Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
Identifieur interne : 005198 ( PascalFrancis/Curation ); précédent : 005197; suivant : 005199Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial
Auteurs : Jean-Yves Reginster [Belgique] ; Janusz Badurski [Pologne] ; Nicholas Bellamy [Australie] ; William Bensen [Canada] ; Roland Chapurlat [France] ; Xavier Chevalier [France] ; Claus Christiansen [Danemark] ; Harry Genant [États-Unis] ; Federico Navarro [Espagne] ; Evgeny Nasonov [Russie] ; Philip N. Sambrook [Australie] ; Timothy D. Spector [Royaume-Uni] ; Cyrus Cooper [Royaume-Uni]Source :
- Annals of the rheumatic diseases [ 0003-4967 ] ; 2013.
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- Pascal (Inist)
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Abstract
Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee Osteoarthrltis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p=0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p=0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p=0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.
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Sambrook</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Institute of Bone and Joint Research, Royal North Shore Hospital</s1><s2>St Leonards, NSW</s2><s3>AUS</s3><sZ>11 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D." last="Spector">Timothy D. Spector</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas' Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>MRC Lifecourse Epidemiology Unit, NIHR Musculoskeletal Biomedical Research Unit, University of Southampton, University of Oxford</s1><s2>Oxford</s2><s3>GBR</s3><sZ>13 aut.</sZ></inist:fA14><country>Royaume-Uni</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">13-0074409</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 13-0074409 INIST</idno><idno type="RBID">Pascal:13-0074409</idno><idno type="wicri:Area/PascalFrancis/Corpus">000C66</idno><idno type="wicri:Area/PascalFrancis/Curation">005198</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial</title><author><name sortKey="Reginster, Jean Yves" sort="Reginster, Jean Yves" uniqKey="Reginster J" first="Jean-Yves" last="Reginster">Jean-Yves Reginster</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Public Health Epidemiology and Health Economics, University of Liege</s1><s2>Liege</s2><s3>BEL</s3><sZ>1 aut.</sZ></inist:fA14><country>Belgique</country></affiliation></author><author><name sortKey="Badurski, Janusz" sort="Badurski, Janusz" uniqKey="Badurski J" first="Janusz" last="Badurski">Janusz Badurski</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Centre of Osteoporosis and Osteoarticular Diseases</s1><s2>Bialystok</s2><s3>POL</s3><sZ>2 aut.</sZ></inist:fA14><country>Pologne</country></affiliation></author><author><name sortKey="Bellamy, Nicholas" sort="Bellamy, Nicholas" uniqKey="Bellamy N" first="Nicholas" last="Bellamy">Nicholas Bellamy</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Centre of National Research on Disability (CONROD), University of Queensland, Herston</s1><s2>Queensland</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Bensen, William" sort="Bensen, William" uniqKey="Bensen W" first="William" last="Bensen">William Bensen</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>DeGroot School of Medicine, McMaster University Hamilton</s1><s2>Hamilton, Ontario</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Chapurlat, Roland" sort="Chapurlat, Roland" uniqKey="Chapurlat R" first="Roland" last="Chapurlat">Roland Chapurlat</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>INSERM UMR 1033, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Universite de Lyon</s1><s2>Lyon</s2><s3>FRA</s3><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Chevalier, Xavier" sort="Chevalier, Xavier" uniqKey="Chevalier X" first="Xavier" last="Chevalier">Xavier Chevalier</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Service de Rhumatologie, Hôpital Henri Mondor</s1><s2>Créteil</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Christiansen, Claus" sort="Christiansen, Claus" uniqKey="Christiansen C" first="Claus" last="Christiansen">Claus Christiansen</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Synarc, Centre for Clinical and Basic Research (CCBR)</s1><s2>Ballerup</s2><s3>DNK</s3><sZ>7 aut.</sZ></inist:fA14><country>Danemark</country></affiliation></author><author><name sortKey="Genant, Harry" sort="Genant, Harry" uniqKey="Genant H" first="Harry" last="Genant">Harry Genant</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Radiology, Medicine, Epidemiology and Orthopedic Surgery, University of California, San Francisco and Synarc</s1><s2>San Francisco, California</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Navarro, Federico" sort="Navarro, Federico" uniqKey="Navarro F" first="Federico" last="Navarro">Federico Navarro</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Rheumatology Department, Hospital Universitario Virgen Macarena</s1><s2>Sevilla</s2><s3>ESP</s3><sZ>9 aut.</sZ></inist:fA14><country>Espagne</country></affiliation></author><author><name sortKey="Nasonov, Evgeny" sort="Nasonov, Evgeny" uniqKey="Nasonov E" first="Evgeny" last="Nasonov">Evgeny Nasonov</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>State Institute of Rheumatology, Russian Academy of Medical Sciences</s1><s2>Moscow</s2><s3>RUS</s3><sZ>10 aut.</sZ></inist:fA14><country>Russie</country></affiliation></author><author><name sortKey="Sambrook, Philip N" sort="Sambrook, Philip N" uniqKey="Sambrook P" first="Philip N." last="Sambrook">Philip N. Sambrook</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Institute of Bone and Joint Research, Royal North Shore Hospital</s1><s2>St Leonards, NSW</s2><s3>AUS</s3><sZ>11 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Spector, Timothy D" sort="Spector, Timothy D" uniqKey="Spector T" first="Timothy D." last="Spector">Timothy D. Spector</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas' Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>12 aut.</sZ></inist:fA14><country>Royaume-Uni</country></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>MRC Lifecourse Epidemiology Unit, NIHR Musculoskeletal Biomedical Research Unit, University of Southampton, University of Oxford</s1><s2>Oxford</s2><s3>GBR</s3><sZ>13 aut.</sZ></inist:fA14><country>Royaume-Uni</country></affiliation></author></analytic><series><title level="j" type="main">Annals of the rheumatic diseases</title><title level="j" type="abbreviated">Ann. rheum. dis.</title><idno type="ISSN">0003-4967</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Annals of the rheumatic diseases</title><title level="j" type="abbreviated">Ann. rheum. dis.</title><idno type="ISSN">0003-4967</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Knee</term><term>Knee osteoarthritis</term><term>Osteoarthritis</term><term>Rheumatology</term><term>Strontium ranelate</term><term>Toxicity</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Gonarthrose</term><term>Ranélate de strontium</term><term>Toxicité</term><term>Traitement</term><term>Genou</term><term>Rhumatologie</term><term>Arthrose</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee Osteoarthrltis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p<sub>=</sub>0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p<sub>=</sub>0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p<sub>=</sub>0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0003-4967</s0></fA01><fA02 i1="01"><s0>ARDIAO</s0></fA02><fA03 i2="1"><s0>Ann. rheum. dis.</s0></fA03><fA05><s2>72</s2></fA05><fA06><s2>2</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial</s1></fA08><fA11 i1="01" i2="1"><s1>REGINSTER (Jean-Yves)</s1></fA11><fA11 i1="02" i2="1"><s1>BADURSKI (Janusz)</s1></fA11><fA11 i1="03" i2="1"><s1>BELLAMY (Nicholas)</s1></fA11><fA11 i1="04" i2="1"><s1>BENSEN (William)</s1></fA11><fA11 i1="05" i2="1"><s1>CHAPURLAT (Roland)</s1></fA11><fA11 i1="06" i2="1"><s1>CHEVALIER (Xavier)</s1></fA11><fA11 i1="07" i2="1"><s1>CHRISTIANSEN (Claus)</s1></fA11><fA11 i1="08" i2="1"><s1>GENANT (Harry)</s1></fA11><fA11 i1="09" i2="1"><s1>NAVARRO (Federico)</s1></fA11><fA11 i1="10" i2="1"><s1>NASONOV (Evgeny)</s1></fA11><fA11 i1="11" i2="1"><s1>SAMBROOK (Philip N.)</s1></fA11><fA11 i1="12" i2="1"><s1>SPECTOR (Timothy D.)</s1></fA11><fA11 i1="13" i2="1"><s1>COOPER (Cyrus)</s1></fA11><fA14 i1="01"><s1>Department of Public Health Epidemiology and Health Economics, University of Liege</s1><s2>Liege</s2><s3>BEL</s3><sZ>1 aut.</sZ></fA14><fA14 i1="02"><s1>Centre of Osteoporosis and Osteoarticular Diseases</s1><s2>Bialystok</s2><s3>POL</s3><sZ>2 aut.</sZ></fA14><fA14 i1="03"><s1>Centre of National Research on Disability (CONROD), University of Queensland, Herston</s1><s2>Queensland</s2><s3>AUS</s3><sZ>3 aut.</sZ></fA14><fA14 i1="04"><s1>DeGroot School of Medicine, McMaster University Hamilton</s1><s2>Hamilton, Ontario</s2><s3>CAN</s3><sZ>4 aut.</sZ></fA14><fA14 i1="05"><s1>INSERM UMR 1033, Service de Rhumatologie et Pathologie Osseuse, Hôpital Edouard Herriot, Universite de Lyon</s1><s2>Lyon</s2><s3>FRA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Service de Rhumatologie, Hôpital Henri Mondor</s1><s2>Créteil</s2><s3>FRA</s3><sZ>6 aut.</sZ></fA14><fA14 i1="07"><s1>Synarc, Centre for Clinical and Basic Research (CCBR)</s1><s2>Ballerup</s2><s3>DNK</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>Radiology, Medicine, Epidemiology and Orthopedic Surgery, University of California, San Francisco and Synarc</s1><s2>San Francisco, California</s2><s3>USA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="09"><s1>Rheumatology Department, Hospital Universitario Virgen Macarena</s1><s2>Sevilla</s2><s3>ESP</s3><sZ>9 aut.</sZ></fA14><fA14 i1="10"><s1>State Institute of Rheumatology, Russian Academy of Medical Sciences</s1><s2>Moscow</s2><s3>RUS</s3><sZ>10 aut.</sZ></fA14><fA14 i1="11"><s1>Institute of Bone and Joint Research, Royal North Shore Hospital</s1><s2>St Leonards, NSW</s2><s3>AUS</s3><sZ>11 aut.</sZ></fA14><fA14 i1="12"><s1>Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas' Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>12 aut.</sZ></fA14><fA14 i1="13"><s1>MRC Lifecourse Epidemiology Unit, NIHR Musculoskeletal Biomedical Research Unit, University of Southampton, University of Oxford</s1><s2>Oxford</s2><s3>GBR</s3><sZ>13 aut.</sZ></fA14><fA20><s1>179-186</s1></fA20><fA21><s1>2013</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>6381</s2><s5>354000506265310040</s5></fA43><fA44><s0>0000</s0><s1>© 2013 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>40 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>13-0074409</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Annals of the rheumatic diseases</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee Osteoarthrltis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5-5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: -0.23 (SD 0.56) mm; 2 g/day: -0.27 (SD 0.63) mm; placebo: -0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p<0.001 for 1 g/day and 0.10 (SE 0.04), 95% CI 0.02 to 0.19, p<sub>=</sub>0.018 for 2 g/day. Fewer radiological progressors were observed with strontium ranelate (p<0.001 and p<sub>=</sub>0.012 for 1 and 2 g/day). There were greater reductions in total WOMAC score (p=0.045), pain subscore (p=0.028), physical function subscore (p=0.099) and knee pain (p<sub>=</sub>0.065) with strontium ranelate 2 g/day. Strontium ranelate was well tolerated. Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.</s0></fC01><fC02 i1="01" i2="X"><s0>002B15E</s0></fC02><fC02 i1="02" i2="X"><s0>002B15I</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Gonarthrose</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Knee osteoarthritis</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Gonartrosi</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Ranélate de strontium</s0><s2>FR</s2><s5>04</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Strontium ranelate</s0><s2>FR</s2><s5>04</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Ranelat d'estronci</s0><s2>FR</s2><s5>04</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Toxicité</s0><s5>07</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Toxicity</s0><s5>07</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Toxicidad</s0><s5>07</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Traitement</s0><s5>08</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Treatment</s0><s5>08</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Tratamiento</s0><s5>08</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Genou</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Knee</s0><s5>09</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Rodilla</s0><s5>09</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Rhumatologie</s0><s5>13</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Rheumatology</s0><s5>13</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Reumatología</s0><s5>13</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Arthrose</s0><s5>30</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Osteoarthritis</s0><s5>30</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Artrosis</s0><s5>30</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Arthropathie</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Arthropathy</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Artropatía</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Pathologie du système ostéoarticulaire</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Diseases of the osteoarticular system</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Sistema osteoarticular patología</s0><s5>39</s5></fC07><fN21><s1>042</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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