Factors affecting the solubility of calcium pyrophosphate dihydrate crystals

The solubility of triclinic calcium pyrophosphate dihydrate (CPPD) crystals was measured under varying conditions using 45Ca-labeled crystals, expressing solubility as micromoles per liter of 45Ca in solution. In a 0.1-M Tris-HC1 buffer pH 7.4, the solubility of accurately sized CPPD crystals (37-20mum) was 60muM with maximal solubility being attained after about 8 h incubation at 37degreeC. Reduction in crystal size, decrease in pH, increase in ionic strength, Mg++, citrate, and albumin all increased solubility. The most marked effects on solubility occurred when changing the calcium concentration or by enzymatic hydrolysis of inoganic pyrophosphate to orthophosphate. It was found that decreasing the ionized calcium level below 5 mg/100 ml resulted in a progressive enhancement of solubility. The observed solubility-enhancing effects of albumin could be explained solely on its calcium-binding ability and thereby, altered ionized calcium level. Diffusible calcium in synovial fluid was only 40% of the total calcium concentration, which means most joint fluids are normally near the critical concentration of 5 mg/100 ml of ionized calcium, below which solubility is enhanced. During surgery, especially parathyroidectomy, calcium levels fall, favoring dissolution of CPPD crystals. We speculate that the slight decrease in crystal size during dissolution frees them from their cartilaginous mold, resulting in a dose-dependent inflammatory reaction as they are "shed" into the joint space. Crystal shedding may be reinforced by the modest fall in joint fluid pH accompanying the inflammatory response.