Disodium Pamidronate Therapy of Paget’s Disease
Several bisphosphonate analogues are currently in use for the treatment of bone disorders, with the best known being etidronate disodium, disodium clodronate (Cl2 MDP), and disodium pamidronate, also known as disodium APD.1 APD is chemically disodium (3-amino-1-hydroxy-propylidene)-1, 1-bisphosphonate. The inhibitory action of the bisphosphonates on bone resorption requires prior chemisorption to the calcified bone matrix,2–4 which is achieved through two phosphonate groups connected by a central carbon atom, the P-C-P bond, which all the bisphosphonates have in common. The two phosphonates form complexes with calcium salts and with the hydroxyapatite crystals embedded in bone matrix.1 Their presence on crystal surfaces changes the energy distribution on these surfaces and the chemical composition of the mineral, according to the nature of the nonbisphosphonate groups of the bisphosphonate, so that some of them make crystals grow more slowly and also dissolve more slowly. In addition, several bisphosphonates alter biologic processes taking place at the surface of bone crystals. Some may inhibit bone resorption by direct inhibition of bone-resorbing cells, others by impairing accession to bone of these cells. The high affinity of bisphosphonates for Bone Mineral is exploited in scintigraphy, in which bisphosphonates bound to radioactive tracers localize to bony areas having increased turnover. Phosphonate bonds are not hydrolyzable by alkaline phosphatases or pyrophosphatases. This, together with their strong chemisorption to Bone Mineral, is responsible for a long half-life once deposited there.
KeywordsOsteoclast Precursor Serum Alkaline Phosphatase Level Central Carbon Atom Serum Alkaline Phosphatase Activity Etidronate Disodium
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