This study elucidates the effect of PTH, estrogen, and the bisphosphonate Risedronate (NE-58095) on femoral neck bone strength in ovariectomized (OVX) rats aged 90 days at the beginning of the investigation. Furthermore, the effects of these monotherapies were compared with those of concurrent treatment with PTH plus estrogen or PTH plus bisphosphonate. Four weeks after surgery the rats were randomized into a sham-operated vehicle-treated group, an OVX vehicle-treated group, and the various treatment groups and followed for 5 and 15 weeks. The proximal one-third of the left femur was then subjected to geometrical measurements and biomechanical testing. Neither ovariectomy nor the different treatment regimens influenced femoral neck geometry. OVX rats exhibited a decrease in femoral neck bone strength compared with control rats. This was most evident after 5 weeks. Treatment of OVX rats with Risedronate or estrogen alone tended to increase bone strength to control level, though these findings were nonsignificant. In contrast, treatment with PTH showed a highly significant increase in femoral neck biomechanical competence. Concurrent treatment with PTH plus estrogen or PTH plus Risedronate also significantly increased the femoral neck bone strength, but neither showed any advantage over treatment with PTH alone. It is concluded that treatment with PTH increases the strength of the femoral neck in estrogen-depleted rats in a highly significant manner, and that this effect is much more pronounced than the effect of the two antiresorptive agents estrogen or Risedronate. Thus, these findings provide further support for the anabolic effect of PTH and add weight to the argument for the promising potential of PTH in the treatment of postmenopausal osteoporosis.