Background and Clinical Significance: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive therapies such as Zolendronic acid, used for bone metastases. Its management remains challenging, with outcomes often unpredictable. Platelet-rich fibrin (PRF), rich in growth factors, has been proposed as a potential adjunct to surgical treatment, aiming to promote tissue regeneration and improve patient outcomes. Case Presentation: We reported three clinical cases of MRONJ in patients previously treated with Zolendronic acid. All patients underwent surgical sequestrectomy combined with A-PRF application. Disease stages ranged from early to advanced (stages I–III). The success of treatment was evaluated based on how well the tissue healed, the extent of bone recovery, the amount of pain relief, and improvements in the patient’s quality of life. The patient with early-stage MRONJ achieved complete healing. On the other hand, the patients with stage II and III disease showed only partial clinical improvement. Nevertheless, all cases demonstrated significant subjective reduction in pain and enhanced overall quality of life following PRF therapy. Conclusions: Early-stage intervention offers the best prognosis for MRONJ. While A-PRF may improve postoperative comfort and quality of life, its curative effect appears limited in advanced disease. This highlights the need for further randomized clinical trials to demonstrate the role of A-PRF in the treatment of MRONJ.

Background and Objectives: Platelet-rich fibrin (PRF) has been widely investigated as a biological material to enhance healing after tooth extraction; however, its clinical effectiveness remains uncertain. This systematic review evaluates the available evidence on its effectiveness in post-extraction socket management. Materials and Methods: A literature search was conducted across eight electronic databases for English-language studies published between 2015 and 2025. Only randomized controlled trials, including parallel-group randomized trials and randomized split-mouth trials, involving PRF with a control group were considered. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB 1). Due to substantial clinical heterogeneity in PRF preparation protocols, outcome measures, and follow-up periods, a narrative synthesis was performed instead of a meta-analysis. Results: A total of 174 records were identified, of which 9 studies met the inclusion criteria. The methodological quality of the studies included was evaluated to assess the risk of bias, in accordance with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. Overall, 394 patients underwent 817 tooth extractions: 414 sockets were treated with different types of PRF, 251 were left to heal after suturing, and 143 were filled with a hemostatic sponge prior to suturing. Conclusions: PRF demonstrated superior outcomes in soft tissue healing and radiographic new bone density, although no statistically significant differences were observed in other parameters. Therefore, the available evidence does not allow us to draw definitive conclusions regarding the clinical effectiveness of PRF for socket filling after tooth extraction. The literature indicates that it may promote soft and hard tissue healing and reduce pain, swelling, and the risk of alveolar osteitis; however, evidence regarding its therapeutic effect on alveolar socket healing remains contradictory.