In rats,
teriparatide [rhPTH(1-34)] causes marked increases in bone mass and
osteosarcoma. In primates,
teriparatide causes lesser increases in bone mass, and
osteosarcomas have not been reported. Previous studies in primates were not designed to detect bone
tumors and did not include a prolonged post-treatment observation period to determine whether
tumors would arise after
cessation of treatment. Ovariectomized (OVX), skeletally mature, cynomolgus monkeys (
n = 30 per group) were given
teriparatide for 18 mo at either 0 or 5 microg/kg/d subcutaneously. After 18 mo of treatment, subgroups of six monkeys from both groups were killed and evaluated, whereas all remaining monkeys entered a 3-yr observation period in which they did not receive
teriparatide. Surveillance for bone
tumors was accomplished with plain film radiographs, visual examination of the skeleton at necropsy, and histologic evaluation of multiple skeletal sites. Quantitative assessments of bone mass, architecture, and strength were also performed. After the 18-mo treatment period, vertebral BMD, BMC, and strength (ultimate load) were increased by 29%, 36%, and 52%, respectively, compared with OVX controls. Proximal femur BMD, BMC, and strength were also increased by 15%, 28% and 33%, respectively. After 3 yr without treatment, no differences in bone mass or strength at the vertebra were observed relative to OVX controls; however, the femoral neck showed significant persistence in stiffness (20%), BMC (14%), and trabecular BV/TV (53%), indicating a retention of
teriparatide efficacy at the hip. Radiographs and histology did not identify any bone proliferative lesions or microscopic lesions of
osteosarcoma at the end of the treatment or observation period. These data indicate that
teriparatide did not induce bone proliferative lesions over a 4.5-yr interval of observation, including 18 mo of treatment and 3 yr of follow-up observation. Bone analyses confirmed that
teriparatide caused increases in bone mass and strength, consistent with previous studies. During the withdrawal phase, beneficial effects of
teriparatide treatment on the vertebra were lost; however, some of the beneficial effects on the proximal femur persisted for 3 yr after
cessation of treatment. Although the lack of bone
tumors in this study provides some additional reassurance regarding the safety of
teriparatide for the primate skeleton, the small group size and other limitations of this, or any other animal study, limit the ability to draw definitive conclusions regarding the risk of bone
tumor developments in patients.