Determination of Solubility and Calcium Ion Stability Constants of a Phosphonoalkylphosphinate (PAP) and Bisphosphonates (BPs) Such as EHDP, Risedronate, Alendronate, 3-pic AMBP, and 3-pic AMPMP

Abstract

The first member of the bis- or diphosphonate (BP) analogous was first synthesized in 1897.¹ Over six decades later Blaser and Worms patented the first use of a BP², Ethylidene-1, 1-hydroxy bisphosphonic acid (EHDP), for the soluble complexation of metal ions, primarily calcium and magnesium. Since that time many interesting structural variants of the BPs have been synthesized which have found extensive use in chemical, medical, and dental application. The first dental use of a BP was for the inhibition or blockage of calculus or tartar deposition. The principle involved was the adsorption of EHDP on the tooth surface and to any nuclei of calculus that might form on the tooth surface. The concentrations of topical solution and dentifrice were such that EHDP saturated the calcium phosphate crystal’s growing surfaces thus, inhibiting deposition and accumulation of supragingival calculus. The first medical use of a BP was based on a principle similar to that of calculus inhibition involving the oral dosing of EHDP to a sixteen month old child with ossifying deposition (myositis ossificans progressiva). The principle again was to produce a saturating adsorption of BP on the sites of calcium phosphate deposition in the muscle tissues and so block the debilitating effects of the unwanted accretion. In a somewhat similar medical application for heterotopic ossification, etidronate has been used successfully for the inhibition of calcification of soft tissue resulting from hip replacement or spinal chord injury. Again the principle is the same, sites of rapidly forming calcium phosphate in muscle tissue can be saturated by oral administration of etidronate and blocked from further deposition which destroys muscle tissue function.