Bisphosphonate bone affinity as assessed by the inhibition of apatite dissolution and growth in vitro
Henneman, Zachary J
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At present, the bisphosphonate (BP) family of drugs is one of the most widely prescribed pharmaceutical tools for the treatment of osteoporosis; they are extremely effective inhibitors of bone resorption and find wide application in medicine. Important components in their ability to inhibit bone resorption are their affinity for calcium phosphate surfaces and their ability to target to bone mineral. This has been modeled in vitro through studies of BP effects on the dissolution and growth of a bone-like mineral, hydroxyapatite (HAP), which has been previously reported and continues to be studied. This work is directed at BP effects on carbonated hydroxyapatite (CAP), which is thought to be more relevant to human bone. In this thesis, the inhibitory effects of BPs on the dissolution and growth processes, at pH 5.50 and 7.40 respectively, were studied by a constant composition (CC) method at both physiological ionic strength and temperature, 0.15M and 37°C. First, the dissolution of CAP samples at varied relative supersaturation, σ, at pH 5.50 was explored to understand the effect carbonate has on the solubility of the mineral; second, the amount of carbonate (% by mass) incorporated into the lattice was explored to determine the effects carbonate has on the kinetics of dissolution; and third, the inhibitory effects of BPs, both concentration dependence and R 2 side-chain structure, were explored to determine potency. Lastly, the overall effect of BPs on the growth of HAP crystallites on CAP seed surfaces was investigated in order to simulate the remodeling of bone mineral and the effect these drugs have on that process. Knowledge gained from these studies goes towards the overall understanding of how the skeletal system is maintained through constant remodeling, as well as the effects of preventative maintenance in abnormal circumstances that are observed during periods of disease.