Bisphosphonates (BPs) are extensively used drugs for the prevention and treatment of bone mineral resorption including osteoporosis, Paget’s disease, tumor induced osteolysis and hypercalcemia. Recently, BPs have also been found to have anti-cancer property via stimulate γδT cells of the immune system. The pharmaceutical efficacy of BPs, in particular the anti-resorptive potency of nitrogen-containing bisphosphonates (NBPs) is determined by two factors: their affinity to target bone minerals, and ability to inhibit the enzyme farnesyl pyrophosphate synthase (FPPS) after accumulation to the osetoclastic cells. The binding of bisphosphonates (BPs) to bone mineral is an essential step leading to their biological effects. The typical structural motif of BPs is two phosphonic acids, P-C-P, and in NBPs a nitrogen-containing side chain, and a -OH group attached to the same carbon. The aim of this report provides an overview of the study of physicochemical property of BPs.

Significant differences were seen in mineral binding among the clinically-relevant BPs. The rank of mineral affinity of BPs is compared with their inhibitive potential to the enzyme of FPPS. The physicochemical property of BPs may shed light in their application for the prevention and treatment of cancer metastasis in bone. However, further study using in vivo and 3D in vitro cancer metastasis models is warranted to explore the underlying molecular mechanism.