Bone Neoplasms in F344 Rats Given Teriparatide [rhPTH(1-34)] Are Dependent on Duration of Treatment and Dose

John L. Vahle, Gerald G. Long, George Sandusky, Michael Westmore, Yanfei Linda ma, Masahiko Sato

Research output: Contribution to journalArticle

226 Scopus citations

Abstract

A long-term study was conducted in female F344 rats to determine the relative importance of dose, treatment duration, and age at initiation of treatment on the incidence of teriparatide [rhPTH[1-34)]-induced bone proliferative lesions. Treatment groups consisted of different combinations of dose (0, 5, or 30 μg/kg/d), treatment duration (6, 20, or 24 months) and age at initiation of treatment (2 or 6 months of age). The primary endpoints were the incidence of bone neoplasms and effects on bone mass and structure as evaluated by quantitative computed tomography and histomorphometery. Significant increases in the incidence of bone tumors (osteoma, osteoblastoma, and osteosarcoma) occurred in rats treated with 30 μg/kg for 20 or 24 months. No neoplasms were found when the 5 μg/kg treatment was initiated at 6 months of age and continued for either 6 or 20 months (up to 70% of life span). This treatment regimen defined a “no-effect” dose for neoplasm formation that nevertheless resulted in substantial increases in bone mass. These results demonstrate that treatment duration and administered dose are the most important factors in the teriparatide-induced bone tumors in rats.

Original languageEnglish (US)
Pages (from-to)426-438
Number of pages13
JournalToxicologic Pathology
Volume32
Issue number4
DOIs
StatePublished - Jun 2004

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Keywords

  • PTH
  • bone
  • neoplasms
  • osteoporosis treatment
  • osteosarcoma
  • rat
  • teriparatide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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