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Published in: Sports Medicine 4/2005

01-04-2005 | Leading Article

Cyclo-Oxygenase-2 Inhibitors

Beneficial or Detrimental for Athletes with Acute Musculoskeletal Injuries?

Author: Stuart J. Warden

Published in: Sports Medicine | Issue 4/2005

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Abstract

The major goal of clinicians when treating acute musculoskeletal injuries is to return athletes to their pre-injury level of function, ideally in the shortest time possible and without compromising tissue-level healing. In this regard, a commonly used intervention is the taking of NSAIDs. These are used to limit the amount and duration of inflammation, and to control pain. While NSAIDs have become synonymous with the management of acute musculoskeletal injuries, their efficacy has yet to be proven. This is of particular concern in view of recent research investigating the latest class of NSAIDs — selective cyclo-oxygenase-2 inhibitors (COXIBs). COXIBs were developed to reduce the adverse gastrointestinal (GI) effects of traditional NSAIDs. While they have beneficial anti-inflammatory and analgesic properties, and appear to facilitate earlier return to function following acute injury, the effect of COXIBs on tissue-level healing is currently unknown. In experimental animal models of acute injury, COXIBs have been shown to be detrimental to tissue-level repair. Specifically, they have been shown to impair mechanical strength return following acute injury to bone, ligament and tendon. Clinically, this may have implications for ongoing morbidity and future injury susceptibility. However, the current animal studies have limited translation to the clinical setting, particularly because of significant limitations relating to drug use and dosage in these studies.
There is currently no randomised, controlled trial evidence of the tissue-level effects of COXIBs on acute musculoskeletal injuries. In addition to questions relating to the effect of COXIBs on tissue-level healing, further questions regarding the use of these agents have been raised given a recent link being shown between one COXIB (rofecoxib) and an increased risk for adverse cardiovascular events. Whether this finding is related to the individual properties of rofecoxib or is a class phenomenon is the subject of ongoing investigation. However, in light of the potential risks associated with using COXIBs, an acceptable and possibly safer alternative in the management of acute musculoskeletal injuries may be to use traditional NSAIDs. Traditional NSAIDs do carry the potential for greater adverse GI effects and their clinical effects on tissue-level healing remain relatively unknown. However, they do not appear to be associated with adverse cardiovascular effects, and they are effective pain relievers and cheaper alternatives.
Literature
2.
go back to reference Kannus P, Parkkari J, Jarvinen TL, et al. Basic science and clinical studies coincide: active treatment approach is needed after a sports injury. Scand J Med Sci Sports 2003; 13: 150–4PubMedCrossRef Kannus P, Parkkari J, Jarvinen TL, et al. Basic science and clinical studies coincide: active treatment approach is needed after a sports injury. Scand J Med Sci Sports 2003; 13: 150–4PubMedCrossRef
4.
go back to reference Almekinders LC. Anti-inflammatory treatment of muscular injuries in sport: an update of recent studies. Sports Med 1999; 28: 383–8PubMedCrossRef Almekinders LC. Anti-inflammatory treatment of muscular injuries in sport: an update of recent studies. Sports Med 1999; 28: 383–8PubMedCrossRef
5.
go back to reference Ankarath S, Raman R, Giannoudis PV. Non-steriodal anti-inflammatory drugs in orthopaedic practice: an update. Curr Orthop 2003; 17: 144–9CrossRef Ankarath S, Raman R, Giannoudis PV. Non-steriodal anti-inflammatory drugs in orthopaedic practice: an update. Curr Orthop 2003; 17: 144–9CrossRef
6.
go back to reference Baldwin Lanier A. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury. Sports Med 2003; 33: 177–85PubMedCrossRef Baldwin Lanier A. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury. Sports Med 2003; 33: 177–85PubMedCrossRef
7.
go back to reference Dahners LE, Mullis BH. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. J Am Acad Orthop Surg 2004; 12: 139–43PubMed Dahners LE, Mullis BH. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. J Am Acad Orthop Surg 2004; 12: 139–43PubMed
8.
go back to reference Harder AT, An YH. The mechanisms of the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone healing: a concise review. J Clin Pharmacol 2003; 43: 807–15PubMedCrossRef Harder AT, An YH. The mechanisms of the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone healing: a concise review. J Clin Pharmacol 2003; 43: 807–15PubMedCrossRef
9.
go back to reference Leadbetter WB. Anti-inflammatory therapy in sports injury: the role of nonsteroidal drugs and corticosteroid injection. Clin Sports Med 1995; 14: 353–410PubMed Leadbetter WB. Anti-inflammatory therapy in sports injury: the role of nonsteroidal drugs and corticosteroid injection. Clin Sports Med 1995; 14: 353–410PubMed
10.
go back to reference Stovitz SD, Johnson RJ. NSAIDs and musculoskeletal treatment: what is the clinical evidence? Phys Sportsmed 2003; 31: 35–40, 52 Stovitz SD, Johnson RJ. NSAIDs and musculoskeletal treatment: what is the clinical evidence? Phys Sportsmed 2003; 31: 35–40, 52
11.
go back to reference Weiler JM. Medical modifiers of sports injury: the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. Clin Sports Med 1992; 11: 625–44PubMed Weiler JM. Medical modifiers of sports injury: the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in sports soft-tissue injury. Clin Sports Med 1992; 11: 625–44PubMed
12.
go back to reference Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971; 231: 232–5PubMed Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971; 231: 232–5PubMed
13.
go back to reference Wen PZ, Warden C, Fletcher BS, et al. Chromosomal organization of the inducible and constitutive prostaglandin synthase/cyclooxygenase genes in mouse. Genomics 1993; 15: 458–60PubMedCrossRef Wen PZ, Warden C, Fletcher BS, et al. Chromosomal organization of the inducible and constitutive prostaglandin synthase/cyclooxygenase genes in mouse. Genomics 1993; 15: 458–60PubMedCrossRef
14.
go back to reference Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and -2. Adv Immunol 1996; 62: 167–215PubMedCrossRef Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and -2. Adv Immunol 1996; 62: 167–215PubMedCrossRef
15.
go back to reference Marnett LJ, Rowlinson SW, Goodwin DC, et al. Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. J Biol Chem 1999; 274: 22903–6PubMedCrossRef Marnett LJ, Rowlinson SW, Goodwin DC, et al. Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. J Biol Chem 1999; 274: 22903–6PubMedCrossRef
16.
17.
go back to reference Mitchell JA, Larkin S, Williams TJ. Cyclooxygenase-2: regulation and relevance in inflammation. Biochem Pharmacol 1995; 50: 1535–42PubMedCrossRef Mitchell JA, Larkin S, Williams TJ. Cyclooxygenase-2: regulation and relevance in inflammation. Biochem Pharmacol 1995; 50: 1535–42PubMedCrossRef
18.
go back to reference Cirino G. Multiple controls in inflammation: extracellular and intracellular phospholipase A2, inducible and constitutive cyclooxygenase, and inducible nitric oxide synthase. Biochem Pharmacol 1998; 55: 105–11PubMedCrossRef Cirino G. Multiple controls in inflammation: extracellular and intracellular phospholipase A2, inducible and constitutive cyclooxygenase, and inducible nitric oxide synthase. Biochem Pharmacol 1998; 55: 105–11PubMedCrossRef
19.
go back to reference Blain H, Boileau C, Lapicque F, et al. Limitation of the in vitro whole blood assay for predicting the COX selectivity of NSAIDs in clinical use. Br J Clin Pharmacol 2002; 53: 255–65PubMedCrossRef Blain H, Boileau C, Lapicque F, et al. Limitation of the in vitro whole blood assay for predicting the COX selectivity of NSAIDs in clinical use. Br J Clin Pharmacol 2002; 53: 255–65PubMedCrossRef
20.
go back to reference Chan CC, Boyce S, Brideau C, et al. Rofecoxib [Vioxx, MK-0966; 4-(4’-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther 1999; 290: 551–60PubMed Chan CC, Boyce S, Brideau C, et al. Rofecoxib [Vioxx, MK-0966; 4-(4’-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. J Pharmacol Exp Ther 1999; 290: 551–60PubMed
21.
go back to reference Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104: 413–21PubMedCrossRef Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104: 413–21PubMedCrossRef
22.
go back to reference Patrono C, Patrignani P, Garcia Rodriguez LA. Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs. J Clin Invest 2001; 108: 7–13PubMed Patrono C, Patrignani P, Garcia Rodriguez LA. Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs. J Clin Invest 2001; 108: 7–13PubMed
23.
go back to reference Riendeau D, Percival MD, Brideau C, et al. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther 2001; 296: 558–66PubMed Riendeau D, Percival MD, Brideau C, et al. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther 2001; 296: 558–66PubMed
24.
go back to reference Tacconelli S, Capone ML, Sciulli MG, et al. The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity. Curr Med Res Opin 2002; 18: 503–11PubMedCrossRef Tacconelli S, Capone ML, Sciulli MG, et al. The biochemical selectivity of novel COX-2 inhibitors in whole blood assays of COX-isozyme activity. Curr Med Res Opin 2002; 18: 503–11PubMedCrossRef
25.
go back to reference Talley JJ, Brown DL, Carter JS, et al. 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J Med Chem 2000; 43: 775–7PubMedCrossRef Talley JJ, Brown DL, Carter JS, et al. 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. J Med Chem 2000; 43: 775–7PubMedCrossRef
26.
go back to reference Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A 1999; 96: 7563–8PubMedCrossRef Warner TD, Giuliano F, Vojnovic I, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A 1999; 96: 7563–8PubMedCrossRef
27.
go back to reference Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–99PubMedCrossRef Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–99PubMedCrossRef
28.
go back to reference FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345: 433–42PubMedCrossRef FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345: 433–42PubMedCrossRef
29.
go back to reference Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343: 1520–8PubMedCrossRef Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343: 1520–8PubMedCrossRef
30.
go back to reference Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284: 1247–55PubMedCrossRef Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284: 1247–55PubMedCrossRef
31.
go back to reference Bassett K, Wright JM, Puil L, et al. Cyclooxygenase-2 inhibitor update: journal publications fail to tell the full story. Can Fam Physician 2002; 48: 1455–60PubMed Bassett K, Wright JM, Puil L, et al. Cyclooxygenase-2 inhibitor update: journal publications fail to tell the full story. Can Fam Physician 2002; 48: 1455–60PubMed
32.
go back to reference Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ 2002; 325: 619PubMedCrossRef Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ 2002; 325: 619PubMedCrossRef
33.
go back to reference Watson DJ, Harper SE, Zhao PL, et al. Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 2000; 160: 2998–3003PubMedCrossRef Watson DJ, Harper SE, Zhao PL, et al. Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 2000; 160: 2998–3003PubMedCrossRef
34.
go back to reference Gerstenfeld LC, Einhorn TA. COX inhibitors and their effects on bone healing. Expert Opin Drug Saf 2004; 3: 131–6PubMedCrossRef Gerstenfeld LC, Einhorn TA. COX inhibitors and their effects on bone healing. Expert Opin Drug Saf 2004; 3: 131–6PubMedCrossRef
35.
36.
go back to reference Einhorn TA. Do inhibitors of cyclooxygenase-2 impair bone healing? J Bone Miner Res 2002; 17: 977–8PubMedCrossRef Einhorn TA. Do inhibitors of cyclooxygenase-2 impair bone healing? J Bone Miner Res 2002; 17: 977–8PubMedCrossRef
37.
go back to reference Brown KM, Saunders MM, Kirsch T, et al. Effect of COX-2-specific inhibition on fracture-healing in the rat femur. J Bone Joint Surg Am 2004; 86-A: 116–23PubMed Brown KM, Saunders MM, Kirsch T, et al. Effect of COX-2-specific inhibition on fracture-healing in the rat femur. J Bone Joint Surg Am 2004; 86-A: 116–23PubMed
38.
go back to reference Cohen DB, Kawamura S, Ehteshami JR, et al. Inhibitory effects of traditional NSAIDs and cyclooxygenase-2 inhibitors on rotator cuff tendon healing. Transactions of the 50th Annual Meeting of the Orthopaedic Research Society; 2004 Mar 7–10; San Francisco (CA). Rosemont (IL): Orthopaedic Research Society, 2004: 207 Cohen DB, Kawamura S, Ehteshami JR, et al. Inhibitory effects of traditional NSAIDs and cyclooxygenase-2 inhibitors on rotator cuff tendon healing. Transactions of the 50th Annual Meeting of the Orthopaedic Research Society; 2004 Mar 7–10; San Francisco (CA). Rosemont (IL): Orthopaedic Research Society, 2004: 207
39.
go back to reference Elder CL, Dahners LE, Weinhold PS. A cyclooxygenase-2 inhibitor impairs ligament healing in the rat. Am J Sports Med 2001; 29: 801–5PubMed Elder CL, Dahners LE, Weinhold PS. A cyclooxygenase-2 inhibitor impairs ligament healing in the rat. Am J Sports Med 2001; 29: 801–5PubMed
40.
go back to reference Endo K, Sairyo K, Komatsubara S, et al. Cyclooxygenase-2 inhibitor inhibits the fracture healing. J Physiol Anthropol Appl Human Sci 2002; 21: 235–8PubMedCrossRef Endo K, Sairyo K, Komatsubara S, et al. Cyclooxygenase-2 inhibitor inhibits the fracture healing. J Physiol Anthropol Appl Human Sci 2002; 21: 235–8PubMedCrossRef
41.
go back to reference Gerstenfeld LC, Thiede M, Seibert K, et al. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs. J Orthop Res 2003; 21: 670–5PubMedCrossRef Gerstenfeld LC, Thiede M, Seibert K, et al. Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs. J Orthop Res 2003; 21: 670–5PubMedCrossRef
42.
go back to reference Prisk V, Foster W, Li Y, et al. The effects of cyclooxygenase-2 inhibition on skeletal muscle healing. Transactions of the 50th Annual Meeting of the Orthopaedic Research Society; 2004 Mar 7–10; San Francisco (CA). Rosemont (IL): Orthopaedic Research Society, 2004: 905 Prisk V, Foster W, Li Y, et al. The effects of cyclooxygenase-2 inhibition on skeletal muscle healing. Transactions of the 50th Annual Meeting of the Orthopaedic Research Society; 2004 Mar 7–10; San Francisco (CA). Rosemont (IL): Orthopaedic Research Society, 2004: 905
43.
go back to reference Simon AM, Manigrasso MB, O’Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res 2002; 17: 963–76PubMedCrossRef Simon AM, Manigrasso MB, O’Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res 2002; 17: 963–76PubMedCrossRef
44.
go back to reference Allen HL, Wase A, Bear WT. Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand 1980; 51: 595–600PubMedCrossRef Allen HL, Wase A, Bear WT. Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand 1980; 51: 595–600PubMedCrossRef
45.
go back to reference Lindholm TS, Tornkvist H. Inhibitory effect on bone formation and calcification exerted by the anti-inflammatory drug ibuprofen: an experimental study on adult rat with fracture. Scand J Rheumatol 1981; 10: 38–42PubMed Lindholm TS, Tornkvist H. Inhibitory effect on bone formation and calcification exerted by the anti-inflammatory drug ibuprofen: an experimental study on adult rat with fracture. Scand J Rheumatol 1981; 10: 38–42PubMed
46.
go back to reference Zhang X, Schwarz EM, Young DA, et al. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 2002; 109: 1405–15PubMed Zhang X, Schwarz EM, Young DA, et al. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 2002; 109: 1405–15PubMed
47.
go back to reference Forslund C, Bylander B, Aspenberg P. Indomethacin and celecoxib improve tendon healing in rats. Acta Orthop Scand 2003; 74: 465–9PubMedCrossRef Forslund C, Bylander B, Aspenberg P. Indomethacin and celecoxib improve tendon healing in rats. Acta Orthop Scand 2003; 74: 465–9PubMedCrossRef
48.
go back to reference Virchenko O, Skoglund B, Aspenberg P. Parecoxib impairs early tendon repair but improves later remodeling. Am J Sports Med 2004; 32: 1743–7PubMedCrossRef Virchenko O, Skoglund B, Aspenberg P. Parecoxib impairs early tendon repair but improves later remodeling. Am J Sports Med 2004; 32: 1743–7PubMedCrossRef
49.
go back to reference Lapointe BM, Fremont P, Cote CH. Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Am J Physiol Regul Integr Comp Physiol 2002; 282: R323–9 Lapointe BM, Fremont P, Cote CH. Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Am J Physiol Regul Integr Comp Physiol 2002; 282: R323–9
51.
go back to reference Zhang J, Goorha S, Raghow R, et al. The tissue-specific, compensatory expression of cyclooxygenase-1 and -2 in transgenic mice. Prostaglandins Other Lipid Mediat 2002; 67: 121–35PubMedCrossRef Zhang J, Goorha S, Raghow R, et al. The tissue-specific, compensatory expression of cyclooxygenase-1 and -2 in transgenic mice. Prostaglandins Other Lipid Mediat 2002; 67: 121–35PubMedCrossRef
52.
go back to reference Alam I, Warden SJ, Robling AG, et al. Mechanotransduction in bone does not require a functional cyclooxygenase-2 (COX-2) gene. J Bone Miner Res 2005; 20: 438–46PubMedCrossRef Alam I, Warden SJ, Robling AG, et al. Mechanotransduction in bone does not require a functional cyclooxygenase-2 (COX-2) gene. J Bone Miner Res 2005; 20: 438–46PubMedCrossRef
53.
go back to reference Dinchuk JE, Car BD, Focht RJ, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 1995; 378: 406–9PubMedCrossRef Dinchuk JE, Car BD, Focht RJ, et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 1995; 378: 406–9PubMedCrossRef
54.
go back to reference Morham SG, Langenbach R, Loftin CD, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 1995; 83: 473–82PubMedCrossRef Morham SG, Langenbach R, Loftin CD, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 1995; 83: 473–82PubMedCrossRef
55.
go back to reference Laulederkind SJ, Wall BM, Ballou LR, et al. Renal pathology resulting from PGHS-2 gene ablation in DBA/B6 mice. Prostaglandins Other Lipid Mediat 2002; 70: 161–8PubMedCrossRef Laulederkind SJ, Wall BM, Ballou LR, et al. Renal pathology resulting from PGHS-2 gene ablation in DBA/B6 mice. Prostaglandins Other Lipid Mediat 2002; 70: 161–8PubMedCrossRef
56.
go back to reference O’Connor JP, Simon AM. Sustained inhibition of COX-2 decreases fracture healing success. J Bone Miner Res 2003; 18 Suppl. 2: S338 O’Connor JP, Simon AM. Sustained inhibition of COX-2 decreases fracture healing success. J Bone Miner Res 2003; 18 Suppl. 2: S338
57.
go back to reference Gerstenfeld LC, Cullinane DM, Krall EA, et al. COX-2 inhibitors and fracture healing: reversibility of effects after short term treatment. J Bone Miner Res 2003; 18 Suppl. 2: S43 Gerstenfeld LC, Cullinane DM, Krall EA, et al. COX-2 inhibitors and fracture healing: reversibility of effects after short term treatment. J Bone Miner Res 2003; 18 Suppl. 2: S43
58.
go back to reference Gilroy DW, Colville-Nash PR, Willis D, et al. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 1999; 5: 698–701PubMedCrossRef Gilroy DW, Colville-Nash PR, Willis D, et al. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 1999; 5: 698–701PubMedCrossRef
59.
go back to reference Davies NM, McLachlan AJ, Day RO, et al. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2000; 38: 225–42PubMedCrossRef Davies NM, McLachlan AJ, Day RO, et al. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2000; 38: 225–42PubMedCrossRef
60.
go back to reference Davies NM, Teng XW, Skjodt NM. Pharmacokinetics of rofecoxib: a specific cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2003; 42: 545–56PubMedCrossRef Davies NM, Teng XW, Skjodt NM. Pharmacokinetics of rofecoxib: a specific cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2003; 42: 545–56PubMedCrossRef
61.
go back to reference Paulson SK, Zhang JY, Breau AP, et al. Pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib in rats. Drug Metab Dispos 2000; 28: 514–21PubMed Paulson SK, Zhang JY, Breau AP, et al. Pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib in rats. Drug Metab Dispos 2000; 28: 514–21PubMed
62.
go back to reference Paulson SK, Hribar JD, Liu NW, et al. Metabolism and excretion of [14C]celecoxib in healthy male volunteers. Drug Metab Dispos 2000; 28: 308–14PubMed Paulson SK, Hribar JD, Liu NW, et al. Metabolism and excretion of [14C]celecoxib in healthy male volunteers. Drug Metab Dispos 2000; 28: 308–14PubMed
63.
go back to reference Halpin RA, Geer LA, Zhang KE, et al. The absorption, distribution, metabolism and excretion of rofecoxib, a potent and selective cyclooxygenase-2 inhibitor, in rats and dogs. Drug Metab Dispos 2000; 28: 1244–54PubMed Halpin RA, Geer LA, Zhang KE, et al. The absorption, distribution, metabolism and excretion of rofecoxib, a potent and selective cyclooxygenase-2 inhibitor, in rats and dogs. Drug Metab Dispos 2000; 28: 1244–54PubMed
64.
go back to reference Depré M, Ehrich E, Van Hecken A, et al. Pharmacokinetics, COX-2 specificity, and tolerability of supratherapeutic doses of rofecoxib in humans. Eur J Clin Pharmacol 2000; 56: 167–74PubMedCrossRef Depré M, Ehrich E, Van Hecken A, et al. Pharmacokinetics, COX-2 specificity, and tolerability of supratherapeutic doses of rofecoxib in humans. Eur J Clin Pharmacol 2000; 56: 167–74PubMedCrossRef
65.
go back to reference Werner U, Werner D, Mundkowski R, et al. Selective and rapid liquid chromatography-mass spectrometry method for the quantification of rofecoxib in pharmacokinetic studies with humans. J Chromatogr B Biomed Sci Appl 2001; 760: 83–90PubMedCrossRef Werner U, Werner D, Mundkowski R, et al. Selective and rapid liquid chromatography-mass spectrometry method for the quantification of rofecoxib in pharmacokinetic studies with humans. J Chromatogr B Biomed Sci Appl 2001; 760: 83–90PubMedCrossRef
66.
go back to reference Giannoudis PV, MacDonald DA, Matthews SJ, et al. Nonunion of the femoral diaphysis: the influence of reaming and non-steroidal anti-inflammatory drugs. J Bone Joint Surg Br 2000; 82-B: 655–8PubMedCrossRef Giannoudis PV, MacDonald DA, Matthews SJ, et al. Nonunion of the femoral diaphysis: the influence of reaming and non-steroidal anti-inflammatory drugs. J Bone Joint Surg Br 2000; 82-B: 655–8PubMedCrossRef
67.
go back to reference Glassman SD, Rose SM, Dimar JR, et al. The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 1998; 23: 834–8PubMedCrossRef Glassman SD, Rose SM, Dimar JR, et al. The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 1998; 23: 834–8PubMedCrossRef
68.
go back to reference Ekman EF, Fiechtner JJ, Levy S, et al. Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain. Am J Orthop 2002; 31: 445–51PubMed Ekman EF, Fiechtner JJ, Levy S, et al. Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain. Am J Orthop 2002; 31: 445–51PubMed
69.
go back to reference Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003; 290: 2411–8PubMedCrossRef Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003; 290: 2411–8PubMedCrossRef
70.
go back to reference Slatyer MA, Hensley MJ, Lopert R. A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med 1997; 25: 544–53PubMedCrossRef Slatyer MA, Hensley MJ, Lopert R. A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study. Am J Sports Med 1997; 25: 544–53PubMedCrossRef
72.
go back to reference Bresalier R, Lanas A, Morton D, et al. Rofecoxib APPROVe study results and their implications. 68th Annual Scientific Meeting, American College of Rheumatology/Association of Rheumatology Health Professionals; 2004 Oct 16–21; San Antonio (TX) Bresalier R, Lanas A, Morton D, et al. Rofecoxib APPROVe study results and their implications. 68th Annual Scientific Meeting, American College of Rheumatology/Association of Rheumatology Health Professionals; 2004 Oct 16–21; San Antonio (TX)
73.
go back to reference FitzGerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2003; 2: 879–90PubMedCrossRef FitzGerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2003; 2: 879–90PubMedCrossRef
74.
go back to reference FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol 1991; 68: 11B-5BCrossRef FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol 1991; 68: 11B-5BCrossRef
75.
go back to reference McAdam BF, Catella-Lawson F, Mardini IA, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 1999; 96: 272–7PubMedCrossRef McAdam BF, Catella-Lawson F, Mardini IA, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 1999; 96: 272–7PubMedCrossRef
76.
77.
go back to reference Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71–86CrossRef Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71–86CrossRef
78.
go back to reference Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002; 296: 539–41PubMedCrossRef Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002; 296: 539–41PubMedCrossRef
79.
go back to reference Couzin J. Drug safety: withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science 2004; 306: 384–5PubMedCrossRef Couzin J. Drug safety: withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science 2004; 306: 384–5PubMedCrossRef
81.
go back to reference Frantz S. Vioxx risk signifies trouble in class. Nat Rev Drug Discov 2004; 3: 899–901PubMed Frantz S. Vioxx risk signifies trouble in class. Nat Rev Drug Discov 2004; 3: 899–901PubMed
82.
go back to reference Mamdani M, Juurlink DN, Lee DS, et al. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet 2004; 363: 1751–6PubMedCrossRef Mamdani M, Juurlink DN, Lee DS, et al. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet 2004; 363: 1751–6PubMedCrossRef
84.
go back to reference Mamdani M, Rochon P, Juurlink DN, et al. Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med 2003; 163: 481–6PubMedCrossRef Mamdani M, Rochon P, Juurlink DN, et al. Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly. Arch Intern Med 2003; 163: 481–6PubMedCrossRef
85.
go back to reference Petrella R, Ekman EF, Schuller R, et al. Efficacy of celecoxib, a COX-2-specific inhibitor, and naproxen in the management of acute ankle sprain: results of a double-blind, randomized controlled trial. Clin J Sport Med 2004; 14: 225–31PubMedCrossRef Petrella R, Ekman EF, Schuller R, et al. Efficacy of celecoxib, a COX-2-specific inhibitor, and naproxen in the management of acute ankle sprain: results of a double-blind, randomized controlled trial. Clin J Sport Med 2004; 14: 225–31PubMedCrossRef
Metadata
Title
Cyclo-Oxygenase-2 Inhibitors
Beneficial or Detrimental for Athletes with Acute Musculoskeletal Injuries?
Author
Stuart J. Warden
Publication date
01-04-2005
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 4/2005
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.2165/00007256-200535040-00001