Anabolic agents and osteoporosis: quo vadis?

There are preclinical studies and limited clinical experiences with bone and muscle anabolic agents (e.g., parathyroid hormone (PTH), sodium fluoride (NaF), prostaglandins (PGs), growth hormones (GH), etc.) that show they have significant advantages over antiremodeling agents in patients with established osteoporosis. The strength of anabolic therapy is as follows: it rapidly reverses bone loss in laboratory animal models and humans, the quality of bone with some agents is believed to be normal, an increase in bone strength in animal models, and a reduction of spinal fracture rate with PTH. The weaknesses of this therapy are high cost, poor understanding of mechanism of action, parenteral mode of administration, rapid bone loss following termination of treatment, abnormal quality of bone, lack of tissue specificity, and undesirable side effects. Both animal and clinical studies have shown one can preserve the bone gain following termination of treatment with antiremodeling agents or exercise based on the lose, restore and maintain (LRM) concept. However, the more important efficacy issues which need to be addressed are tissue specificity and reduction of undesirable side effects. This report will address these issues with the suggestions that the potentiation of the mechanical loading osteogenic response by anabolic agents can overcome the disadvantages which accompany the use of anabolic agents. In addition, the possible role of nitric oxide (NO), an agent required for mechanical loading-induced bone formation, will be discussed.