Efficacy and safety of low-dose celecoxib in patients with mild to moderate knee osteoarthritis: a protocol for a single-center, randomized, double-blind, parallel-group controlled trial.

BACKGROUND

Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage degradation and inflammation, leading to pain and functional limitations. Emerging evidence suggests that physiological levels of prostaglandin E2 (PGE2) are crucial for maintaining subchondral bone remodeling balance via skeletal interoception. More and more evidence supports that standard dose or higher doses of celecoxib (≥ 200 mg/day) may disrupt this balance by significantly reducing PGE2 levels, potentially accelerating OA progression. This study aims to compare the efficacy of conventional-dose celecoxib (200 mg/day) versus low-dose celecoxib (100 mg/day) in treating patients with mild to moderate knee OA over a 3-month treatment period and 3-month follow-up.

METHODS

This randomized, double-blind, parallel-group trial will enroll 200 participants diagnosed with mild to moderate knee OA (Kellgren-Lawrence grades I-III), who will be randomized in a 1:1 ratio to receive either conventional (200 mg/day) or low-dose (100 mg/day) celecoxib for consecutive 3 months. After the administration, patients were followed up for 3 months. The primary outcome will be the change in pain intensity, which was measured using the visual analog scale (VAS), from baseline to 24 weeks, evaluated via the VAS. Secondary outcomes include biomarkers of bone metabolism and safety parameters, including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), subchondral bone structure (assessed by high-resolution CT), subchondral bone marrow edema (assessed by MRI), bone turnover markers, and serum levels of PGE2 and COX2. Safety will be assessed by monitoring the incidence and severity of adverse events. We hypothesize that low-dose celecoxib (100 mg/day) is posited to preserve physiological PGE2 levels, maintain skeletal interoception supporting balanced bone remodeling while alleviating pain, and slow the progression of OA.

DISCUSSION: This RCT protocol addresses a critical gap in OA treatment by investigating the potential of low-dose celecoxib to balance pain management with disease modification. By preserving physiological PGE2 levels and skeletal interoception, low-dose celecoxib may offer a safer and more effective alternative to standard-dose treatment, particularly for patients with I-III grade OA.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400080744. Registered on February 6, 2024.