Mehmet MÜFİT ORAK, Dursun AK, AHMET MİDİ, BERNA LAÇİN, Sevim PURİSA, GÜVEN BULUT

Comparison of the effects of chronic intra-articular administration of tenoxicam, diclofenac, and methylprednisolone in healthy rats

Objective: Lyophilized drug manufacturing and intra-articular (IA) applications have increased to address gastrointestinal side effects resulting from chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) for degenerative joint disease. Accordingly, we histologically examined joint and stomach tissues from rats to determine and compare the effects of long-term treatment with an IA corticosteroid (methylprednisolone acetate), lyophilized NSAID (tenoxicam), and non-lyophilized NSAID (diclofenac) following application to the knee joint.Methods: One hundred Wistar albino rats were divided into 4 groups of 25 rats: control, methylprednisolone, tenoxicam, and diclofenac. Ten IA injections were administered at 1-week intervals. Rats were sacrificed at 48 h and 1, 2, 4, and 8 weeks after the tenth injection. Histomorphologically, knee joint samples were examined for osteoarthritic changes and stomach tissue samples for gastric changes.Results: Unlike methylprednisolone, diclofenac and tenoxicam caused increased fibrosis and fibroblast production; furthermore, chronic methylprednisolone use had no negative effects on the synovium or cartilage.Conclusion: Chronic tenoxicam and diclofenac use affects joints more negatively than chronic steroid treatment

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Brandt KD. Diagnosis and nonsurgical management of os- teoarthritis. First Edition. Caddo, OK: Professional Com- munications, Inc. 1996. [ISBN: 1-884735-09-6]

Cook TM, Tuckey JP, Nolan JP. Analgesia after day-case knee arthroscopy: double-blind study of intra-articular tenoxicam, intra-articular bupivacaine and placebo. Br J Anaesth 1997;78:163-8.

Colbert ST, Curran E, O'Hanlon DM, Moran R, Mc- Carroll M. Intra-articular tenoxicam improves post- operative analgesia in knee arthroscopy. Can J Anaesth 1999;46:653-7.

Uthman I, Raynauld JP, Haraoui B. Intra-articular therapy in osteoarthritis. Postgrad Med J 2003;79:449-53.

Ozyuvaci H, Bilgic B, Ozyuvaci E, Altan A, Altug T, Ka- raca C. Intra-articular injection of tenoxicam in rats: as- sessment of the local effects on the articular cartilage and synovium. J Int Med Res 2004;32:312-6.

Peckett WR, Butler-Manuel A. Intra-articular steroids af- ter arthroscopy for osteoarthritis of the knee. J Bone Joint Surg Br 2000;82:775-6.

Brandt KD. Management of osteoartritis. In Ruddy S, Ha- ris ED Jr, Sledge CB, editors. Kelley's Texbook of Rheu- matology. 6th ed. Philadelphia: W.B. Saunders Company 2001. pp. 1419-32.

Recommendations for the medical management of osteo- arthritis of the hip and knee: 2000 update. American Col- lege of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905-15.

Riggin CN, Tucker JJ, Soslowsky LJ, Kuntz AF. Intra-ar- ticular tibiofemoral injection of a nonsteroidal anti-inflam- matory drug has no detrimental effects on joint mechanics in a rat model. J Orthop Res 2014;32:1512-9.

Blot L, Marcelis A, Devogelaer JP, Manicourt DH. Effects of diclofenac, aceclofenac and meloxicam on the metabo- lism of proteoglycans and hyaluronan in osteoarthritic hu- man cartilage. Br J Pharmacol 2000;131:1413-21.

Ding C. Do NSAIDs affect the progression of osteoarthri- tis? Inflammation 2002;26:139-42.

Notoya K, Jovanovic DV, Reboul P, Martel-Pelletier J, Mineau F, Pelletier JP. The induction of cell death in hu- man osteoarthritis chondrocytes by nitric oxide is related to the production of prostaglandin E2 via the induction of cyclooxygenase-2. J Immunol 2000;165:3402-10.

Henroitin Y, Reginster JY. In-vitro differences among non- steroidal antiinflammatory drugs in their activities related to osteoarthritis pathophysiology. Osteoarthritis Cartilage 1999;7:355-7.

Mukherjee P, Rachita C, Aisen PS, Pasinetti GM. Non- steroidal anti-inflammatory drugs protect against chon- drocyte apoptotic death. Clin Exp Rheumatol 2001;19(1 Suppl 22):7-11.

Guler G, Karaoglu S, Velibasoglu H, Ramazanogullari N, Boyaci A. Comparison of analgesic effects of intra-articu- lar tenoxicam and morphine in anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 2002;10:229-32.

Oztuna V, Eskandari M, Bugdayci R, Kuyurtar F. Intra-ar- ticular injection of tenoxicam in osteoarthritic knee joints with effusion. Orthopedics 2007;30:1039-42.

Kirdemir P, Marsan A, Gogus N, Tabak Y, Tekin M. Com- parison between the analgesic effects of intraarticular neo- stigmine, tramadol and tenoxicam. Acta Orthop Trauma- tol Turc 2001;35:358-62.

Elhakim M, Nafie M, Eid A, Hassin M. Combination of intra-articular tenoxicam, lidocaine, and pethidine for outpatient knee arthroscopy. Acta Anaesthesiol Scand 1999;43:803-8.

Saricaoglu F, Dal D, Atilla P, Iskit AB, Tarhan O, Aşan E, et al. Effect of intraarticular injection of lornoxicam on the articular cartilage & synovium in rat. Indian J Med Res 2008;127:362-5.

Lane NE, Thompson JM. Management of osteoarthritis in the primary-care setting: an evidence-based approach to treatment. Am J Med 1997;103:25-30.

Godwin M, Dawes M. Intra-articular steroid injections for painful knees. Systematic review with meta-analysis. Can Fam Physician 2004;50:241-8.

Pelletier JP, Martel-Pelletier J. Recent developments in the therapy of osteoarthritis. In: Tsokos GC, editor. Modern Therapeutics in Rheumatic Diseases. Totowa, NJ: Huma- na Press; 2002. pp. 253-5.

Pasquali Ronchetti I, Guerra D, Taparelli F, Boraldi F, Bergamini G, Mori G, et al. Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan) and methylprednisolone acetate (Depomedrol) in osteoarthritis. Rheumatology (Oxford) 2001;40:158-69.

Gosal HS, Jackson AM, Bickerstaff DR. Intra-articular steroids after arthroscopy for osteoarthritis of the knee. J Bone Joint Surg Br 1999;81:952-4.

Ratiner B, Gramas DA, Lane NE. Osteoarthritis. In: Weisman MH, Weinblatt ME, Louis JS, editors. Treat- ment of the Rheumatic Diseases. Companion to Kelley's Textbook of Rheumatology. 2nd ed. Philadelphia: W.B. Saunders Company; 2001. pp. 461-86.

Ayral X. Injections in the treatment of osteoarthritis. Best Pract Res Clin Rheumatol 2001;15:609-26.

Creamer P. Intra-articular corticosteroid injections in os- teoarthritis: do they work and if so, how? Ann Rheum Dis 1997;56:634-6.

Gossec L, Dougados M. Intra-articular treatments in os- teoarthritis: from the symptomatic to the structure modi- fying. Ann Rheum Dis 2004;63:478-82.

Gossec L, Dougados M. Do intra-articular therapies work and who will benefit most? Best Pract Res Clin Rheumatol 2006;20:131-44.

Kirwan J. Is there a place for intra-articular hyaluronate in osteoarthritis of the knee? Knee 2001;8:93-101.

Kirwan JR, Rankin E. Intra-articular therapy in osteoar- thritis. Baillieres Clin Rheumatol 1997;11:769-94.

Schumacher HR, Chen LX. Injectable corticoste

roids in treatment of arthritis of the knee. Am J Med 2005;118:1208-14.

Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui B, Martel-Pelletier J, et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthri- tis of the knee: a randomized, double-blind, placebo-con- trolled trial. Arthritis Rheum 2003;48:370-7.

Jaffré B, Watrin A, Loeuille D, Gillet P, Netter P, Laugier P, et al. Effects of antiinflammatory drugs on arthritic car- tilage: a high-frequency quantitative ultrasound study in rats. Arthritis Rheum 2003;48:1594-601.