The anabolic effects of parathyroid hormone therapy.

PTH represents an important new advance in the therapy of osteoporosis. As an anabolic agent, its potential might be substantially greater than that of antiresorptive agents. Clear evidence in human trials now documents the ability of PTH to stimulate cancellous bone formation and to reduce fractures. Because antiresorptive agents and PTH work by distinct mechanisms of action, it is possible that the combination of these agents could be significantly more potent than either agent alone. There are other unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. In addition, more large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. More information is also required to determine the possible need for antiresorptive therapy after PTH. Protocols to consider PTH as an intermittent recycling therapy would be of interest. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al [78] have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Ultimately, when the anabolic and catabolic mechanisms of PTH can be clearly distinguished, both mechanistically and in molecular terms, it may be possible to develop PTH analogs that are more purely anabolic.