%0 Journal Article
%T The role of bisphosphonates in breast cancer: Development of bisphosphonates
%A Herbert Fleisch
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr414
%X The bisphosphonates, in the past erroneously called diphosphonates, have been known to chemists since the middle of the 19th century, the first synthesis dating back to 1865 in Germany [1]. Their use was industrial (mainly in the textile, fertilizer and oil industries) and, because of their property of inhibiting calcium carbonate precipitation, as preventors of scaling. Our knowledge of the biological characteristics of bisphosphonates dates back 30 years, the first report about them, actually by the present author's group, having been presented in 1968 [2]. The concept was derived from earlier studies in our laboratory on inorganic pyrophosphate [3], in which it was found that plasma and urine contained compounds inhibiting calcium phosphate precipitation in vitro and it was found that part of this activity was due to inorganic pyrophosphate, a substance that had not been described previously in these fluids. We then found that pyrophosphate also inhibited calcium phosphate dissolution in vitro. In vivo, this compound prevented ectopic calcification but had no effect on normal mineralization and on bone resorption, possibly because it was destroyed locally by phosphatases. This prompted us to look for analogs of pyrophosphate that were not destroyed enzymatically. The bisphosphonates fulfilled these conditions [4,5].Bisphosphonates are compounds characterized by two C¨CP bonds. If the two bonds are located on the same carbon atom the compounds are called geminal bisphosphonates (although usually just bisphosphonates), and they are analogs of pyrophosphate that contain an oxygen atom instead of a carbon atom (Figs 1 and 2 show two bisphosphonates used in tumor bone disease).The P¨CC¨CP structure allows a great number of possible variations, mostly by changing the two lateral chains on the carbon. Small changes in the structure of the bisphosphonates can lead to extensive alterations in their physicochemical, biological, therapeutic, and toxicological characteristics.
%K bisphosphonates
%K bone
%K bone resorption
%K calcification
%K inhibitors
%U http://breast-cancer-research.com/content/4/1/30