Is injectable platelet-rich fibrin really effective in alveolar osteitis? a randomised controlled clinical trial

Abstract

Background

Alveolar osteitis(AO) is an inflammatory and painful condition that occurs due to distruption of the fibrin matrix within the extraction socket following tooth extraction. This study investigates the effectiveness of I-PRF in reducing pain in AO patients compared to conventional treatment.

Materials and methods

This prospective randomized controlled study included patients experiencing localized AO treated at the Oral, Dental, and Maxillofacial Surgery clinic between October 2024 and February 2025. Sixty patients diagnosed with AO were randomly assigned to two groups. The control group (Group 1) received standard treatment consisting of socket curettage followed by saline irrigation. The I-PRF group (Group 2) received I-PRF application after curettage and irrigation. Pain levels were assessed using the Visual Analog Scale (VAS) on postoperative days 3 and 7.

Results

The study included 60 patients (28 males, 32 females) aged between 19 and 68 (mean 37.40 ± 12.81). There was no significant difference in preoperative VAS scores between the groups (p>0.05). On postoperative day 7, the I-PRF group showed a significant reduction in VAS scores compared to the control group (1.27 vs. 2.27, p<0.05). Our results show that I-PRF significantly reduces pain levels, offering a promising alternative to traditional therapies.

Conclusion

I-PRF significantly reduces pain in AO patients compared to conventional treatment. These findings suggest that I-PRF could be a valuable addition to clinical practice, but further studies are needed to confirm its long-term effectiveness.

Trial registration

Clinical Trials.gov Registration ID NCT06761001. Registered 30/12/ 2024- Retrospectively registered.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-025-06257-y.

Background

Alveolar osteitis (AO) is a painful and inflammatory complication that arises after tooth extraction due to the disintegration of the fibrin matrix in the socket. Clinically, AO typically manifests within 1–3 days post-extraction with intense, throbbing pain that may radiate to the ear or temporal region, and is often accompanied by halitosis [1–4]. Although the etiology of AO is not yet clear, fibrinolysis that develops after bacteria invade the extraction socket is defined as the most common cause [5, 6]. There are many predisposing factors for the development of AO, such as the patient's existing systemic diseases, smoking, oral contraceptive and other drug use, the technique used by the surgeon, and the patient's oral hygiene preoperative and postoperative [7, 8]. Techniques such as chlorhexidine gargle, antibiotics, topical gels, various medical dressings, and application of topical anesthetics are reported to be effective in the treatment of AO, but there is no reported standard treatment for AO [9, 10].

Today, autologous blood products such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and consantrated-growth factor (CGF) are used in many areas of dentistry and medicine and have been found to be beneficial in tissue healing and reducing inflammatory responses [11]. I-PRF, unlike other types of PRF, is in an injectable form and contains more leukocytes, growth factors and platelets in the liquid matrix compared to other types due to the lower centrifugation speed. Among the advantages of I-PRF is that it has a more stable and sustainable release compared to PRP [12]. I-PRF is used in various maxillofacial procedures such as reducing complications after tooth extraction, treatment of TMJ disorders, sinus lift operations and cyst operations [13, 14].

The purpose of this study was to evaluate the clinical efficacy of I-PRF in alleviating pain in patients diagnosed with AO, compared to conventional treatment. To the best of our knowledge, no prior studies have investigated the use of I-PRF specifically in AO management. This research therefore aims to fill a gap in the literature and assess whether I-PRF could be a valuable addition to clinical protocols for AO treatment.

Material and methods

The study was approved by Eskişehir Osmangazi University Clinical Research Ethics Committee with the decision number 2024–07(01) (Approval No:E-80558721-050.04-240189062). The study was registered at the Clinical Trials Registry (NCT 06761001). The study was carried out following the principles stated in the Declaration of Helsinki and the recommendations given in the Unified Standards of Research Reporting guide. Comprehensive information regarding the instruments to be utilized, the study’s design, duration and objectives was provided to all participants. Patients were selected at random using a computer-based random number generator to ensure unbiased allocation.

Trial design

This study is a single-center, prospective, parallel-group, randomized controlled clinical trial with a 1:1 allocation ratio. It was conducted on patients who underwent tooth extraction for various reasons between October 2024 and February 2025 and were directly referred or referred to Eskişehir Osmangazi University, Faculty of Dentistry, Oral and Maxillofacial Surgery Clinic for AO treatment. The study’s objective was explained to the patients and informed consent was signed before the conduction of the study.

Participants

Inclusion Criteria: Patients aged ≥18 years, diagnosed with AO based on clinical findings (severe pain, clot loss, foul odor within 48–72 h post-extraction), attending follow-up visits.

Exclusion Criteria: Smoking, pregnancy or breastfeeding, systemic diseases affecting healing (e.g., diabetes, bleeding disorders), use of bisphosphonates or history of radiotherapy to the jaw.

Informed consent was obtained from those who consented to take part in the study. Patients were informed that there was no blinding in our study and were informed about the procedure for obtaining blood samples to obtain I-PRF.

Interventions

A total of 60 participants were included in our study, 30 in each group. Two groups were created, consisting of patients who applied with complaints such as pain in the extraction socket after tooth extraction, bad breath and were diagnosed with AO, along with the demographic data of the patients. The first group, the control group, the sample included 30 patients. The patients in this group were applied the protocol of curetting the extraction socket and then irrigating it with sterile physiological serum, which is routinely applied in our clinic for AO treatment. The second group, the I-PRF group, included a total of 30 patients. The I-PRF protocol was explained to the patients in this group and the necessary consents were obtained. I-PRF was applied after curettage and physiological serum application to the AO extraction sockets (Fig. 1). All procedures were performed by the same clinician, ensuring consistency across the study. This has been clarified in the revised manuscript.

Fig. 1.

The flow chart of the study

I-PRF protocol

Blood was collected using a 9 mL vacuum-sealed tube. Blood was filled into vacuum tubes without anticoagulant with a suitable syringe from the antecubital vein. The tube filled with venous blood was centrifuged in a centrifuge device at 700 rpm for 3 min. Upon completion of the centrifugation process, layer of I-PRF formed at the top of the tube was extracted with a 21-gauge syringe and injected into the socket (Fig. 2).

Fig. 2.

Application of I-PRF with a single-use 21-gauge syringe after debridement and saline irrigation of the infected socket

Outcomes

The primary outcome was pain reduction, assessed by VAS scores preoperatively and on postoperative days 3 and 7. In this study, patients with AO were asked to select the numerical value reflecting their pain level between 0 and 10 (0; least, 10; most) with the VAS method before and after treatment. For the patients who came for control, age, gender, jaw area of the extraction socket where AO was seen and standard on the preoperative, postoperative 3rd and 7th days VAS score were evaluated.

Sample size collection

The sample size of the study was determined using G*Power software (Version 3.1.3; Franz Faul Universitat, Kiel, Germany). To achieve 80% power, 0.05 margin of error, and d = 0.8 effect size, a minimum of 26 participants per group were required.

Randomization

Randomization was performed by selecting patients randomly from those who presented for treatment.

Blinding

Due to the nature of the intervention, blinding was not feasible for participants or clinicians.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics Version 20 (IBM Corp., Armonk, NY). The Shapiro–Wilk test was applied to assess whether the data followed a normal distribution. For comparisons between groups, the Mann–Whitney U test was utilized. A p-value of less than 0.05 was regarded as indicating statistical significance.

Results

The study involved a total of 60 patients, 30 (50%) in the control group and 30 (50%) in the I-PRF group. The patients’ ages ranged from 19 and 68 (mean 37.40±12.81). 28 (46.7%) of the patients were male and 32 (53.3%) were female.

AO was seen in the maxilla in 31 (51.7%) and in the mandible in 29 (48.3%) of the 60 patients. AO was seen in the maxilla in 15 (46.9%) of the female and in the mandible in 17 (53.1%), and in the maxilla in 16 (57.1%) of the male and in the mandible in 12 (42.9%).

The distribution of participants in the control and I-PRF group based on gender and jaw localization is shown in Table 1. The control group comprised 16 female and 14 male participants, while the I-PRF group also comprised 16 female and 14 male patients. In the control group, 14 AO cases were seen in the maxilla and 16 in the mandible; in the I-PRF group, 17 AO cases were seen in the maxilla and 13 in the mandible.

Table 1.

Demographic distribution of participants by gender and AO localization in control and I-PRF Groups

Variables	Control Group (n = 30)	I-PRF Group (n = 30)
Gender
Male	14 (46.7%)	14 (46.7%)
Female	16 (53.3%)	16 (53.3%)
Jaw Localization
Maxila	14 (46.7%)	17 (56.7%)
Mandible	16 (53.3%)	13 (43.3%)
Total	30 (100%)	30 (100%)

Count data are expressed as numbers (%)

 Abbreviation I-PRF injectable platelet-rich fibrin

The mean VAS scores before the operation and on the 3rd and 7th days after the operation are shown in Fig. 3. When the preoperative, 3rd and 7th day VAS values ​​were compared between the groups; no statistically meaningful difference was observed between preoperative and 3rd day. On postoperative day 3, the mean VAS score was 4.40±2.27 in the control group and 3.67±1.27 in the I-PRF group. Although the I-PRF group showed a slightly lower average pain score, the difference was not statistically significant (p>0.05). On the 7th day, VAS scores were significantly lower in the I-PRF group (p<0.05). No statistically siginificant difference was observed between the groups when compared by age. (p>0.05) (Table 2) No complications or adverse effects related to I-PRF application were observed during the follow-up period.

Fig. 3.

Comparison of VAS Scores Over Time Between the Control and İ-PRF Groups

Table 2.

Comparison of age and Visual Analog Scale (VAS) pain scores between control and I-PRF groups at baseline, postoperative day 3, and day 7

Groups	Age (year)	VAS Scores
		Before Treatment	Day 3	Day 7
Control group (n = 30)	38,37 ± 12,91	6,87	4,40	2,27
I-PRF group (n = 30)	36,43 ± 12,85	6,43	3,67	1,27
p value	0,46	0,34	0,07	0,01*

Measurement data are expressed as means ± standard deviations

Abbreviations I- PRF injectable platelet-rich fibrin, VAS visual analog scale, Mann Whitney U test

*Statistical significance p < 0.05

Discussion

Pain is regarded as the most prevalent and distressing symptom of OA and requires effective treatment [15]. Therefore, it is important that the patient's treatment be carried out quickly to reduce the agitation and pain caused by AO [3] However, no standard treatment protocol has been established to treat pain associated with AO, and choosing the best treatment option remains a challenge for clinicians [16].

Shafaee et al. [17] assessed and compared the efficacy of photobiomodulation (PBT) with other therapeutic approaches for AO. They reported that PBT generally has a greater ability to alleviate pain levels in patients with AO in comparison to alveogyl. Therefore, they recommended that PBT could be an effective method for treating and managing the symptoms of dry socket. Rosa et al. [18] evaluated materials that may help in pain management, reducing inflammation, and enhancing wound healing in AO in a meta-analysis and reported that laser therapy could serve as a viable alternative to conventional treatments for dry socket. They reported that this minimally invasive procedure may offer the potential to relieve pain and promote healing with fewer side effects. The fact that PBT and laser are not available and cannot be applied in every clinic constitutes the limitations of the study and has led to the search for new studies. Dereci et al. [3] compared the efficacy of Alveogyl, 0.8% hyaluronic acid (HA) and 0.2% chlorhexidine digluconate (CHX) gel in alleviating pain and enhancing the clinical manifestations AO. Initially, all patients treated with curettage followed by irigation with physiological saline, after which they were categorized into four groups. Group 1 was served as the control group, with no additional biomaterials applied following curettage and irrigation with saline. Alveogyl, HA and CHX were applied separately to the other groups. They reported that no notable difference was observed between the control group and Alveogyl, HA or CHX in reducing pain in AO. They stated that prospective studies should be conducted. In our study, we evaluated the effectiveness of I-PRF by applying a prospective study and compared it with the control group. While the study applied multiple groups and no difference was found between the groups, our study showed the effectiveness of I-PRF by significantly reducing pain in AO patients..

Wang et al. [19] compared the effectiveness of PRF and iodoform gauze for localized AO treatment. In his prospective study, 60 patients were enrolled, with an equal and random allocation into the control and PRF groups. He reported that one week following the treatment of AO, the PRF group demonstrated a superior healing rate compared to the control group (93.3% vs. 60.0%). He also reported that the PRF group had notably lower VAS pain scores on the 3rd day (1.10 vs. 4.17) and 7th day (0.30 vs. 1.73, P < 0.05) after surgery compared to the control group. He suggested that PRF application gave successful results and could be used. According to the results of the meta-analysis, it was reported that PRF significantly reduced pain, accelerated wound healing and could reduce AO formation, which provided a significant advantage over standard treatment. Furthermore, the biocompatibility and ease of preparation of PRF has been reported to make it a cost-effective and patient-friendly alternative that could potentially decrease the reliance on analgesics and antibiotics [8]. Sharma et al. [20] assessed the impact of platelet-rich fibrin (PRF) on pain relief and healing of the extraction socket in cases AO following the extraction of maxillary and mandibular molars. The study involved 100 adult participants, aged between 18 and 40, who had not previously undergone treatment for AO. They reported that there was a notable reduction in AO-related pain in the extraction socket on the 3rd and 7th days after PRF placement. Despande et al. [21] also conducted a study suggesting that platelet-rich plasma (PRP), an autologous platelet concentrate, accelerates wound healing and reduces the incidence of AO. This randomized controlled trial included 100 young adult patients aged 18–35 years who underwent mandibular third molar extraction. Patients were randomly divided the into two groups: the PRP group (n = 50) and the control group (n = 50). The incidence of localized AO was significantly lower in the PRP group (6%) compared to the control group (20%) (P < 0.05). Patients in the PRP group reported mean pain scores of 2.5 and 1.2 on the VAS on days 3 and 7, respectively. These scores were 4.0 and 2.8, respectively. They reported that the incidence of AO after mandibular mandibular third molar extraction was significantly reduced with the application of PRP. As seen in the studies, autologous blood products are effective in reducing pain. However, there is no AO treatment with I-PRF in the literature. It is thought that our study will make significant contributions to the treatment of AO with I-PRF, which is lacking in the literature.

Akpiar et al. [13] designed a prospective study consisting of 43 patients to evaluate the effectiveness of I-PRF. Split Mouth applied I-PRF to the sockets after tooth extraction and compared it with the control group. The study findings indicated that I-PRF demonstrated a limited effect in controlling post-extraction pain. Uranbey et al. [22] also evaluated the effectiveness of IPR applied to extraction sockets and reported that the I-PRF group showed positive effects on pain. Studies in the literature have focused on I-PRF applied to the extraction socket and have not explained its effect on AO treatment. In our study, patients diagnosed AO were categorized into 2 groups as I-PRF and control groups. When pain scores were evaluated, it was shown that on the 7th day, pain scores were significantly reduced in the I-PRF group. I-PRF offers unique advantages over conventional PRF, including a higher concentration of leukocytes and growth factors, enhanced anti-inflammatory effects, and a liquid consistency that allows for easier and more uniform application into the socket. Unlike PRF, which forms a solid clot, I-PRF stabilizes within the tissue by forming a fibrin matrix in situ and allows for a sustained release of bioactive components over time. This gradual release may contribute to the more prolonged analgesic effect observed on day 7 in the I-PRF group. The injectable form also eliminates the need for manipulation or compression, thus preserving cellular integrity and improving clinical usability.These features make I-PRF not only a regenerative agent but also a practical, minimally invasive option for clinicians in managing AO, especially in cases where solid membrane placement may be impractical.

The study’s limitations include that it was conducted in a single center and with a smaller patient group. Another limitation of the study is that treatment effectiveness was evaluated solely using VAS scores, which are subjective and may be influenced by individual perception and reporting bias.Additional clinical and functional parameters such as healing rate, soft tissue status, and patient satisfaction were not assessed. Although no side effects were observed in our cohort, the study did not systematically monitor or evaluate potential adverse effects related to I-PRF, which should be considered in future research.

Conclusion

In managing AO, a significant result was found in favor of I-PRF on 7th day when surgical curettage and physiological saline irrigation were applied alone and when I-PRF was added to this procedure. The findings of our prospective study indicate that I-PRF significantly reduces pain in AO patients compared to conventional treatment, and its promising results may offer an alternative treatment option in clinical practice, improving patient outcomes and enhancing pain management strategies. I-PRF shows promising results in reducing pain in AO patients, but confirmatory studies are needed to validate these findings and further evaluate its long-term effectiveness. The findings highlight the clinical potential of I-PRF as a simple, minimally invasive, and biologically based treatment approach. Its autologous origin eliminates the risk of immunological reactions, and its liquid form allows for easy and precise application within the socket. Additionally, I-PRF requires no additives or anticoagulants, is cost-effective, and did not result in any adverse effects in our study. Given its ease of use, affordability, and favorable safety profile, I-PRF may be a valuable adjunct in the clinical management of AO. It can be especially beneficial in outpatient dental settings and in patients who cannot tolerate conventional dressings or medications. Further large-scale, multicenter trials are encouraged to validate these findings and explore the broader applications of I-PRF in oral surgery.

Abbreviations

I-PRF

Injectable platelet-rich fibrin

PRF

Platelet-rich fibrin

CGF

Consantrated growth factor

VAS

Visual analog scale

AO

Alveolar osteitis

Authors’ contributions

All the authors have made substantial contributions to the study. Conceptualization: G.T., S.Ö.T. Formal Analysis: G.T., S.Ö.T. Investigation: G.T., S.Ö.T. Writing—original draft preparation: G.T., S.Ö.T. Writing-review and editing: G.T., S.Ö.T. Supervision: G.T., S.Ö.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by Eskişehir Osmangazi University Clinical Research Ethics Committee (IRB 2024–07(01)) (Approval No:E-80558721-050.04-240189062). The study was carried out in compliance with the principles of the Declaration of Helsinki and the CONSORT (Consolidated Standards of Reporting Trials) guidelines. The study has been registered at clinical trials (ID number NCT06761001). Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.