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Abstract

The physicochemical effects of many of the bisphosphonates are very similar to those of pyrophosphate. Thus, they inhibit the formation, delay the aggregation, and slow down the dissolution of calcium phosphate crystals. All these effects are related to the marked affinity of these compounds for solid-phase calcium phosphate, on the surface of which they bind strongly. This property is of great importance, because it is the basis for the use of these compounds as skeletal markers in nuclear medicine and the basis for their selective localization in bone when used as drugs. Bisphosphonates also inhibit the formation and the aggregation of calcium oxalate crystals. The main effect of the pharmacologically active bisphosphonates is to inhibit bone resorption. These compounds proved to be extremely powerful inhibitors of resorption when tested in a variety of conditions, both in vitro and in vivo. Another interesting finding is that several bisphosphonates, including clodronate, risedronate, and zoledronate, inhibit local bone and cartilage resorption, preserve the joint architecture, and decrease the inflammatory reaction in various types of experimental arthritis, such as that induced by Freund's adjuvant or by carrageenan. This effect is especially pronounced when the bisphosphonates are encapsulated in liposomes. Very low concentrations of bisphosphonates were found to increase colony formation, nodule formation, mineralization, and osteocalcin synthesis in bone cell cultures in vitro.