(735a) Additive Effects on the Growth and Polymorph Transformations of Calcium Pyrophosphate Crystals

Calcium pyrophosphate deposition disease (pseudogout) is a rheumatologic condition caused by the formation of calcium pyrophosphate (CaPP) crystals in joints.  Nearly half of people over the age of 80 may develop CaPP crystals in their joints.[1] Yet, the mechanism by which CaPP crystals form in the joints is not well established. Furthermore, there is currently no known treatment to inhibit the growth of CaPP crystals. Mechanistic understanding of how additives effect nucleation, growth, and polymorph selection of CaPP crystals is necessary to develop additives that inhibit their formation or growth.

We use atomistic modeling to study additive effects on the CaPP monoclinic dihydrate crystal structure found during in vivo studies of human joints.[2] To properly model the effects of additives, we developed a new force field using the CHARMM force field potential as a starting point. The force field accurately reproduces the crystal structures of the monoclinic dihydrate, and a tetrahydrate form of CaPP.

Simple metal salts have been shown experimentally to influence crystal growth and polymorph transformations of CaPP crystals in aqueous solution. In order to better understand the effects of salts on CaPP crystal growth and polymorph transformations, we calculate binding free energies between metal cations and CaPP crystal faces.

References

[1] Guerne, P. A., and R. Terkeltaub, “Calcium pyrophosphate dihydrate crystal deposition: epidemiology, clinical features, diagnosis, and treatment,” Chapter 21 in Terkeltaub, R., ed., “Gout and Other Crystal Deposition Arthropathies”, Elsevier Heath Sciences, Philadelphia, PA (2012).

[2] McCarthy, D. J., N. N. Kohn, and J. S. Faires, "The Significance of Calcium Pyrophosphate Crystals in the Synovial Fluid of Arthritic Patients: The "Pseudogout Syndrome". II. Identification of crystals,” Ann. Intern. Med., 56, 838-845, (1962).