Nonsteroidal anti-inflammatory drugs as adjunctive therapy in patients with periodontitis and high caries risk

Relevance. Periodontitis and dental caries are highly prevalent oral diseases that frequently coexist in the context of chronic inflammation. Periodontitis is associated with increased production of inflammatory mediators (IL-1β, IL-6, TNF-α, PGE2, among others), resulting in destruction of periodontal tissues and enhanced enamel demineralization. In this context, the inclusion of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of periodontitis has attracted attention as a means of modulating the immune response. NSAIDs effectively inhibit prostaglandin synthesis and thereby reduce inflammation; however, their effects on clinical periodontal parameters and caries risk require systematic evaluation. Objective: To evaluate the efficacy and safety of systemic and topical administration of five NSAIDs (acetylsalicylic acid, ibuprofen, diclofenac, ketoprofen, and tenoxicam) as adjunctive therapy for chronic periodontitis in adults. Materials and methods. A systematic review of randomized controlled trials and controlled clinical studies published up to March 2024 was conducted in accordance with PRISMA guidelines. The review protocol was registered in PROSPERO (CRD42024518732). Electronic searches were performed in PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Eligible studies included adult patients diagnosed with chronic periodontitis, compared systemic or topical NSAIDs with placebo or standard non-surgical periodontal therapy, with a minimum follow-up of 4 weeks, and reported clinical outcomes such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and related periodontal parameters (Table 2). Risk of bias was assessed using RoB 2 and ROBINS-I tools. Where appropriate, meta-analysis was performed using random-effects models. Results. The literature search identified 876 records, of which 72 articles were assessed in full text; five studies comprising a total of 150 patients met the inclusion criteria, including four randomized controlled trials (RCT) and one controlled nonrandomized study. Adjunctive administration of low-dose acetylsalicylic acid (75–150 mg/day) in combination with non-surgical periodontal therapy over 3–6 months resulted in statistically significant reductions in mean PPD (approximately 0.6 mm) and gains in CAL (approximately 0.5 mm) compared with placebo (p < 0.05). Meta-analysis of three aspirin-based randomized controlled trials demonstrated a significant reduction in PPD (mean difference −0.62 mm; 95% CI −0.78 to −0.45; I2 = 21%) with a moderate level of evidence. Systemic diclofenac provided postoperative analgesia comparable to that of a non-NSAID local analgesic; however, due to the short observation period (3 days), its effects on periodontal parameters were not assessed. Postoperative ibuprofen administration did not improve periodontal healing compared with control treatment and was associated with gastrointestinal complaints in 15% of patients. A 10-day course of tenoxicam (20 mg/day) showed no advantage over placebo with respect to PPD or CAL. No data were identified on systemic ketoprofen use in periodontitis. In contrast, topical NSAID formulations demonstrated beneficial effects: rinsing with a 2% ibuprofen solution three times daily for 12 weeks resulted in an additional reduction in PPD of approximately 0.6 mm and a CAL gain of approximately 0.5 mm without adverse effects; application of a 1.5% ketoprofen gel twice daily for 3 months led to a further reduction in PPD of approximately 0.8 mm (p < 0.05) and a CAL gain of approximately 0.6 mm compared with scaling alone. Application of a 1% diclofenac gel after scaling was associated with a significant clinical attachment gain (+0.4 mm at 3 months). No serious adverse events or ulcerative gastrointestinal bleeding were reported. Topical formulations were well tolerated, with no mucosal irritation observed. Conclusion. Nonsteroidal anti-inflammatory drugs may be effectively used as adjuncts in comprehensive periodontal therapy as modulators of the inflammatory response. Prolonged administration of low-dose aspirin yields moderate but reproducible improvements in key periodontal parameters. Topical NSAID formulations (ibuprofen, ketoprofen, and diclofenac mouthrinses or gels) provide additional periodontal benefits without systemic adverse effects, which is particularly relevant for patients at increased risk of NSAID-associated gastropathy. Incorporation of NSAIDs into treatment protocols for patients with pronounced periodontal inflammation and high caries risk may contribute to suppression of inflammatory tissue destruction and indirectly enhance resistance of dental hard tissues to demineralization. Further high-quality studies are required to determine optimal dosing regimens, treatment duration, and long-term outcomes, including effects on caries activity, before NSAIDs can be recommended for routine inclusion in periodontal treatment standards.

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