Effect of COX-2-Specific Inhibition on Fracture-Healing in the Rat Femur

Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats

“…Additionally, male rats, in which COX-2 inhibitors have shown to have a short half-life and are quickly eliminated [32,50], were used. In Brown et al [8], there were similar findings; indomethacin delayed fracture healing at 4 weeks, but celecoxib, a specific COX-2 inhibitor, did not. Their use of male rats may be a likely explanation for not finding delayed fracture healing in the celecoxib animals.…”

Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry

“…As mentioned for conventional NSAIDs, these apparent controversies cannot be explained by the diversity of experimental parameters alone. For example, while mechanical, radiographic and histological examination revealed the interruption of femoral fracture healing in rats treated with celecoxib (4 mg/kg/day given orally for 2 to 8 weeks) (34), treatment of rats with the same drug (3 mg/kg/day for 4 to 12 weeks, orally) apparently did not interfere with femoral fracture healing, as confirmed by mechanical and radiographic examinations (35). Criticism of experimental models showing deleterious effects by the use of selective NSAIDs on reparative bone formation include the need of further information related to pharmacological dosages for comparison with humanintended therapies, as well as the use of high doses for very long periods, considering their clinical use for intraoperative acute pain control (4,27).…”

“…Data pertaining to selective NSAIDs (celecoxib, rofecoxib, parecoxib) and experimental bone growth are much more recent and less numerous, and despite the importance of COX-2 and PGE 2 for bone formation, the results remain controversial, as are reports referring to the long-term use of selective NSAIDs and impaired reparational bone formation in humans (3,13,14,26,29,(32)(33)(34)(35)(36)(37). As mentioned for conventional NSAIDs, these apparent controversies cannot be explained by the diversity of experimental parameters alone.…”

Efeito dos anti-inflamatórios não-esteroidais convencionais e seletivos para COX-2 sobre o reparo ósseo

“…The majority of the studies show that its long-term use delays long bones repair process and spinal fusion in experimental animals (9,10,11,12,13) . An exception to this is a recent study (14) where neither indomethacin nor other selective and non-selective NSAIDs (ibuprofen, ketorolac, rofecoxib and celecoxib) significantly interfered on tibial repair of mice.…”

“…In addition to the evidences showing that rofecoxib, celecoxib and parecoxib inhibit long bones repair in rats and rabbits (12,17,18,28) , there are some reports stating that rofecoxib and celecoxib do not interfere on long bones' fracture repair and on spinal fusion rates in these species (11,13,14) . Analyzing experimental details, it is not possible to explain these controversies by differences between dosages, forms and time of administration of drugs, by differences between animal species, kind of bone and method of reparative bone tissue assessment.…”