Hydroxyapatite bone mineral surfaces

Actions. These compounds are effective calcium chelators that rapidly target exposed bone mineral surfaces in vivo, where they can be released by bone-resorbing osteoclasts, resulting in inhibition of osteoclast function and osteoclast apoptosis. The bisphosphonates (alendronate, clodronate, etidronate, pamidronate, risedronate, tiludronate and zoledronate) inhibit the activation and function of osteoclasts and possibly directly stimulate formation of bone by the osteoblasts. They also bind strongly to hydroxyapatite crystals and, in high doses, can inhibit the mineralisation of bone. The doses at which effects on mineralisation occur are not related to antiresorptive efficacy. There is wide variation between these compoimds in terms of their capacity to inhibit... 

The previously proposed uptake models were mathematical assumptions and had no physical or chemical basis. Millard and Hedges, on the other hand, considered the chemistry of bone-uranium interactions. With the D-A model, they proposed that U was diffusing into bone as uranyl complexes, and adsorbing to the large surface area presented by the bone mineral hydroxyapatite (Millard and Hedges 1996). Laboratory experiments showed a partition coefficient between uranyl and hydroxyapatite under oxic conditions of 10" -10, demonstrating U uptake in the U state without the need for reduction by protein decay products as proposed by Rae and Ivanovich (1986). 

Because of the importance of the surface chemistry of bone mineral in physiological systems, we have undertaken a series of gas adsorption studies on hydroxyapatite in the form of anorganic bone. In a recent publication from this laboratory (4) results of calorimetric studies of the adsorption of water and methanol vapors on bone mineral and on synthetic hydroxyapatite were reported. The adsorption potential for nitrogen on dehydrated hydroxyapatite, whether from bone or from synthetic sources, was rather profoundly altered by the addition to the surface of chemisorbed methanol or water prior to the adsorption of nitrogen at —195° C. This effect was reflected in the specific surface areas, in the BET C values, and in the resultant values of Ex — EL (net heats of adsorption) as shown in Table I of the above paper. 

Pamidronate disodium is a bisphosphonate which binds irreversibly to hydroxyapatite in bone. It is a strong inhibitor of bone resorption, reducing osteoclast or osteoclast precursor activity. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts. 

Hydroxyapaite, the mineral constituent of bone, is appHed to the surfaces of many dental implants for the purpose of increasing initial bone growth. Some iavestigators beHeve that an added benefit is that the hydroxyapatite shields the bone from the metal. However, titanium and its aHoy, Ti-6A1-4V, are biocompatible and have anchored successfuHy as dental implants without the hydroxyapatite coating. 

Bisphosphonates. Bisphosphonates are synthetic compounds designed to function as mimics of pyrophosphate, in which the oxygen atom in P-O-P is replaced with a carbon atom, creating a non-hydrolyzable backbone structure. The bisphosphonates selectively bind to the hydroxyapatite portion of the bone, decreasing the number of sites along the bone surface at which osteoclast-mediated bone resorption can occur. This permits the osteoblasts to lay down well-mineralized new bone without competition from osteoclasts. Clinically employed bisphosphonates include etidronate (8.109), tilu-dronate (8.110), risedronate (8.111), alendronate (8.112), and pamidronate (8.113). 

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