Atsushi Watanabe,
Shigeki Yoneyama,
Mikio Nakajima,
Norihiro Sato,
Ryoko Takao-Kawabata, Yukihiro Isogai,
Aki Sakurai-Tanikawa,
Kazuhiro Higuchi,
Akihito Shimoi,
Hideyuki Yamatoya,
Kenji Yoshida,
Terutomo Kohira
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ABSTRACT: 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.
The Journal of Toxicological Sciences 01/2012; 37(3):617-29. · 1.52 Impact Factor
