Crystalline Calcium Alendronate Obtained by Octacalcium Phosphate Digestion: A New Chance for Local Treatment of Bone Loss Diseases?

摘要

The earliest studies on bisphosphonates (BPs) showed that these compounds could bind to hydroxyapatite (HA) crystals and inhibit crystal growth and dissolution in a similar fashion to pyrophosphates. Following a number of further investigations, BPs are at present recognized as potent inhibitors of osteoclast activity and widely used clinically for the treatment of diseases associated with conditions of bone loss, such as osteoporosis, Paget's disease and osteolytic tumors. BPs are indeed analogues of naturally occurring pyrophosphate in which the oxygen atom is replaced by a carbon atom giving a P-C-P bridge resistant to both chemical and enzymatic hydrolysis. The α-carbon typically carries two separate substituents, R_1 and R_2, which account for the BP mineral affinity and pharmacological activity. BPs display also antiangiogenesis properties and nitrogen containing BPs, N-BPs, exert several antitumor effects. Recently described adverse side effects of bisphosphonate therapy, including osteonecrosis of the jaw, stimulated a number of studies aimed to develop strategies for local administration of bisphosphonates. In particular, the possibility to use calcium phosphates as delivery agents for BPs has been explored.