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See detailOsteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study
Bruyère, Olivier ULg; Collette, Julien ULg; Kothari, M. et al

in Annals of the Rheumatic Diseases (2006), 65(8), 1050-1054

Objective: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. Methods: 62 patients of both sexes ... [more ▼]

Objective: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. Methods: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging ( MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score ( WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers ( serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 ( YKL-40), cartilage oligomeric matrix protein ( COMP), and C-telopeptide of type I collagen ( CTX-I), and urine C-telopeptide of type II collagen ( CTX-II)) were measured at baseline and after three months. Results: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 ( 0.08) mm of their medial thickness, compared with a mean increase of 0.05 ( 0.19) mm for patients in the lowest quartile ( p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS ( p = 0.004). Conclusions: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis. [less ▲]

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See detailInfluence of baseline patient characteristics on response to one-monthly and daily oral ibandronate therapy: 2-year findings from MOBILE
Reginster, Jean-Yves ULg; Hawker, G.; Bolognese, M. et al

in Annals of the Rheumatic Diseases (2006, June), 65(Suppl.II), 426

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See detailUpper gastrointestinal safety and tolerability profile of once-monthly and daily oral ibandronate: mobile 2-year analysis
Czerwinski, E.; Nuti, R.; Greenwald, M. et al

in Annals of the Rheumatic Diseases (2006, June), 65(Suppl.II), 415

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See detailEfficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study
Reginster, Jean-Yves ULg; Adami, S.; Lakatos, P. et al

in Annals of the Rheumatic Diseases (2006), 65(5), 654-661

BACKGROUND: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been ... [more ▼]

BACKGROUND: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been developed to overcome this problem. OBJECTIVE: To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis. METHODS: MOBILE, a randomised, phase III, non-inferiority study, compared the efficacy and safety of once-monthly ibandronate with daily ibandronate, which has previously been shown to reduce vertebral fracture risk in comparison with placebo. RESULTS: 1609 postmenopausal women were randomised. Substantial increases in lumbar spine bone mineral density (BMD) were seen in all treatment arms: 5.0%, 5.3%, 5.6%, and 6.6% in the daily and once-monthly groups (50 + 50 mg, 100 mg, and 150 mg), respectively. It was confirmed that all once-monthly regimens were at least as effective as daily treatment, and in addition, 150 mg was found to be better (p<0.001). Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen; 150 mg produced the most pronounced effect (p<0.05 versus daily treatment). Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after 3 months, were maintained throughout. The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens. Ibandronate was well tolerated, with a similar incidence of adverse events across groups. CONCLUSIONS: Once-monthly oral ibandronate is at least as effective and well tolerated as daily treatment. Once-monthly administration may be more convenient for patients and improve therapeutic adherence, thereby optimising outcomes. [less ▲]

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See detailBone-derived mediators and cartilage degradation
Henrotin, Yves ULg

in Annals of the Rheumatic Diseases (2006), 65(Suppl 11), 0022

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See detailBone-derived mediators and cartilage degradation
Henrotin, Yves ULg

in Annals of the Rheumatic Diseases (2006)

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See detailBone-derived mediators and cartilage degradation
Henrotin, Yves ULg

in Annals of the Rheumatic Diseases (2006), 65(Suppl 11), 0022

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See detailEULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis
D'Agostino, M. A.; Conaghan, P.; Le Bars, M. et al

in Annals of the Rheumatic Diseases (2005), 64(12), 1703-1709

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to ... [more ▼]

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity >= 30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness >= 4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth >= 4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade >= 3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare'', such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare''. [less ▲]

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See detailThree year joint space narrowing predicts long term incidence of knee surgery in patients with osteoarthritis: an eight year prospective follow up study
Bruyère, Olivier ULg; Richy, F.; Reginster, Jean-Yves ULg

in Annals of the Rheumatic Diseases (2005), 64(12), 1727-1730

OBJECTIVE: To assess the clinical relevance of mean and minimum femorotibial joint space narrowing (JSN) for predicting future osteoarthritis related surgery in patients with knee osteoarthritis. METHODS ... [more ▼]

OBJECTIVE: To assess the clinical relevance of mean and minimum femorotibial joint space narrowing (JSN) for predicting future osteoarthritis related surgery in patients with knee osteoarthritis. METHODS: 126 subjects with primary knee osteoarthritis were followed prospectively for a mean eight years. Minimum and mean joint space width (JSW) were assessed from standard x rays at baseline and after a follow up of three years. The rate of knee osteoarthritis related surgery was recorded for the following five years. RESULTS: After a mean follow up of eight years, 16 patients (12.7%) had received osteoarthritis related joint surgery. The areas under the curves (AUC) resulting from the receiver operating characteristic curve analyses for predicting osteoarthritis surgery were 0.73 (p=0.006) for minimum JSN and 0.55 (p=0.54) for mean JSN. The cut off for minimum JSN maximising sensitivity and specificity for predicting future surgery was a change of 0.7 mm or more in minimum joint space width over a period of three years. However, no meaningful differences were observed for cut off values between 0.5 and 0.8 mm The relative risk (adjusted for age, body mass index, baseline symptoms, and baseline JSW) of experiencing osteoarthritis related surgery during the eight year of follow up was 5.15 (95% confidence interval, 1.70 to 15.60) (p=0.004) in patients with a minimum joint space narrowing of 0.7 mm or more during the first three years of the study. CONCLUSIONS: A cut off of 0.5 to 0.8 mm in minimum JSN, measured on standard x rays, reflects a clinically relevant progression in patients with knee osteoarthritis. [less ▲]

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See detailIntravenous ibandronate injections are at least as effective as daily oral ibandronate: consistent effect across subgroups
Reginster, Jean-Yves ULg; Stepan, J. J.; Halse, J. et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 365

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See detailOnce-monthly and daily oral ibandronate are at least as effective in improving proximal femur BMD in postmenopausal osteoporosis: 12-month data from MOBILE
Reginster, Jean-Yves ULg; Lorenc, R.; Stepan, J. J. et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 93

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See detailStrontium ranelate reduces the risk of vertebral fractures in osteoporotic postmenopausal women whatever the baseline vertebral fractures status
Roux, Christian; Fardellone, P.; Fechtenbaum, Jacques et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 359

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See detailGlobal prevalence and skeletal implications of vitamin D inadequacy
Reginster, Jean-Yves ULg; Richy, Florent; Rabenda, Véronique ULg et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 362

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See detailReduction in the risk of back pain persists at least 30 months after discontinuation of teriparatide treatment: a meta-analysis
Reginster, Jean-Yves ULg; Nevitt, M. C.; Chen, P. et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 521

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See detailUpper gastrointestinal safety and tolerability profile of once-monthly and daily oral ibandronate is similar in postmenopausal osteoporosis: 1-year results from MOBILE
Adami, Silvio; Tanko, L. B.; Nuti, R. et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 364

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See detailTwo-year efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: the MOBILE study
Cooper, C.; Delmas, P. D.; Felsenberg, D. et al

in Annals of the Rheumatic Diseases (2005, June), 64(Suppl.III), 68

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See detailA naturalistic study of the determinants of health related quality of life improvement in osteoarthritic patients treated with non-specific non-steroidal antiinflammatory drugs
Rabenda, Véronique ULg; Burlet, N.; Ethgen, Olivier ULg et al

in Annals of the Rheumatic Diseases (2005), 64(5), 688-693

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify ... [more ▼]

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes. METHODS: A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up. RESULTS: All QoL dimensions were significantly (p<0.01) decreased in patients with OA compared with controls. Significant improvement (p<0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA. CONCLUSION: OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs. [less ▲]

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See detailEULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 2: exploring decision rules for clinical utility
Conaghan, P.; D'Agostino, M. A.; Ravaud, P. et al

in Annals of the Rheumatic Diseases (2005), 64(12), 1710-1714

BACKGROUND: Synovial inflammation (as defined by hypertrophy and effusion) is common in osteoarthritis (OA) and may be important in both pain and structural progression. OBJECTIVE: To determine if ... [more ▼]

BACKGROUND: Synovial inflammation (as defined by hypertrophy and effusion) is common in osteoarthritis (OA) and may be important in both pain and structural progression. OBJECTIVE: To determine if decision rules can be devised from clinical findings and ultrasonography (US) to allow recognition of synovial inflammation in patients with painful knee OA. METHODS: A EULAR-ESCISIT cross sectional, multicentre study enrolled subjects with painful OA knee who had clinical, radiographic, and US evaluations. A classification and regression tree (CART) analysis was performed to find combinations of predictor variables that would provide high sensitivity and specificity for clinically detecting synovitis and effusion in individual subjects. A range of definitions for the two key US variables, synovitis and effusion (using different combinations of synovial thickness, depth, and appearance), were also included in exploratory analyses. RESULTS: 600 patients with knee OA were included in the analysis. For both knee synovitis and joint effusion, the sensitivity and specificity were poor, yielding unsatisfactory likelihood ratios (75% sensitivity, 45% specificity, and positive LR of 1.36 for knee synovitis; 71.6% sensitivity, 43.2% specificity, and positive LR of 1.26 for joint effusion). The exploratory analyses did not improve the sensitivity and specificity (demonstrating positive LRs of between 1.26 and 1.57). CONCLUSION: Although it is possible to determine clinical and radiological predictors of OA inflammation in populations, CART analysis could not be used to devise useful clinical decision rules for an individual subject. Thus sensitive imaging techniques such as US remain the most useful tool for demonstrating synovial inflammation of the knee at the individual level. [less ▲]

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See detailLumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib
Tannenbaum, H.; Berenbaum, F.; Reginster, Jean-Yves ULg et al

in Annals of the Rheumatic Diseases (2004), 63(11), 1419-1426

Objectives: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis (OA) in a 13 week, multicentre, randomised, double blind study. Methods: After a 327 day washout ... [more ▼]

Objectives: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis (OA) in a 13 week, multicentre, randomised, double blind study. Methods: After a 327 day washout period for non-steroidal anti-inflammatory drugs, 1702 patients with knee OA were randomised to lumiracoxib 200 or 400 mg once daily (od), celecoxib 200 mg od, or placebo (2:2:2:1). A visual analogue scale (VAS) pain intensity greater than or equal to40 mm was required. Primary efficacy variables were OA pain intensity (VAS mm) in the target knee, patient's global assessment of disease activity (VAS mm), and WOMAC pain subscale and total scores at 13 weeks. OA pain intensity, patient's and physician's global assessment of disease activity, and WOMAC (total and all subscale scores) were analysed by visit as secondary variables. Results: Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo. Lumiracoxib 200 mg od and celecoxib 200 mg od achieved similar improvements in OA pain intensity and functional status. Lumiracoxib 400 mg od demonstrated better efficacy for OA pain intensity and patient's global assessment of disease activity at weeks 2, 4, and 8 and similar efficacy at week 13 compared with celecoxib 200 mg od. The incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs was similar in each group. Conclusion: Lumiracoxib demonstrated significant improvement in OA pain intensity, patient's global assessment of disease activity, and the WOMAC pain subscale and total scores compared with placebo. Lumiracoxib was well tolerated in this study, with overall tolerability similar to that of placebo and celecoxib. [less ▲]

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See detailTime dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach
Richy, F.; Bruyère, Olivier ULg; Ethgen, Olivier ULg et al

in Annals of the Rheumatic Diseases (2004), 63(7), 759-766

OBJECTIVES: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. METHODS: An ... [more ▼]

OBJECTIVES: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. METHODS: An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories. RESULTS: Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies. CONCLUSION: This meta-analysis characterised the "compound" and "time" aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment. [less ▲]

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