreases in pain scores during the follow-up period. Additionally, the A-PRF and Alveogyl groups demonstrated better results in terms of granulation tissue formation. This study’s findings are consistent with the literature. In studies comparing photobiomodulation with control groups, PBM has been shown to exhibit superior analgesic effects and promote better soft tissue healing [11, 12, 22]. In the study by Al Harthi et al., which evaluated the effectiveness of Alveogyl, Alveogyl combined with PBM, and PBM alone for pain relief for alveolar osteitis, the combination of Alveogyl and PBM was found to be the most effective approach [33]. During the first three days, the pain levels in the Alveogyl + PBM group were greater than those in the Alveogyl alone group. However, at days three and four, similar results were observed between the PBM and Alveogyl + PBM groups. No significant differences in pain relief were found between the Alveogyl and PBM groups. Eshghpour et al. found that Alveogyl demonstrated greater efficacy than PBM in the initial two days following treatment, while also noting that PBM yielded acceptable VAS scores in the management of alveolar osteitis [34]. Similarly, in this study, the mean VAS scores on the second day were comparable between the PBM and Alveogyl groups. In the present study, the PBM group demonstrated superior soft tissue healing based on LHI data compared with the other groups but showed similar analgesic efficacy. Importantly, this study involved interventions rather than allowing the healing process to occur naturally in each group. Therefore, we believe that our findings contribute positively to the literature on this topic.

Sex was a significant factor influencing pain outcomes in the present study. The mean VAS score was greater among female patients than male patients, both preoperatively and on the 4th postoperative day. This result aligns with the literature indicating a higher incidence of alveolar osteitis in females [35]. Similarly, in this study, a greater proportion of female patients were observed, with females experiencing more severe pain from alveolar osteitis than males did.

Alveolar osteitis is commonly reported to increase with age, particularly affecting individuals in their third and fourth decades of life. However, the present study yielded a contrary finding in which alveolar osteitis cases were predominantly observed in individuals aged 18–27 years (33.8%). This discrepancy may be attributed to the higher prevalence of third molar extractions in young adults, as alveolar osteitis is most frequently associated with third molars [36]. In the present study, the incidence of alveolar ostieitis was similar between the 1st + 2nd mandibular molars and 3rd molars.

Interestingly, while the A-PRF group had a mean age over 40 years, the PTX group included younger patients. This variation in age distribution may have inadvertently influenced the present study’s results. Future studies could benefit from the use of randomization methods to balance age distributions across groups, potentially mitigating such influences.

The methods investigated in the present study—Alveogyl, PBM, and A-PRF—have demonstrated effectiveness in treating alveolar osteitis compared with control groups in previous studies [12, 16, 37]. In this study, we compared these effective methods against each other, and the alveogil group served as a positive control group due to its inclusion in accepted treatment protocols [38]. This factor likely contributed to the absence of significant differences observed between the groups during certain periods. Patients in the Alveogyl group initially presented with higher preoperative soft tissue values than those in the other groups did, suggesting potentially better baseline healing conditions. However, PBM and A-PRF exhibited accelerated healing trajectories in terms of improvement over the follow-up period.

In the present study, patients with alveolar osteitis involving the mandibular first, second, or third molars were included. This decision was influenced by several factors, including the need for standardization, the physiological advantages of the mandible over the maxilla, gravitational benefits, and the relatively smaller wound area of the anterior and premolar teeth. Although this approach could be perceived as a limitation, efforts were undertaken to minimize local and anatomical variations, thereby enabling an objective evaluation of the effectiveness of the treatment methods. A limitation of this study is the inability to achieve an equal distribution of age groups. Given that individuals aged 40 and older may experience disadvantages in wound healing, the distribution was adjusted accordingly [39, 40]. Consequently, the mean ages across the groups were not very similar. A distribution over more blocks could have been achieved by narrowing the age ranges further. Although excluding individuals over 40 years of age might have mitigated this concern, we chose to include them to ensure better population representation. Despite the higher average age in this cohort, A-PRF demonstrated notable efficacy. While the older average age in the PTX group may have provided a potential advantage for wound healing, the clinical outcomes were not superior to those observed in the other groups.

Given that alveolar osteitis is painful, it would have been unethical to withhold analgesics. Therefore, all patients received analgesic treatment, which likely impacted the pain data. To mitigate this effect, we standardized treatment by administering the same analgesic with mild anti-inflammatory properties to all patients.

The symptomatic period for alveolar osteitis typically lasts 7 to 10 days [38, 41]. Most studies follow up for approximately two weeks, so we also assessed soft tissue healing over this duration [13]. Pain typically diminishes during the initial week; therefore, assessments concentrated on this early period. While extended follow-up could have been implemented, it was deemed preferable to forgo this option to minimize the potential for increased clinical visits and the associated risk of data loss.

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