Teriparatide and bisphosphonates are osteoporosis medications that increase bone 
mineral density (BMD) and prevent fracture, but each has a different mechanism 
of action. Teriparatide promotes bone formation, while bisphosphonates suppress 
bone resorption. In the clinical setting, however, drug selection is not always 
tailored to the particular clinical condition of the patient or mechanism of 
action of the drug. We compared the effects of teriparatide and the 
bisphosphonate risedronate on bone metabolism using two ovariectomized rat 
models to elucidate the optimal use of these two drugs in the clinical setting. 
We first performed dose-finding experiments to determine the equivalent 
effective doses of each drug (5.6 and 3.0 µg/kg for teriparatide and 
risedronate, respectively). We then compared the effects of these doses on bone 
metabolism after subcutaneous administration three times weekly for 4 months 
starting either the day after ovariectomy (preventive study) or 12 months after 
ovariectomy (therapeutic study). The increase in proximal tibial BMD under the 
physical conditions that increased bone turnover at 1 to 2 months after 
ovariectomy was greater in the risedronate group than in the teriparatide group. 
In contrast, the increases in lumbar vertebral BMD and bone strength under the 
physical conditions that significantly decreased BMD and bone strength at 
12 months after ovariectomy were greater in the teriparatide group than in the 
risedronate group. The present study provides important information on the 
selection of antiosteoporotic drugs, including teriparatide and risedronate, in 
treatment protocols tailored to the clinical conditions of patients and drug 
mechanisms.