[Bisphosphonates, their mechanism of action and properties useful in the therapy of metabolic bone diseases].

Bisphosphonates are a group of chemical substances which have been used in medicine for thirty years in the treatment of skeletal diseases and disorders of calcium metabolism. Bisphosphonates are derived from pyrophosphate by substitution of an O atom for a C atom. This structure makes possible a number of variants by changing the side-chains of the C atom. The basic P-C-P bond is very thermostabile and completely resistant to enzymatic hydrolysis. The basic biological property of bisphosphonates is inhibition of bone resorption but has not been completely elucidated so far. The prerequisite is the inhibitory action of bisphosphonates on osteoclast activity. The latter are inhibited only when they are in contact with bone surfaces which contain bisphosphonates. Another possible mechanism of action of bisphosphonates is their action on osteoblasts: osteoblasts produce local growth factors which inhibit osteoclasts and thus osteoresorption is inhibited. So far it is not exactly known whether the direct effect on osteoclasts, the indirect effect via osteoblasts or a combination of both are the most important effect of bisphosphonates on the resorption of bone.