Effect of parathyroid hormone (hPTH[1-84]) treatment on bone mass and strength in ovariectomized rats

Skeletal fragility in osteoporotic patients is a prominent underlying cause of low-trauma fractures of most bone sites in humans. Clinical research is now focused on developing treatment strategies, including anabolic agents such as parathyroid hormone (PTH), to recover osteoporosis related bone los s. Female Sprague-Dawley rats (4.5 mos old) were allowed to become osteopen ic for 10 wk postovariectomy. Eight rats were killed at the time of ovariec tomy (-10 wk) as a baseline control; sham and ovariectomized (OVX) groups w ere killed at wk 0. Eight rats per group (sham, OVX + vehicle, OVX + hPTH [ 5 d/wk], and OVX + hPTH [3 d/wk]) were killed after 4, 8, 14, and 20 wk of treatment with 50 mug/kg of human parathyroid hormone (hPTH[1-84]). Bone mi neral content and density were measured only in the vertebral body. Bone st rength was evaluated in the vertebral body, femoral diaphysis, femoral neck , and distal femur. Significant, lasting osteopenia developed in the verteb ral body of OVX rats by 10 wk postovariectomy. Bone mineral density of the vertebral body partially recovered by 8 wk and fully recovered to that seen in sham animals only by 20 wk posttreatment with either a 5 or 3 d/wk dosi ng schedule of PTH[1-84]. Therefore, hPTH[1-84] (50 mug/kg) given either 3 or 5 d/wk fully restores vertebral and femoral bone strength in osteopenic OVX rats.