For improving the MRONJ healing process, we need to reduce the medications' inhibitory effects by accelerating bone and soft tissue regeneration with adjuvant therapies. There are various reports of adjuvant therapies; however, these treatments' efficacy in comparison or combination with one another has yet to be established [8, . The success rate of such treatments depends on their required frequency, costs, complexity, and patient collaboration. Hence, we selected two available and cost-effective adjuvant therapies (PBM and PRF therapy) to investigate.
The necrotic bone's presence causes constant soft tissue irritation and thus interferes with proper healing . Exposed bone and epithelialization absence result in persistent and recurrent infections postponing the healing . Therefore, necrotic bone elimination is essential. According to Hayashida et al. , the first treatment choice should be surgical therapy, and prolonged conservative therapy may decrease the patient's quality of life and exacerbate the lesion. Accordingly, we applied surgical resection to all experimental groups as the primary treatment.
Based on our findings, surgical treatment (S group) resulted in lower mean wound dimensions and higher bone density than the C group. However, there were no substantial improvements in other clinical and histological parameters. Most specimens from the S group had severe inflammation, moderate vascularization, and unsatisfactory epithelial integrity. Consequently, surgical resection is required to provide the underlying healthy margins for tissue regeneration, but it cannot enhance the regeneration alone.
Adjuvant PBM therapy resulted in similar outcomes as the surgery. Although, PBM therapy resulted in lower mean empty lacunae than the C group. The inflammation and vascularization of most P group specimens were also reduced, which could be justified by the granulation tissue maturation. Since there was no obvious bone formation progression, we supposed that the fibrotic tissue formation replaced the granulation tissue.
Similar to our study, Vescovi et al.  suggested that PBM applications stimulate angiogenesis and soft tissue healing. Based on the systematic review by de Souza Tolentino et al. , from 246 cases who underwent laser therapy, 64.2% showed improved symptoms, and 39.8% were healed completely. Many studies have confirmed the positive PBM effects on tissue regeneration, including promoting cell proliferation, calcium deposition, and angiogenesis . In this study, we could not detect PBM stimulation effects on bone regeneration which might be explained by the suppression effect of zoledronate on bone remodeling . Likewise, Ervolino et al.  observed that PBM therapy could not alter the bone remodeling in extraction sites of rats treated by zoledronate.
Notably, PBM outcomes are highly dependent on various factors, such as laser wavelength, laser settings, and sessions' frequency and duration. The pre-treatment MRONJ stage also affects the PBM therapy's success rate.
The present study also investigated the PRF therapy effect on MRONJ healing. Based on our findings, in the cases treated with PRF (A and L groups), the mean wound and bone exposure area dimensions were considerably lower than the C group. All extraoral and intraoral fistulas were healed except for one case. Most cases showed satisfactory and highly satisfactory mucosal healing. Enhanced bone remodeling was detected in these groups, which was expected due to inflammation reduction, vascularization reduction, and granulation tissue maturation. The epithelial integrity was also better than the previous groups.
PRFs affect MRONJ remission by mechanical and inflammatory protections and enduring bio-activator properties . Their fibrin architecture provides a scaffold that stores cells such as platelets and prevents the direct toxicity of bone-released bisphosphonates on the soft tissue by acting as a barrier between bone and oral mucosa [29, . Trapped platelets in these fibrins are responsible for releasing growth factors, upregulating osteoprotegerin and alkaline phosphatase, and osteoblasts' proliferation [31, .
Unlike PBM therapy, PRFs' regenerative properties persist for a significant time throughout the healing process (usually 7 to 28 days) and do not need repetition . This might explain the better outcomes observed in a one-month follow-up after PRF treatment rather than PBM.
In many case reports and a few clinical trials on MRONJ, the PRFs' application has shown promising results [29, [33, . Based on Kim et al.'s study , 26 out of 34 patients showed complete MRONJ resolution after L-PRF treatment. Giudice et al.  investigated the PRF's efficacy after surgery compared to surgery alone at three different time points. Their results exhibited significant differences in mucosal integrity, infection absence, and pain resolution between treatment groups in favor of PRF at the one-month follow-up.
PRFs' preparation is an economical and straightforward process with no technical difficulties. They are chemical-free products from patients' blood that can be easily handled. Considering the mentioned advantages, PRF therapy is an appropriate adjuvant treatment for MRONJ.
We also investigated the efficacy of simultaneous PRF and PBM therapies (A+P and L+P groups). These were the only groups that showed a higher statistically significant number of osteocytes (P ˂ 0.05). Moreover, we observed substantially higher mean bone density and fewer empty lacunae than C, S, and P groups. These groups showed complete healing of fistulas and 6 out of 7 cases of highly satisfactory mucosal healing. They were the only groups showing slight inflammation and highly satisfactory epithelial integrity.
These results indicate the synergic effect of PBM and PRF co-application. The PBM bio-stimulatory effects might activate PRFs' platelets, leading to enhanced growth factors releasing and tissue remodeling.
Merigo et al.  treated 21 MRONJ patients using platelet-rich plasma (PRP) and 808 nm laser after removing necrotic tissues by piezosurgery and Er:YAG laser. 92.85% of patients reached complete healing at six-months follow-up. Hence, they suggested consecutive different high-technology strategies during the MRONJ treatment. Using different methods to eliminate the necrotic tissues and PRP instead of PRF hinders comparing the results between our study and theirs. However, they also supported the application of more than one adjuvant therapy.
Finally, it is worth mentioning that despite applying two different protocols to prepare PRFs (A-PRF and L-PRF), we detected no significant differences between them (P ˃ 0.05).
Within the treatment selections investigated in this study, we concluded that the combination of PBM and PRF placement might be the most practical choice of MRONJ treatment. These adjuvant therapies improved clinical, histological, and radiological parameters examined in this study. PRF therapy alone revealed better outcomes than PBM alone, and we observed no substantial differences between A-PRF and L-PRF.