Prolonged treatment with human parathyroid hormone (hPTH) in rats results in 
development of bone tumors, though this finding has not been supported by 
clinical experience. The PTH type 1 receptor agonist abaloparatide, selected for 
its bone anabolic activity, is under clinical development to treat 
postmenopausal women with osteoporosis. To determine the carcinogenic potential 
of abaloparatide, Fischer (F344) rats were administered SC daily abaloparatide 
at doses of 0, 10, 25, and 50 μg/kg or 30 μg/kg hPTH(1-34) as a positive control 
for up to 2 years. Robust increases in bone density were achieved at all 
abaloparatide doses and with hPTH(1-34). Comprehensive histopathological 
analysis reflected a comparable continuum of proliferative changes in bone, 
mostly osteosarcoma, in both abaloparatide and hPTH(1-34) treated rats. 
Comparing the effects of abaloparatide and hPTH(1-34) at the 25 and 30 μg/kg 
respective doses, representing similar exposure multiples to the human 
therapeutic doses, revealed similar osteosarcoma-associated mortality, tumor 
incidence, age at first occurrence, and metastatic potential. There were no 
increases in the incidence of non-bone tumors with abaloparatide compared to 
vehicle. Thus, near life-long treatment with abaloparatide in rats resulted in 
dose and time dependent formation of osteosarcomas, with a comparable response 
to hPTH(1-34) at similar exposure.