Osteosarcoma in Sprague-Dawley rats after long-term treatment with teriparatide (human parathyroid hormone (1-34)).
Teriparatide, a therapeutic agent for osteoporosis, has been reported to increase the incidences of bone neoplasms such as osteosarcoma when administered subcutaneously to Fischer 344 (F344) rats for a long term, but its non-carcinogenic dose level following 2-year daily administration has not been established. Here we report detailed studies on the carcinogenicity of teriparatide following long-term administration. When teriparatide was administered subcutaneously to male and female Sprague-Dawley (SD) rats daily for 2 years, the incidence of osteosarcoma was increased at 13.6 µg/kg/day. The non-carcinogenic dose level was 4.5 µg/kg/day for both males and females. The development of osteosarcoma in SD rats depends on the dose level of, and treatment duration with, teriparatide. Responses of the bones to teriparatide were similar between F344 and SD rats in many aspects. These results suggested that the carcinogenic potential of teriparatide in SD rats is essentially the same as in F344 rats.
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan. watanabe.ab@om.asahi-kasei.com.jp
Atsushi
A
Watanabe
Shigeki
S
Yoneyama
Mikio
M
Nakajima
Norihiro
N
Sato
Ryoko
R
Takao-Kawabata
Yukihiro
Y
Isogai
Aki
A
Sakurai-Tanikawa
Kazuhiro
K
Higuchi
Akihito
A
Shimoi
Hideyuki
H
Yamatoya
Kenji
K
Yoshida
Terutomo
T
Kohira
D000818:Animals; D001859:Bone Neoplasms / Q000139:chemically induced / Q000473:pathology*; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D012516:Osteosarcoma / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors
D002273:Carcinogens; D019379:Teriparatide