Osteoarthritis — an untreatable disease? (original) (raw)
Harris, E. D. Jr. The Bone and Joint decade: a catalyst for progress. Arthritis Rheum44, 1969–1970 (2004). Article Google Scholar
WHO Scientific group. The burden of musculoskeletal conditions at the start of the new millennium. World Health Organ Tech. Rep. Ser.919, 1–218 (2003). The tremendous challenge of the disease is summarized in this report of the epidemiology of musculoskeletal diseases.
NIH Consensus Statement on Total Knee Replacement December 8–10, 2003. J. Bone Joint Surg. Am.86, 1328–1335 (2004).
Kean, W. F., Kean, R. & Buchanan, W. W. Osteoarthritis: symptoms, signs and source of pain. Inflammo-pharmacology12, 3–31 (2004). ArticleCASPubMed Google Scholar
Badley, E. M. & Wang, P. P. Arthritis and the aging population: projections of arthritis prevalence in Canada 1991 to 2031. J. Rheumatol.25, 138–144 (1998). CASPubMed Google Scholar
Decision Resources, Inc. Osteoarthritis: Immune and Inflammatory Disorders Study (Decision Resources, Inc., Waltham, Massachusetts, 2004).
Hannan, M. T., Felson, D. T. & Pincus, T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J. Rheumatol.27, 1513–1517 (2000). CASPubMed Google Scholar
Flower, R. J. The development of COX2 inhibitors. Nature Rev. Drug. Discov.2, 179–191 (2003). A comprehensive review of COX2 inhibitor development. ArticleCAS Google Scholar
Topol, E. J. Failing the public health — Rofecoxib, Merck, and the FDA. N. Engl. J. Med.351, 1707–1711 (2004). ArticleCASPubMed Google Scholar
Petit-Zeman, S. Characteristics of COX 2 inhibitors questioned. Nature Rev. Drug. Discov.3, 726–727 (2004). This paper and reference10 provide evidence that the safety of COX2 inhibitors will be re-evaluated. ArticleCAS Google Scholar
Felson, D. T. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol. Clin. N. Am.42, 1–9 (2004). ArticlePubMed Google Scholar
Spector, T. D. & MacGregor, A. J. Risk factors for osteoarthritis: genetics. Osteoarthr. Cartil.12, S39–S44 (2004). ArticlePubMed Google Scholar
Richette, P. & Bardin, T. Structure-modifying agents for osteoarthritis: an update. Joint Bone Spine71, 18–23 (2004). ArticlePubMed Google Scholar
Jordan, K. M. et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann. Rheum. Dis.62, 1145–1155 (2003). Recent clinical recommendations issued by an osteoarthritis task force. ArticleCASPubMedPubMed Central Google Scholar
Zhang, W., Jones, A. & Doherty, M. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann. Rheum. Dis.63, 901–907 (2004). ArticleCASPubMedPubMed Central Google Scholar
Neame, R., Zhang, W. & Doherty, M. A historic issue of the Annals: three papers examine paracetamol in osteoarthritis. Ann. Rheum. Dis.63, 897–900 (2004). ArticleCASPubMedPubMed Central Google Scholar
Lee, C., Straus, W. L., Balshaw, R., Barlas, S., Vogel, S. & Schnitzer, T. J. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum.51, 746–754 (2004). ArticleCASPubMed Google Scholar
Vane, J. R., Bakhle, Y. S. & Botting, R. M. Cyclooxygenases 1 and 2. Ann. Rev. Pharmacol. Toxicol.38, 97–120 (1998). ArticleCAS Google Scholar
Samad, T. A. et al. Interleukin-1β-mediated induction of COX-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature410, 471–475 (2001). ArticleCASPubMed Google Scholar
Watson, M. C., Brookes, S. T., Kirwan, J. R. & Faulkner, A. in The Cochrane Library, Issue 1 10.1002/14651858.CD000142 (Update Software Ltd, Oxford, 2003). Google Scholar
Warner, T. D. 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. USA96, 7563–7568 (1999). ArticleCASPubMed Google Scholar
Bensen, W. G. et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin. Proc.74, 1095–1105 (1999). ArticleCASPubMed Google Scholar
Day, R. et al. A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/Ibuprofen Comparator Study Group. Arch. Intern. Med.160, 1781–1787 (2000). ArticleCASPubMed Google Scholar
McAlindon, T. E., LaValley, M. P., Gulin, J. P. & Felson, D. T. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA283, 1469–1475 (2000). ArticleCASPubMed Google Scholar
Zerkak, D. & Dougados, M. The use of glucosamine therapy in osteoarthritis. Curr. Pain Headache Rep.8, 507–511 (2004). ArticlePubMed Google Scholar
Chard, J & Dieppe, P. Glucosamine for osteoarthritis: magic, hype, or confusion? It's probably safe — but there's no good evidence that it works. BMJ322, 1439–1440 (2001). This paper questions the validity of glucosamine as a treatment for OA. ArticleCASPubMedPubMed Central Google Scholar
Biggee, B. A. & McAlindon, T. Glucosamine for osteoarthritis: part I, review of the clinical evidence. Med. Health RI87, 176–179 (2004). Google Scholar
Lin, J., Zhang, W., Jones, A. & Doherty, M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta–analysis of randomised controlled trials. BMJ329, 324 (2004). ArticleCASPubMedPubMed Central Google Scholar
Mason, L., Moore, R. A., Edwards, J. E., Derry, S. & McQuay, H. J. Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis. BMC Musculoskelet. Disord.5, 28 (2004). ArticlePubMedPubMed CentralCAS Google Scholar
Ayral, X. Injections in the treatment of osteoarthritis. Best Pract. Res. Clin. Rheumatol.15, 609–626 (2001). ArticleCASPubMed Google Scholar
Gossec, L. & Dougados, M. Intra-articular treatments in osteoarthritis: from the symptomatic to the structure modifying. Ann. Rheum. Dis.63, 478–482 (2004). ArticleCASPubMedPubMed Central Google Scholar
Creamer, P. Intra-articular corticosteroid treatment in osteoarthritis. Curr. Opin. Rheumatol.11, 417–421 (1999). ArticleCASPubMed Google Scholar
Lohmander, L. S. et al. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group. Ann. Rheum. Dis.55, 424–431 (1996). ArticleCASPubMedPubMed Central Google Scholar
Brandt, K. D., Smith, G. N. Jr & Simon, L. S. Intraarticular injection of hyaluronan as treatment for knee osteoarthritis: what is the evidence? Arthritis Rheum.43, 1192–1203 (2000). ArticleCASPubMed Google Scholar
Lo, G. H., LaValley, M., McAlindon, T. & Felson, D. T. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA.290, 3115–3221 (2003). ArticleCASPubMed Google Scholar
Haringman, J. J., Ludikhuize, J. & Tak, P. P. Chemokines in joint disease: the key to inflammation? Ann. Rheum. Dis.63, 1186–1194 (2004). ArticleCASPubMedPubMed Central Google Scholar
Fan, Z. et al. Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1. Clin. Exp. Rheumatol.22, 103–106 (2004). CASPubMed Google Scholar
Sandell, L. J. & Aigner, T. Articular cartilage and changes in osteoarthritis. An introduction: cell biology of osteoarthritis. Arthritis Res.3, 107–113 (2001). ArticleCASPubMedPubMed Central Google Scholar
Matsumoto, T., Gargosky, S. E., Iwasaki, K. & Rosenfeld, R. G. Identification and characterization of insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP proteases in human synovial fluid. J. Clin. Endocrinol. Metab.81, 150–155 (1996). CASPubMed Google Scholar
Lajeunesse, D. The role of bone in the treatment of osteoarthritis. Osteoarthr. Cartil.12, S34–S38 (2004). ArticlePubMed Google Scholar
Dumond, H. et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum.48, 3118–3129 (2003). A recent perspective of leptin playing an important role in OA. ArticleCASPubMed Google Scholar
Figenschau, Y. et al. Human articular chondrocytes express functional leptin receptors. Biochem. Biophys. Res. Commun.287, 190–197 (2001). ArticleCASPubMed Google Scholar
Lohmander, L. S., Atley, L. M., Pietka, T. A. & Eyre, D. R. The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum.48, 3130–3139 (2003). ArticleCASPubMed Google Scholar
Rudolphi, K. et al. Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthr. Cartil.11, 738–746 (2003). ArticleCASPubMed Google Scholar
Zhang, X., Mao, Z. & Yu, Ch. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J. Orthop. Res.22, 742–750 (2004). ArticleCASPubMed Google Scholar
Fuchs, S. et al. Differential induction and regulation of matrix metalloproteinases in osteoarthritic tissue and fluid synovial fibroblasts. Osteoarthr. Cartil.12, 409–418 (2004). ArticleCASPubMed Google Scholar
Kevorkian, L. et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum.50, 131–141 (2004). ArticleCASPubMed Google Scholar
Francois, M. et al. Peroxisome proliferator-activated receptor-γ down regulates chondrocyte matrix meatlloproteinase-1 via a novel composite element. J. Biol. Chem.279, 28411–28418 (2004). ArticleCASPubMed Google Scholar
Bordji, K. et al. Evidence for the presence of peroxisome proliferator-activated receptor (PPAR)α and γ and retinoid Z receptor cartilage. J. Biol. Chem.275, 12243–12250 (2000). ArticleCASPubMed Google Scholar
Martel-Pelletier, M., Pelletier, J. P. & Fahni, H. Cyclooxygenase-2 and prostaglandins in articular tissues. Semin. Arthritis Rheum.33, 155–167 (2003). ArticleCASPubMed Google Scholar
Fahmi, H., Pelletier, J. P., Mineau, F. & Martel-Pelletier, J. 15d-PGJ2 is acting as “dual agent” on the regulation of COX-2 expression in human osteoarthritic chondrocytes. Osteoarthr. Cartil.10, 845–848 (2002). ArticleCASPubMed Google Scholar
Aupperle, K. R. et al. NF-κB regulation by I kappa B kinase in primary fibroblast-like synoviocytes. J. Immunol.163, 427–433 (1999). CASPubMed Google Scholar
Aupperle, K. R. et al. Expression and regulation of inducible IκB kinase (IKK-i) in human fibroblast-like synoviocytes. Cell. Immunol.214, 54–59 (2001). ArticleCASPubMed Google Scholar
Tegeder, I. et al. Specific inhibition of IκB kinase reduces hyperalgesia in inflammatory and neuropathic pain models. J. Neurosci.24, 1673–1645 (2004). ArticleCAS Google Scholar
Jobin, C. et al. Specific NF-κB blockade selectively inhibits tumour necrosis factor α-induced COX2 but not constitutive Cox-1 gene expression in HT29 cells. Immunology95, 537–543 (1998). ArticleCASPubMedPubMed Central Google Scholar
Pelletier, J. -P. Rationale for the use of structure-modifying drugs and agents in the treatment of osteoarthritis. Osteoarthr. Cartil.12 (Suppl. A), 63–68 (2003). Google Scholar
Buckland-Wright, C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthr. Cartil.12, (Suppl. A) 10–19 (2004). Article Google Scholar
Felson, D. T. & Neogi, T. Osteoarthritis: is it a disease of cartilage or bone? Arthritis Rheum.50, 341–344 (2004). A recent paper discussing the contribution of both cartilage and bone to the progression of the disease. ArticlePubMed Google Scholar
Grynpas, M. D., Alpert, B., Katz, I., Lieberman, I. & Pritzker, K. P. Subchondral bone in osteoarthritis. Calcif. Tissue Int.49, 20–26 (1991). ArticleCASPubMed Google Scholar
Hayami, T. et al. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. Arthritis Rheum.50, 1193–1206 (2004). ArticleCASPubMed Google Scholar
Doschak, M. R., Wohl, G. R., Hanley, D. A., Bray, R. C. & Zernicke, R. F. Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee. J. Orthop. Res.22, 942–948 (2004). ArticleCASPubMed Google Scholar
Myers, S. L., Brandt, K. D., Burr, D. B., O'Connor, B. L. & Albrecht, M. Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis. J. Rheumatol.26, 2645–2653 (1999). CASPubMed Google Scholar
Bingham, C. et al. Clinically significant placebo improvement occurs by 6 months and is maintained through 24 months in a study of knee OA pain and function. Osteoarthr. Cartil.12, S132 Abs. P323 (2004). Google Scholar
Menkes, C. J. & Lane, N. E. Are osteophytes good or bad? Osteoarthr. Cartil.12, S53–S54 (2004). ArticlePubMed Google Scholar
Uchino, M. et al. Growth factor expression in the osteophytes of the human femoral head in osteoarthritis. Clin. Orthop.377, 119–125 (2000). Article Google Scholar
Brandt, K. D. Osteophytes in osteoarthritis. Clinical aspects. Osteoarthr. Cartil.7, 334–335 (1999). ArticleCASPubMed Google Scholar
Van Osch, G. J., Van der Kraan, P. M., Van Valburg, A. A. & Van den Berg, W. B. The relation between cartilage damage and osteophyte size in a murine model for osteoarthritis in the knee. Rheumatol. Int.16, 115–119 (1996). ArticleCASPubMed Google Scholar
Lanyon, P., O'Reilly, S., Jones, A. & Doherty, M. Radiographic assessment of symptomatic knee osteoarthritis in the community: definitions and normal joint space. Ann. Rheum. Dis.57, 595–601 (1998). ArticleCASPubMedPubMed Central Google Scholar
Ghosh, P. Vascular mechanisms in osteoarthritis. Best Practice Res. Clin. Rheumatol.15, 693–710 (2001). ArticleCAS Google Scholar
Simkin, P. A. in Osteoarthritic Joint Pain (Novartis Foundation Symposium) 179–190 (Wiley, Chichester, 2004). Google Scholar
Takeda, S. et al. Leptin regulates bone formation via the sympathetic nervous system. Cell111, 305–317 (2002). ArticleCASPubMed Google Scholar
Ducy, P. et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell100, 197–207 (2000). ArticleCASPubMed Google Scholar
Dean, G., Hoyland, J. A., Denton, J., Donn, R. P. & Freemont, A. J. Mast cells in the synovium and synovial fluid in osteoarthritis. Br. J. Rheumatol.32, 671–675 (1993). ArticleCASPubMed Google Scholar
Lindblad, S. & Hedfors, E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheumatol.30, 1081–1088 (1987). ArticleCAS Google Scholar
Halverson, P. B. & Derfus, B. A. Calcium crystal-induced inflammation. Curr Opin. Rheumatol.13, 221–224 (2001). ArticleCASPubMed Google Scholar
Kato, T., Xiang, Y., Nakamura, H. & Nishioka, K. Neoantigens in osteoarthritic cartilage. Curr. Opin. Rheumatol.16, 604–608 (2004). ArticleCASPubMed Google Scholar
Abramson, S. B. Inflammation in osteoarthritis. J. Rheumatol. Suppl.70, 70–76 (2004). CASPubMed Google Scholar
Poole, A. R. Biochemical/immunochemical biomarkers of osteoarthritis: utility for prediction of incident or progressive osteoarthritis. Rheum. Dis. Clin. North Am.29, 803–818 (2003). This paper provides a classic review on biomarkers in OA. ArticlePubMed Google Scholar
Opree, A. & Kress, M. Involvement of the proinflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J. Neurosci.20, 6289–6293 (2000). ArticleCASPubMed Google Scholar
Safieh-Garabedian, B., Poole, S., Allchorne, A., Winter, J. & Woolf, C. J. Contribution of interleukin-1β to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Br. J. Pharmacol.115, 1265–1275 (1995). ArticleCASPubMedPubMed Central Google Scholar
Woolf, C. J., Allchorne, A., Safieh-Garabedian, B. & Poole, S. Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor α. Br. J. Pharmacol.121, 417–424 (1997). ArticleCASPubMedPubMed Central Google Scholar
Chen, X., Tanner, K. & Levine, J. D. Mechanical sensitization of cutaneous C-fiber nociceptors by prostaglandin E2 in the rat. Neurosci. Lett.267, 105–108 (1999). ArticleCASPubMed Google Scholar
Manning, D. C., Raja, S. N., Meyer, R. A. & Campbell, J. N. Pain and hyperalgesia after intradermal injection of bradykinin in humans. Clin. Pharmacol. Ther.50, 721–729 (1991). ArticleCASPubMed Google Scholar
Mizumura, K. Natural history of nociceptor sensitization — the search for peripheral mechanism of hyperalgesia. Pain Rev.5, 59–82 (1998). ArticleCAS Google Scholar
Flechtenmacher, J. et al. Bradykinin-receptor-inhibition — a therapeutic option in osteoarthritis? Osteoarthr. Cartil.12, S137 Abs. P332 (2004). Google Scholar
Saito, T. & Koshino, T. Distribution of neuropeptides in synovium of the knee with osteoarthritis. Clin. Orthop.376, 172–182 (2000). Article Google Scholar
Vilensky, J. A. & Cook, J. A. Neurogenic acceleration of osteoarthritis. Curr. Opin. Rheumatol.10, 251–255 (1998). ArticleCASPubMed Google Scholar
Hurley, M. V., Scott, D. L., Rees, J. & Newham, D. J. Sensorimotor changes and functional performance in patients with knee osteoarthritis. Ann. Rheum. Dis.56, 641–648 (1997). ArticleCASPubMedPubMed Central Google Scholar
Baker, K. & McAlindon, T. Exercise for knee osteoarthritis. Curr. Opin. Rheumatol.12, 456–463 (2000). ArticleCASPubMed Google Scholar
Slemenda, C. et al. Quadriceps weakness and osteoarthritis of the knee. Ann. Int. Med.127, 97–104 (1997). ArticleCASPubMed Google Scholar
Becker, R., Berth, A., Nehring, M. & Awiszus, F. Neuromuscular quadriceps dysfunction prior to osteoarthritis of the knee. J. Orthop. Res.22, 768–773 (2004). ArticlePubMed Google Scholar
O'Connor, B. L. & Vilensky, J. A. Peripheral and central nervous system mechanisms of joint protection. Am. J. Orthop.32, 330–336 (2003). PubMed Google Scholar
Sharma, L., Dunlop, D. D., Cahue, S., Song, J. & Hayes, K. W. Quadriceps strength and osteoarthritis progression in malaligned and lax knees. Ann. Intern. Med.138, 613–619 (2003). ArticlePubMed Google Scholar
Creamer, P., Hunt, M. & Dieppe, P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J. Rheumatol.23, 1031–1036 (1996). CASPubMed Google Scholar
Schaible, H. G., Ebersberger, A., Von Banchet, G. S. Mechanisms of pain in arthritis. Ann. NY Acad. Sci.966, 343–354 (2002). ArticleCASPubMed Google Scholar
Butcher, E. C., Berg, E. L. & Kunkel, E. J. Systems biology in drug discovery. Nature Biotechnology22, 1253–1259 (2004). ArticleCASPubMed Google Scholar
Bonnet, C. S. & Walsh, D. A. Osteoarthritis, angiogenesis and inflammation. Rheumatology (Oxford)44, 7–16 (2005). An interesting recent review illustrating the relevance of angiogenic processes to the pathophysiology of OA. ArticleCAS Google Scholar
Walsh, D. A. Angiogenesis in osteoarthritis and spondylosis: successful repair with undesirable outcomes. Curr. Opin. Rheumatol.16, 609–615 (2004). ArticlePubMed Google Scholar
Balint, G. & Szebenyi, B. Hereditary disorders mimicking and/or causing premature osteoarthritis. Baillieres Best. Pract. Res. Clin. Rheumatol.14, 219–250 (2000). ArticleCASPubMed Google Scholar
Dequeker, J., Boonen, N., Aerssens, J. & Westhovens, R. Inverse relationship osteoarthritis — osteoporosis: what is the evidence? What are the consequences? Br. J. Rheumatol.35, 813–820 (1996). ArticleCASPubMed Google Scholar
Lark, M. W. & Blake, S. M. Development of novel therapeutics to treat joint diseases — what can be learned from other diseases? Curr. Opin. Pharmacol.4, 273–275 (2004). ArticleCAS Google Scholar
Aspden, R. M., Scheven, B. A. A. & Hutchison, J. D. Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet357, 1118–1120 (2001). One of the first publications suggesting a direct relationship between OA and metabolic disorders. ArticleCASPubMed Google Scholar
Toda, Y. et al. Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after weight control program. J. Rheumatol.25, 2181–2186 (1998). CASPubMed Google Scholar
Loeser, R. F. Systemic and local regulation of articular cartilage metabolism: where does leptin fit in the puzzle? Arthritis Rheum.48, 3009–3012 (2003) ArticleCASPubMed Google Scholar
Yagami, K. et al. A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes. Bone34, 648–655 (2004). ArticleCASPubMed Google Scholar
Henroitin, Y., Sanchez, C. & Reginster, J. Y. The inhibition of metalloproteinases to treat osteoarthritis: reality and new perspectives. Expert Opin. Ther. Patents12, 29–43 (2002). Article Google Scholar
Skiles, J. W., Gonella, N. C. & Jeng, A. Y. The design, structure and clinical update of small metalloproteinase inhibitors. Curr. Med. Chem.11, 2911–2977 (2004). ArticleCASPubMed Google Scholar
Schnitzer, T. J. et al. TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet.364, 665–674 (2004). ArticleCASPubMed Google Scholar
Brune, K. Safety of anti-inflammatory treatment — new ways of thinking. Rheumatology (Oxford).43 S16–S20 (2004). ArticleCAS Google Scholar
Wallace, J. L. & Del Soldato, P. The therapeutic potential of NO-NSAIDs. Fundam. Clin. Pharmacol.17, 11–20 (2003). ArticleCASPubMed Google Scholar
Whittle, B. J. Cyclooxygenase and nitric oxide systems in the gut as therapeutic targets for safer anti-inflammatory drugs. Curr. Opin. Pharmacol.4, 538–545 (2004). ArticleCASPubMed Google Scholar
Garnero, P. et al. Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis. Arthritis Rheum.46, 2613–2624 (2002). ArticleCASPubMed Google Scholar
Cerejo, R. et al. The association between cartilage activity measured in serum and progression of knee osteoarthritis in patients with and without evidence of generalized disease. Arthritis Rheum.46, S144 (2002). Article Google Scholar
Sharif, M. et al. Suggestion of nonlinear or phasic progression of knee osteoarthritis based on measurements of serum cartilage oligomeric matrix protein levels over five years. Arthritis Rheum.50, 2479–2488 (2004). ArticleCASPubMed Google Scholar
Kola, I. & Landis, J. Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Discovery3, 711–715 (2004). ArticleCAS Google Scholar