Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients
Summary Objective Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Design Serum samples from patie...
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| Veröffentlicht in: | Osteoarthritis and cartilage 2017-06, Vol.25 (6), p.866-877 |
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| creator | Arends, R.H.G.P Karsdal, M.A Verburg, K.M West, C.R Bay-Jensen, A.C Keller, D.S |
| description | Summary Objective Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Design Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR ( n = 174) or matched patients who did not ( n = 321) were analyzed for bone, cartilage, soft tissue, and inflammation markers. Classification and Regression Tree (CART) analysis was used to identify biomarker phenotypes associated with TJR. Results At baseline, biomarker combinations for patients who did not use NSAIDs before starting tanezumab and used NSAIDs during tanezumab treatment |
| doi_str_mv | 10.1016/j.joca.2017.01.006 |
| format | Article |
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Design Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR ( n = 174) or matched patients who did not ( n = 321) were analyzed for bone, cartilage, soft tissue, and inflammation markers. Classification and Regression Tree (CART) analysis was used to identify biomarker phenotypes associated with TJR. Results At baseline, biomarker combinations for patients who did not use NSAIDs before starting tanezumab and used NSAIDs during tanezumab treatment <90 days (“nonNSAID”), identified 77% (95% confidence interval [CI]: 71–84%) of patients who experienced TJR and 77% (95% CI: 65–86%) who did not over a 6-month study period (on average). These biomarker combinations increased odds of identifying patients predicted to remain free of a TJR by 3.3-fold vs the baseline case–control dataset. In patients who used NSAIDs continuously (during screening and ≥90 days during tanezumab treatment), 64% (95% CI: 54–73%) who had TJR and 75% (95% CI: 68–83%) who did not were identified by biomarker combinations different from nonNSAID patients, with an increase in odds of identifying patients predicted to remain free of a TJR by two-fold vs the baseline case–control dataset. Conclusions Although validation on other cohorts is necessary, biomarkers may assist in identifying patients who will need TJR. The profiles suggest NSAID use increases importance of bone metabolism in TJR pathology.</description><identifier>ISSN: 1063-4584</identifier><identifier>EISSN: 1522-9653</identifier><identifier>DOI: 10.1016/j.joca.2017.01.006</identifier><identifier>PMID: 28115232</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analgesics - therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Antibodies, Monoclonal, Humanized - therapeutic use ; Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Biomarker ; Biomarkers - blood ; Bone Morphogenetic Proteins - blood ; Bone turnover ; C-Reactive Protein - metabolism ; Cartilage Oligomeric Matrix Protein - blood ; Collagen Type I - blood ; Collagen Type II - blood ; Collagen Type III - blood ; Connective tissue ; Disease Progression ; Female ; Genetic Markers ; Humans ; Intercellular Signaling Peptides and Proteins - blood ; Interleukin-6 - blood ; Logistic Models ; Male ; Matrix Metalloproteinase 9 - blood ; Middle Aged ; NSAID ; Osteoarthritis ; Osteoarthritis, Hip - blood ; Osteoarthritis, Hip - therapy ; Osteoarthritis, Knee - blood ; Osteoarthritis, Knee - therapy ; Osteocalcin - blood ; Peptide Fragments - blood ; Peptides - blood ; Procollagen - blood ; Prognosis ; Propensity Score ; Rheumatology ; Total joint replacement ; Vascular Endothelial Growth Factor A - blood</subject><ispartof>Osteoarthritis and cartilage, 2017-06, Vol.25 (6), p.866-877</ispartof><rights>Osteoarthritis Research Society International</rights><rights>2017 Osteoarthritis Research Society International</rights><rights>Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-65df3bbecfd4a20e44687ef56c3960f10de2e2cc8ecab9887fcbd409b28a51523</citedby><cites>FETCH-LOGICAL-c455t-65df3bbecfd4a20e44687ef56c3960f10de2e2cc8ecab9887fcbd409b28a51523</cites><orcidid>0000-0002-4764-5100</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.joca.2017.01.006$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28115232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arends, R.H.G.P</creatorcontrib><creatorcontrib>Karsdal, M.A</creatorcontrib><creatorcontrib>Verburg, K.M</creatorcontrib><creatorcontrib>West, C.R</creatorcontrib><creatorcontrib>Bay-Jensen, A.C</creatorcontrib><creatorcontrib>Keller, D.S</creatorcontrib><title>Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients</title><title>Osteoarthritis and cartilage</title><addtitle>Osteoarthritis Cartilage</addtitle><description>Summary Objective Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Design Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR ( n = 174) or matched patients who did not ( n = 321) were analyzed for bone, cartilage, soft tissue, and inflammation markers. Classification and Regression Tree (CART) analysis was used to identify biomarker phenotypes associated with TJR. Results At baseline, biomarker combinations for patients who did not use NSAIDs before starting tanezumab and used NSAIDs during tanezumab treatment <90 days (“nonNSAID”), identified 77% (95% confidence interval [CI]: 71–84%) of patients who experienced TJR and 77% (95% CI: 65–86%) who did not over a 6-month study period (on average). These biomarker combinations increased odds of identifying patients predicted to remain free of a TJR by 3.3-fold vs the baseline case–control dataset. In patients who used NSAIDs continuously (during screening and ≥90 days during tanezumab treatment), 64% (95% CI: 54–73%) who had TJR and 75% (95% CI: 68–83%) who did not were identified by biomarker combinations different from nonNSAID patients, with an increase in odds of identifying patients predicted to remain free of a TJR by two-fold vs the baseline case–control dataset. Conclusions Although validation on other cohorts is necessary, biomarkers may assist in identifying patients who will need TJR. The profiles suggest NSAID use increases importance of bone metabolism in TJR pathology.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analgesics - therapeutic use</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Arthroplasty, Replacement, Hip</subject><subject>Arthroplasty, Replacement, Knee</subject><subject>Biomarker</subject><subject>Biomarkers - blood</subject><subject>Bone Morphogenetic Proteins - blood</subject><subject>Bone turnover</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cartilage Oligomeric Matrix Protein - blood</subject><subject>Collagen Type I - blood</subject><subject>Collagen Type II - blood</subject><subject>Collagen Type III - blood</subject><subject>Connective tissue</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - blood</subject><subject>Interleukin-6 - blood</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>Middle Aged</subject><subject>NSAID</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis, Hip - blood</subject><subject>Osteoarthritis, Hip - therapy</subject><subject>Osteoarthritis, Knee - blood</subject><subject>Osteoarthritis, Knee - therapy</subject><subject>Osteocalcin - blood</subject><subject>Peptide Fragments - blood</subject><subject>Peptides - blood</subject><subject>Procollagen - blood</subject><subject>Prognosis</subject><subject>Propensity Score</subject><subject>Rheumatology</subject><subject>Total joint replacement</subject><subject>Vascular Endothelial Growth Factor A - blood</subject><issn>1063-4584</issn><issn>1522-9653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-P1SAUxYnROOPoF3BhWLppvUBL-xJjYib-mWQSF-qaUHpx6PSVJ5c3Zr69kDe6cOEKAuceOL_D2EsBrQCh3yztEp1tJYihBdEC6EfsXPRSNjvdq8dlD1o1XT92Z-wZ0QIASgh4ys7kKIpOyXNGVzNuOfjgbA5x49FzwhTX-KOcrHwKcW_TLSZ-SNGHFYlbouiCzTjzXyHf8BxzES4xbJknPKzW4b5Y8lDMKGO0Kd-kkAPxQ3mi3NBz9sTblfDFw3rBvn_88O3yc3P95dPV5fvrxnV9nxvdz15NEzo_d1YCdp0eB_S9dmqnwQuYUaJ0bkRnp904Dt5Ncwe7SY62r_Eu2OuTb_n7zyNSNvtADtfVbhiPZMSohYZxUFUqT1KXIlFCbw4plOT3RoCpsM1iKmxTYRsQpsAuQ68e_I_THue_I3_oFsHbkwBLyruAyZArBBzOIaHLZo7h__7v_hl3a9hqL7d4j7TEY9oKPyMMSQPma627ti0GVZvW6jcfx6jQ</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Arends, R.H.G.P</creator><creator>Karsdal, M.A</creator><creator>Verburg, K.M</creator><creator>West, C.R</creator><creator>Bay-Jensen, A.C</creator><creator>Keller, D.S</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4764-5100</orcidid></search><sort><creationdate>20170601</creationdate><title>Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients</title><author>Arends, R.H.G.P ; Karsdal, M.A ; Verburg, K.M ; West, C.R ; Bay-Jensen, A.C ; Keller, D.S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-65df3bbecfd4a20e44687ef56c3960f10de2e2cc8ecab9887fcbd409b28a51523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analgesics - therapeutic use</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Arthroplasty, Replacement, Hip</topic><topic>Arthroplasty, Replacement, Knee</topic><topic>Biomarker</topic><topic>Biomarkers - blood</topic><topic>Bone Morphogenetic Proteins - blood</topic><topic>Bone turnover</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cartilage Oligomeric Matrix Protein - blood</topic><topic>Collagen Type I - blood</topic><topic>Collagen Type II - blood</topic><topic>Collagen Type III - blood</topic><topic>Connective tissue</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - blood</topic><topic>Interleukin-6 - blood</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - blood</topic><topic>Middle Aged</topic><topic>NSAID</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis, Hip - blood</topic><topic>Osteoarthritis, Hip - therapy</topic><topic>Osteoarthritis, Knee - blood</topic><topic>Osteoarthritis, Knee - therapy</topic><topic>Osteocalcin - blood</topic><topic>Peptide Fragments - blood</topic><topic>Peptides - blood</topic><topic>Procollagen - blood</topic><topic>Prognosis</topic><topic>Propensity Score</topic><topic>Rheumatology</topic><topic>Total joint replacement</topic><topic>Vascular Endothelial Growth Factor A - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arends, R.H.G.P</creatorcontrib><creatorcontrib>Karsdal, M.A</creatorcontrib><creatorcontrib>Verburg, K.M</creatorcontrib><creatorcontrib>West, C.R</creatorcontrib><creatorcontrib>Bay-Jensen, A.C</creatorcontrib><creatorcontrib>Keller, D.S</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Osteoarthritis and cartilage</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arends, R.H.G.P</au><au>Karsdal, M.A</au><au>Verburg, K.M</au><au>West, C.R</au><au>Bay-Jensen, A.C</au><au>Keller, D.S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients</atitle><jtitle>Osteoarthritis and cartilage</jtitle><addtitle>Osteoarthritis Cartilage</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>25</volume><issue>6</issue><spage>866</spage><epage>877</epage><pages>866-877</pages><issn>1063-4584</issn><eissn>1522-9653</eissn><abstract>Summary Objective Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Design Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR ( n = 174) or matched patients who did not ( n = 321) were analyzed for bone, cartilage, soft tissue, and inflammation markers. Classification and Regression Tree (CART) analysis was used to identify biomarker phenotypes associated with TJR. Results At baseline, biomarker combinations for patients who did not use NSAIDs before starting tanezumab and used NSAIDs during tanezumab treatment <90 days (“nonNSAID”), identified 77% (95% confidence interval [CI]: 71–84%) of patients who experienced TJR and 77% (95% CI: 65–86%) who did not over a 6-month study period (on average). These biomarker combinations increased odds of identifying patients predicted to remain free of a TJR by 3.3-fold vs the baseline case–control dataset. In patients who used NSAIDs continuously (during screening and ≥90 days during tanezumab treatment), 64% (95% CI: 54–73%) who had TJR and 75% (95% CI: 68–83%) who did not were identified by biomarker combinations different from nonNSAID patients, with an increase in odds of identifying patients predicted to remain free of a TJR by two-fold vs the baseline case–control dataset. Conclusions Although validation on other cohorts is necessary, biomarkers may assist in identifying patients who will need TJR. The profiles suggest NSAID use increases importance of bone metabolism in TJR pathology.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28115232</pmid><doi>10.1016/j.joca.2017.01.006</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4764-5100</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Analgesics - therapeutic use Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Antibodies, Monoclonal, Humanized - therapeutic use Arthroplasty, Replacement, Hip Arthroplasty, Replacement, Knee Biomarker Biomarkers - blood Bone Morphogenetic Proteins - blood Bone turnover C-Reactive Protein - metabolism Cartilage Oligomeric Matrix Protein - blood Collagen Type I - blood Collagen Type II - blood Collagen Type III - blood Connective tissue Disease Progression Female Genetic Markers Humans Intercellular Signaling Peptides and Proteins - blood Interleukin-6 - blood Logistic Models Male Matrix Metalloproteinase 9 - blood Middle Aged NSAID Osteoarthritis Osteoarthritis, Hip - blood Osteoarthritis, Hip - therapy Osteoarthritis, Knee - blood Osteoarthritis, Knee - therapy Osteocalcin - blood Peptide Fragments - blood Peptides - blood Procollagen - blood Prognosis Propensity Score Rheumatology Total joint replacement Vascular Endothelial Growth Factor A - blood |
| title | Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients |
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