{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:03:24Z","timestamp":1790870604698,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,4,10]],"date-time":"2008-04-10T00:00:00Z","timestamp":1207785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aseptic loosening of total joint replacements is caused by wear debris\u2010induced osteoclastic bone resorption, for which bisphosphonates (BPs) and RANK antagonists have been developed. Although BPs are effective in preventing metabolic bone loss, they are less effective for inflammatory bone loss. Because this difference has been attributed to the antiapoptotic inflammatory signals that protect osteoclasts from BP\u2010induced apoptosis, but not RANK antagonists, we tested the hypothesis that osteoprotegerin (OPG) is more effective in preventing wear debris\u2010induced osteolysis than zoledronic acid (ZA) or alendronate (Aln) in the murine calvaria model using in vivo micro\u2010CT and traditional histology. Although micro\u2010CT proved to be incompatible with titanium (Ti) particles, we were able to demonstrate a 3.2\u2010fold increase in osteolytic volume over 10 days induced by polyethylene (PE) particles versus sham controls (0.49\u2009\u00b1\u20090.23mm\n                    <jats:sup>3<\/jats:sup>\n                    versus 0.15\u2009\u00b1\u20090.067mm\n                    <jats:sup>3<\/jats:sup>\n                    ;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Although OPG and high\u2010dose ZA completely inhibited this PE\u2010induced osteolysis (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), pharmacological doses of ZA and Aln were less effective but still reached statistical significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Traditional histomorphometry of the sagital suture area of calvaria from both Ti and PE\u2010treated mice confirmed the remarkable suppression of resorption by OPG (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) versus the lack of effect by physiological BPs. The differences in drug effects on osteolysis were largely explained by the significant difference in osteoclast numbers observed between OPG versus BPs in both Ti\u2010 and PE\u2010treated calvaria; and linear regression analyses that demonstrated a highly significant correlation between osteolysis volume and sagittal suture area versus osteoclast numbers (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). \u00a9 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1340\u20131346, 2008\n                  <\/jats:p>","DOI":"10.1002\/jor.20620","type":"journal-article","created":{"date-parts":[[2008,4,10]],"date-time":"2008-04-10T19:46:33Z","timestamp":1207856793000},"page":"1340-1346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Differential effects of biologic versus bisphosphonate inhibition of wear debris\u2010induced osteolysis assessed by longitudinal micro\u2010CT"],"prefix":"10.1002","volume":"26","author":[{"given":"Ryosuke","family":"Tsutsumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Hock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Dustin","family":"Bechtold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"Proulx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan V.","family":"Bukata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"A. 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