328 Lack of Disease Modifying Activity of Celecoxib in End-Stage Osteoarthritis: A Randomized Controlled Trial

Boer, T.N. de; Mastbergen, S.C.; Huisman, André; Polak, A.A.; Bijlsma, J. W. J.; Lafeber, F.P.

doi:10.1016/s1063-4584(10)60355-x

Cited by 3 publications

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“…The present results support the findings of previous preclinical and clinical studies showing the lack of a chondroprotective effect of celecoxib (7, 8). However, we cannot completely rule out the possibility of a direct protective effect of COX‐2 inhibition on joint cartilage, because a beneficial effect might possibly have been counteracted by increased loading of the affected joint due to the drug's antiinflammatory or analgesic effects, with associated progression of OA.…”

Section: Discussionsupporting

confidence: 93%

“…Likewise, previous in vitro and ex vivo studies have shown that celecoxib, a representative selective COX‐2 inhibitor, has chondroprotective effects in cultures of chondrocytes and cartilage (5, 6). However, in vivo evaluation by the same group failed to demonstrate a beneficial effect of celecoxib in the canine model of OA (7), and a recent randomized controlled trial in OA patients, also conducted by that group, similarly failed to replicate the chondroprotective effect of celecoxib (8).…”

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confidence: 99%

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Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice

Fukai¹,

Kamekura²,

Chikazu³

et al. 2011

Arthritis & Rheumatism

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Objective. To investigate the chondroprotective effect of cyclooxygenase 2 (COX-2) inhibition in experimental osteoarthritis (OA).Methods. The expression of prostaglandin E 2 synthetic enzymes was examined by immunostaining of tibial cartilage from mice with surgically induced knee joint instability and from OA patients undergoing total knee arthroplasty. The effect of orally administered celecoxib (10 mg/kg/day and 30 mg/kg/day) or vehicle alone in mice was examined 12 weeks after the induction of OA. To investigate the involvement of COX-1 and COX-2 in OA development, we also created the model in COX-1-homozygous-knockout (Ptgs1 ؊/؊ ) mice and COX-2-homozygous-knockout (Ptgs2 ؊/؊ ) mice. OA severity was assessed using a grading system developed by our group and by the Osteoarthritis Research Society International scoring system.Results. In mouse and human OA cartilage, the expression of the inducible enzymes COX-2 and microsomal prostaglandin E synthase 1 (mPGES-1) was enhanced, while that of the constitutive enzymes COX-1, cytosolic PGES, and mPGES-2 was suppressed. Daily celecoxib treatment did not prevent cartilage degradation or osteophyte formation during OA development in the mouse model. Furthermore, neither Ptgs1 ؊/؊ mice nor Ptgs2 ؊/؊ mice exhibited any significant difference in OA development as compared to wild-type littermates.Conclusion. The two COX enzymes differ in terms of regulation of their expression during OA development. Nevertheless, experiments using inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect of COX-2 inhibition in the mouse surgical OA model.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice

Fukai¹,

Kamekura²,

Chikazu³

et al. 2011

Arthritis & Rheumatism

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“…Patients at the Sint Franciscus Gasthuis in Rotterdam, The Netherlands, with severe knee OA who were eligible for TKR surgery, were included. At time of TKR surgery, blood, cartilage tissue, and synovial tissue were collected 36 . Cartilage and synovial tissue were kept in phosphate buffered saline for a maximum of 4 h during transport to the University Medical Centre Utrecht where tissues were further processed under laminar flow conditions.…”

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confidence: 99%

Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage

Boer

Spil

Huisman

et al. 2012

Osteoarthritis and Cartilage

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165

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COX-2-Selective NSAIDs and Risk of Hip or Knee Replacements: A Population-Based Case–Control Study

et al. 2012

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Disease models of osteoarthritis (OA) have shown that COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs, coxibs) may have beneficial effects on cartilage. Clinical or epidemiological evidence for this potential association is scarce. The objective of this study was to evaluate the risk of hip or knee replacement in users of coxibs compared to nonselective NSAIDs. A population-based case-control study was conducted with the Dutch PHARMO Record Linkage System. Cases (n = 26,202) had a first replacement of the hip or knee after enrollment (2000-2009). Up to two controls (without hip or knee replacement) were matched by year of birth, gender, healthcare region, and calendar year. Using conditional logistic regression analysis, odds ratios (ORs) for hip or knee replacement were estimated by comparing long-term (≥1 year) nonselective NSAID use with long-term coxib use. Analyses were statistically adjusted for disease and drug history. Long-term use of nonselective NSAIDs was not associated with a different risk of hip replacement (adjusted OR = 0.89, 95 % CI 0.65-1.22) or knee replacement (adjusted OR = 0.74, 95 % CI 0.49-1.11) as compared to long-term coxib use. Results were not different after stratification by gender, age, and cardiovascular or gastrointestinal disease. This study shows that long-term users of nonselective NSAIDs do not have a different risk of hip or knee replacement as compared to long-term coxib users. Therefore, our results do not support that patients with OA could benefit from using coxibs in order to slow progression of this disease.

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328 Lack of Disease Modifying Activity of Celecoxib in End-Stage Osteoarthritis: A Randomized Controlled Trial

Cited by 3 publications

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Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice

Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice

Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage

COX-2-Selective NSAIDs and Risk of Hip or Knee Replacements: A Population-Based Case–Control Study

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