Bisphosphonates are analogues of pyrophosphate species. Two phosphonic acid groups are bonded to the carbon atom, forming the P-C-P backbone of the bisphosphonate. Several types of bisphosphonates have been developed during the past two decades. Bisphosphonates have clinical use in diagnostic and therapeutic applications in the treatment of various bone diseases and calcium metabolism. In our ab initio molecular orbital studies, one to three water molecules, dimethylphosphinic acid monoanions, dimethylphosphinothioic acid monoanions, and dianionic methylenebisphosphonates were bonded to the surface calcium of molecular modeled hydroxyapatite (HAP) crystal. To study additional bisphosphonate-calcium bonding, a model of the bisphosphonate-calcium-bisphosphonate complex was investigated in different conformations. All the molecular structures studied were fully optimized by a 3-21G((*)) basis set, and the molecular energies obtained were studied by means of model reactions.