Bisphosphonates in osteoporosis: an introduction.

Abstract

The bisphosphonates are compounds characterized by a P-C-P bond. By substitution of the hydrogens on the carbon atom it is possible to synthesize a variety of bisphosphonates each with its own distinct physicochemical, pharmacological, and toxicological characteristics. The bisphosphonates investigated for use in bone disease have, in general the following properties: they bind strongly onto bone mineral, inhibit calcium phosphate crystal formation and dissolution, inhibit normal and ectopic mineralization (probably through a physicochemical inhibition of crystal growth), and inhibit bone resorption. The last effect is cell-mediated, the exact mechanism being unknown, and is exquisitely dependent upon bisphosphonates used. Various bisphosphonates have been investigated extensively in animals for a possible use in osteoporosis. They were found not only to increase the balance of calcium in normal rats but also to prevent various types of experimental osteoporosis, such as occurs after immobilization, ovariectomy, or administration of corticosteroids. the toxicity of these compounds is relatively low, probably because they are cleared rapidly from the plasma to be deposited preferentially in the bone, where they remain over a long time. In man, bisphosphonates are used successfully in diseases with increased bone turnover, such as Paget's disease and tumoral bone disease. Recently, a few have been investigated in osteoporosis. They were shown not only to inhibit bone loss but also to increase bone mass. The effect on the rate of fractures is not yet proven, but the first results look promising. Many issues as yet unsolved, will be essential for the choice of the best compound in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)