Background: Pain management is a critical component of orthodontic treatment, often necessitating pharmacological intervention. Nonsteroidal anti-inflammatory drugs are commonly prescribed; however, their mechanism of action involves the inhibition of cyclooxygenase enzymes and prostaglandins, which are essential mediators of bone remodeling. Materials and Methods: A randomized, double-blind clinical trial was conducted with 30 orthodontic patients requiring bilateral maxillary first premolar extractions and subsequent canine retraction. Patients were randomly allocated into two groups: Group A (Ibuprofen, 400 mg) and Group B (Paracetamol, 500 mg), taken thrice daily for 3 days following appliance activation. Canine retraction was performed using nickel–titanium coil springs (150 g force). The rate of tooth movement (mm/month) was measured over 3 months. Gingival crevicular fluid (GCF) samples were analyzed using Enzyme-Linked Immunosorbent Assay. Results: The mean cumulative tooth movement over 3 months was significantly lower in the Ibuprofen group (2.85 ± 0.32 mm) compared to the Paracetamol group (3.45 ± 0.41 mm; P < 0.01). Biochemical analysis revealed that Group A exhibited significantly reduced concentrations of Prostaglandin E2 (145.2 ± 22.1 pg/mL) compared to Group B (210.5 ± 35.4 pg/mL; P < 0.001) at the T1 interval. Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) levels followed a similar trend. Conclusion: Systemic administration of Ibuprofen significantly inhibits the rate of orthodontic tooth movement and suppresses key inflammatory biomarkers necessary for bone resorption. Paracetamol is the preferred analgesic for orthodontic patients as it provides pain relief without interfering with the biological mechanisms of tooth movement.
Alam et al. (2026) studied this question.