{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:00:55Z","timestamp":1785366055051,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2002,7,11]],"date-time":"2002-07-11T00:00:00Z","timestamp":1026345600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the effect of different dosages and treatment schedules of osteoprotegerin (OPG) on joint preservation in an experimental model of adjuvant\u2010induced arthritis (AIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Lewis rats with AIA (6\u20138 per group) were treated with a subcutaneous bolus of recombinant human OPG according to one of the following schedules: daily OPG (an efficacious regimen) starting at disease onset (days 9\u201315), early intervention (days 9\u201311), delayed intervention (days 13\u201315), and extended therapy (days 9\u201322). Inflammation (hind paw swelling) was quantified throughout the clinical course; osteoporosis (bone mineral density [BMD], by quantitative dual x\u2010ray absorptiometry) and morphologic appraisals of inflammation, bone damage, intralesional osteoclasts (by semiquantitative histopathologic scoring), and integrity of the articular cartilage matrix (by retention of toluidine blue stain) were determined in histology sections of arthritic hind paws.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OPG provided dose\u2010 and schedule\u2010dependent preservation of BMD and periarticular bone while essentially eliminating intralesional osteoclasts. Dosages \u22652.5 mg\/kg\/day preserved or enhanced BMD and prevented essentially all erosions. A dosage of 4 mg\/kg\/day protected joint integrity to a comparable degree when given for 7 (days 9\u201315) or 14 (days 9\u201322) consecutive days. At this dosage, early intervention (days 9\u201311) was twice as effective as delayed intervention (days 13\u201315) at preventing joint dissolution. Erosions and osteoclast scores were greatly decreased for 26 days (measured from the first treatment) after 7 or 14 daily doses of OPG (4 mg\/kg\/day). OPG treatment also prevented loss of cartilage matrix proteoglycans, an indirect consequence of protecting the subchondral bone. No OPG dosage or regimen alleviated weight loss, inflammation, or periosteal osteophyte production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data indicate that OPG preserves articular bone and (indirectly) articular cartilage in arthritic joints in a dose\u2010 and schedule\u2010dependent manner, halts bone erosion when given at any point during the course of arthritis, produces sustained antierosive activity after a short course, and is most effective when initiated early in the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10369","type":"journal-article","created":{"date-parts":[[2002,9,11]],"date-time":"2002-09-11T02:05:28Z","timestamp":1031709928000},"page":"1926-1936","source":"Crossref","is-referenced-by-count":63,"title":["Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis"],"prefix":"10.1002","volume":"46","author":[{"given":"Giuseppe","family":"Campagnuolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Bolon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Feige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,7,11]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar134"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/40.6.623"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.1.2"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.3.527"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3540"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.20.3.0367"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1260"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/16852"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1566"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/46303"},{"issue":"9","key":"e_1_2_6_15_2","first-page":"S267","article-title":"Fc\u2010osteoprotegerin fusion protein (Fc\u2010OPG) reduces osteoclast numbers and prevents bone destruction in rats with collagen\u2010induced arthritis","volume":"44","author":"Romas E","year":"2001","journal-title":"Arthritis Rheum"},{"key":"e_1_2_6_16_2","first-page":"4432","article-title":"Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis","volume":"61","author":"Morony S","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0245"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.2.348"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270902"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280105"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7404"},{"key":"e_1_2_6_22_2","first-page":"264","article-title":"Abnormal bone remodelling in inflammatory arthritis","volume":"41","author":"Bogoch ER","year":"1998","journal-title":"Can J Surg"},{"key":"e_1_2_6_23_2","first-page":"943","article-title":"Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis","volume":"152","author":"Gravallese EM","year":"1998","journal-title":"Am J Pathol"},{"key":"e_1_2_6_24_2","first-page":"751","article-title":"Induction of abundant osteoclast\u2010like multinucleated giant cells in adjuvant arthritic rats with accompanying disordered high bone turnover","volume":"13","author":"Kuratani T","year":"1998","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_25_2","first-page":"1154","article-title":"Osteoclast\u2010like cells in murine collagen induced arthritis","volume":"25","author":"Suzuki Y","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.47.211"},{"issue":"9","key":"e_1_2_6_27_2","first-page":"S233","article-title":"IL\u20101ra and PEG sTNF\u2010RI reduce osteoclast numbers in rats with adjuvant arthritis","volume":"43","author":"Bolon B","year":"2000","journal-title":"Arthritis Rheum"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200004)43:4<821::AID-ANR12>3.0.CO;2-T"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.6.715"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2523::AID-ANR20>3.0.CO;2-Z"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200002)43:2<259::AID-ANR4>3.0.CO;2-W"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00210-0"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007740070018"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900473"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.55.11.816"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH672>3.0.CO;2-W"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00306-9"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.3.5837"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9294"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64556-7"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000629"},{"key":"e_1_2_6_42_2","first-page":"599","article-title":"Preferred sites and measurements for rapid osteoclast quantification in rat adjuvant arthritis","volume":"38","author":"Bolon B","year":"2001","journal-title":"Vet Pathol"},{"key":"e_1_2_6_43_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/ard.60.90003.iii81","article-title":"Osteoprotegerin","volume":"60","author":"Feige U","year":"2001","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.3.495"},{"key":"e_1_2_6_45_2","first-page":"1690","article-title":"Osteoclastogenesis in iliac bone marrow of patients with rheumatoid arthritis","volume":"24","author":"Toritsuka Y","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00832003"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2"},{"issue":"9","key":"e_1_2_6_48_2","first-page":"S241","article-title":"Comparison of etanercept vs. methotrexate in early rheumatoid arthritis using gadolinium\u2010enhanced magnetic resonance imaging","volume":"42","author":"Peterfy C","year":"1999","journal-title":"Arthritis Rheum"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/31.10.653"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010153200"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1623"},{"key":"e_1_2_6_52_2","first-page":"677","article-title":"Osteoclasts in normal and adjuvant arthritis bone tissues express the mRNA for both type I and II interleukin\u20101 receptors","volume":"75","author":"Xu LX","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.2.275"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008198200"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)61511-5"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.10369","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.10369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T23:23:42Z","timestamp":1733786622000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.10369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,7]]},"references-count":54,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2002,7]]}},"alternative-id":["10.1002\/art.10369"],"URL":"https:\/\/doi.org\/10.1002\/art.10369","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,7]]}}}