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An experimental model was used in which osteolytic tumors are known to stimulate osteoclastogenesis and grow in femora of osteoclast\u2010deficient mice (<jats:italic>op<\/jats:italic>\/<jats:italic>op<\/jats:italic>). Osteoprotegerin treatment decreased the number of osteoclasts by 90% (p &lt; 0.0007) at sites of tumor in a dose\u2010dependent manner and decreased bone tumor area by greater than 90% (p &lt; 0.003). The mechanisms through which osteoprotegerin decreased osteoclast formation in tumor\u2010bearing animals included (a) an osteoprotegerin\u2010mediated, systemic reduction in the number of splenic and bone marrow\u2010residing osteoclast precursor cells. (b) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K and receptor activator of NFkB mRNA expression, and (c) a decrease in osteoprotegerin ligand mRNA at sites of tumor. These findings suggest that osteoprotegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precursors and reduces production of osteoprotegerin ligand at sites of osteolytic tumor.<\/jats:p>","DOI":"10.1002\/jor.1100180617","type":"journal-article","created":{"date-parts":[[2005,2,24]],"date-time":"2005-02-24T14:48:01Z","timestamp":1109256481000},"page":"967-976","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Osteoprotegerin inhibits tumor\u2010induced osteoclastogenesis and bone tumor growth in osteopetrotic mice"],"prefix":"10.1002","volume":"18","author":[{"given":"Denis R.","family":"Clohisy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret 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