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As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH(1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75- \u03bcg\/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.<\/jats:p>","DOI":"10.1080\/01926230252929882","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:35:35Z","timestamp":1027686935000},"page":"312-321","source":"Crossref","is-referenced-by-count":590,"title":["Skeletal Changes in Rats Given Daily Subcutaneous Injections of Recombinant Human Parathyroid Hormone (1-34) for 2 Years and Relevance to Human Safety"],"prefix":"10.1177","volume":"30","author":[{"given":"John L.","family":"Vahle","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald G.","family":"Long","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie K.","family":"Young","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Francis","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery A.","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Westmore","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei Linda","family":"Ma","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Greenfield, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Nold","sequence":"additional","affiliation":[{"name":"Pathology Associates \u2014A Charles River Company, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2002,4,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(97)00121-X"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(94)00036-Y"},{"key":"atypb3","unstructured":"Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, Mackenzie WF (eds). 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