ABSTRACT
I. Introduction ............................................................................. 60
II. Treatment Protocols ................................................................. 60
III. Effects of PTH on Cancellous Bone in OVX Rats ................... 61
IV. Effects of PTH on Cortical Bone in OVX Rats ........................ 69
V. Effects of PTH on Bone Strength in OVX Rats ....................... 71
VI. Concurrent Treatment of OVX Rats with PTH and Antiresorptive Agents ............................................................. 72
VII. Maintenance of Bone After Withdrawal of PTH Treatment ......................................................................... 73
VIII. Potential Mediators of the Skeletal Effects of PTH Treatment in OVX Rats ............................................................ 74
IX. Side Effects of PTH Treatment ................................................ 74
X. Summary and Conclusions...................................................... 75
References ........................................................................................... 77
PTH has traditionally been considered a bone catabolic hormone due to its well-known role in calcium homeostasis of increasing serum calcium through a stimulatory effect on bone resorption.1 PTH was also hypothesized to be involved in the pathogenesis of postmenopausal osteoporosis in that the skeleton was thought to be more sensitive to the catabolic actions of PTH in the estrogen-deplete state.2,3 In view of these concepts, it is somewhat surprising that PTH is currently being investigated as a therapy for postmenopausal osteoporosis. However, in contrast to its more widely known bone catabolic effects, PTH has also been reported to have anabolic effects on the skeleton. The first such report was published in 1932 by Selye.4 His initial findings in intact rats have since been confirmed by many investigators who detected substantial increases in bone mass in rats treated intermittently with PTH.5-12 Since agents with an anabolic effect on bone are rare, it is important to evaluate the therapeutic potential of PTH for osteoporosis. As an essential step in this process, the skeletal effects of PTH should be thoroughly characterized in the ovariectomized (OVX) rat, a widely used animal model for postmenopausal bone loss.13,14 The results of these studies are summarized below.
