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

208 Citations (Scopus)

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 - Jul 2004
Externally publishedYes

Fingerprint

Teriparatide
Bone Neoplasms
Inbred F344 Rats
Rats
Bone
Bone and Bones
Incidence
Osteoblastoma
Tumors
Neoplasms
Osteosarcoma
Tomography

Keywords

  • Bone
  • Neoplasms
  • Osteoporosis treatment
  • Osteosarcoma
  • PTH
  • Rat
  • Teriparatide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. / Vahle, John L.; Long, Gerald G.; Sandusky, George; Westmore, Michael; Ma, Yanfei Linda; Sato, Masahiko.

In: Toxicologic Pathology, Vol. 32, No. 4, 07.2004, p. 426-438.

Research output: Contribution to journalArticle

Vahle, John L. ; Long, Gerald G. ; Sandusky, George ; Westmore, Michael ; Ma, Yanfei Linda ; Sato, Masahiko. / Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. In: Toxicologic Pathology. 2004 ; Vol. 32, No. 4. pp. 426-438.
@article{907ae78b33bc40288d9c730ba7aa65ce,
title = "Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose",
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.",
keywords = "Bone, Neoplasms, Osteoporosis treatment, Osteosarcoma, PTH, Rat, Teriparatide",
author = "Vahle, {John L.} and Long, {Gerald G.} and George Sandusky and Michael Westmore and Ma, {Yanfei Linda} and Masahiko Sato",
year = "2004",
month = "7",
doi = "10.1080/01926230490462138",
language = "English (US)",
volume = "32",
pages = "426--438",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications Inc.",
number = "4",

}

TY - JOUR

T1 - Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose

AU - Vahle, John L.

AU - Long, Gerald G.

AU - Sandusky, George

AU - Westmore, Michael

AU - Ma, Yanfei Linda

AU - Sato, Masahiko

PY - 2004/7

Y1 - 2004/7

N2 - 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.

AB - 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.

KW - Bone

KW - Neoplasms

KW - Osteoporosis treatment

KW - Osteosarcoma

KW - PTH

KW - Rat

KW - Teriparatide

UR - http://www.scopus.com/inward/record.url?scp=3242887547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242887547&partnerID=8YFLogxK

U2 - 10.1080/01926230490462138

DO - 10.1080/01926230490462138

M3 - Article

VL - 32

SP - 426

EP - 438

JO - Toxicologic Pathology

JF - Toxicologic Pathology

SN - 0192-6233

IS - 4

ER -