The measurement of an off-rate for alendronate demonstrated that it does not irreversibly bind to the bone surface. Independent measurements of the on-rate (69/M/min) and the off-rate (0.033/min) for binding to human bone yielded a K d of 470 μM, which was about 4-fold higher than the observed K d of 110 μM and about 1000-fold higher than that seen with hydroxyapatite. For example, a more recent study demonstrated that the more soluble carbonated apatite gave a similar rank order of affinities, but with somewhat less variation ( Henneman et al., 2008). The difference with the reported affinity for pure hydroxyapatite (0.34 μM) is potentially attributable to differences in methodology and/or the composition of the binding surface (hydroxyapatite versus bone). The direct binding affinity of alendronate for human bone was measured by Scatchard analysis, with a measured K d of 110 μM ( Leu et al., 2006). Rogers, in Principles of Bone Biology (Third Edition), 2008 Binding to Human Boneīinding constants representing bisphosphonate affinity for human bone have been calculated by using several different methodologies. In contrast, half-life of alfacalcidol as a prodrug of 1,25(OH) 2D 3 is 47 h, and that of eldecalcitol is 53 h, which enables both of them to be used under once-a-day dosing.Īnke J. Because the half-life of 1,25(OH) 2D 3 is 28 h, twice-a-day dosing is used for osteoporosis treatment. The sustainable exposure because of its long half-life may provide eldecalcitol with strong pharmacological effect in osteoporosis treatment. Multifunctional and potent roles of the 3-hydroxypropoxy group provide eldecalcitol’s benefit in osteoporosis treatment. Through the three H-bonds in the 3-hydroxypropyloxy group, eldecalcitol tightly binds to DBP and exhibits the high affinity to DBP and the long half-life (53 h) in serum. The possible H-bonds in the 3-hydroxypropyloxy group are indicated by dotted lines. Binding models of vitamin D-binding protein (DBP) with (A) calcitriol and (B) eldecalcitol.īoth ligands were docked into the DBP X-ray structure (PDB: 1J78) manually by using Discovery Studio 3.5. (2) The sum of the strengths of multiple binding sites between an antibody and an antigen, which increased stability of the linkage, as measured by the association or affinity constant.Figure 93.1. (1) A thermodynamic expression of the strength of the interaction between a single antigen binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. (3) The reciprocal of the dissociation constant.ĭevelopmental biology The degree to which one substance is attracted to another. (2) The strength of noncovalent binds between two substances, as measured by the dissociation constant of the complex. (1) The intensity of a force that binds atoms in molecules the tendency of substances to combine by a chemical reaction. (2) A special attraction for a specific element, organ, or structure. The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company.