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The effects of such agents on osseointegration is less well understood. The purpose of the current study was to investigate whether osteoprotegerin (OPG), an osteoclast inhibitor, enhances the known anabolic effects of mechanical loading (VEH) and intermittent PTH (iPTH) using a well\u2010established rabbit model of osseointegration. In the first set of experiments, OPG was administered either alone or combined with iPTH to study its effects on measured bone mass. The second set of experiments was conducted using a higher dosage of OPG (10\u2009mg\/kg) to explore its early impact at the cellular and molecular levels. All subjects had mechanical load applied to the implant on one extremity, and no load applied on the contralateral side. In the first set of experiments, OPG alone decreased peri\u2010implant bone mass compared to the mechanical loading group, whereas OPG\u2009+\u2009iPTH increased peri\u2010implant bone mass compared to the OPG group. In the second set of experiments, high\u2010dose OPG significantly decreased osteoclast number (\u221274.3%) at 1\u2009week. However, this effect was not sustained as osteoclast number returned to baseline by 2\u2009weeks. These results suggest that systemic administration of OPG does not enhance osseointegration, but rather has a detrimental effect.<\/jats:p>","DOI":"10.1002\/jor.24884","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T19:28:19Z","timestamp":1602617299000},"page":"1611-1621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic osteoprotegerin does not improve peri\u2010implant bone volume or osseointegration in rabbits"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7225-9084","authenticated-orcid":false,"given":"Joseph H.","family":"Choi","sequence":"first","affiliation":[{"name":"Hospital for Special Surgery  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5668-075X","authenticated-orcid":false,"given":"Zhiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery  New York New York USA"},{"name":"Orthopaedic Department, Beijing Chaoyang Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick P.","family":"Ross","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein C. 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