Clearance of calcium pyrophosphate dihydrate crystals in vivo

Abstract

Synthetic triclinic calcium pyrophosphate dihydrate crystals were uniformly trace-labeled with Ytterbium-169 ('Tb), a pure gamma-emitting isotope with a halflife of 31 days. The solubility of the labeled crystals was similar to that of cold synthetic crystals. The clearance rate of labeled sterile crystals, sieved to obtain the desired size, was determined after injection of microgram quantities into 4 arthritic human and 3 normal adult rabbit joints and corrected by the observed rate of clearance of free ' T b . The derived rate constants were then used to calculate the time required for half of the injected dose of CPPD to be cleared from the joint. Crystal clearance was found in all instances. Crystal removal from normal rabbit joints was much more rapid than from the much larger human arthritic joints and was inversely proportional to the size of the crystals injected.Postmortem data indicate that the prevalence of calcium pyrophosphate dihydrate (CPPD) crystal deposition in human knee joint cartilage is about 5% (1,2). Such deposition may be accompanied by inflammatory arthritis and progressive degeneration of cartilage in afflicted joints. The acute attacks of arthritis have been called "pseudogout," since they are clinically similar to, and often mistaken for, acute gouty arthritis caused by microcrystalline monosodium urate (MSU) (3); MSU crystals are in equilibrium with urate in solution in extracellular fluids (4), and therapy designed to reduce and maintain normal urate concentrations results in gradual dissolution of tophaceous masses. Estimation of the rate of CPPD crystal dissolution in arthritic human and normal rabbit joints is the subject of this report. This and subsequent work may provide a rational basis for therapeutic attempts to remove crystals from affected joints MATERIALS AND METHODSPreparation and labeling of crystals. Triclinic CPPD were prepared by the following method: All reagents were prepared in doubly deionized, glass-distilled, charcoal-filtered water; 65 mi of water were heated in a 200 ml beaker in a water bath to 6OoC f 2' and a small Teflon stir bar was added. Concentrated HC1,0.45 ml and 0.2 ml glacial acetic acid were added while slowly stirring; 375 mg Ca (C2H302)2-H20 were added to 12.5 ml water in a 25 ml beaker and held in the water bath at 6OOC. An additional 375 mg Ca (CZH302)2-H20 were then dissolved in the larger beaker. (Both salts were a kind gift of J. R. Lehr, National Fertilizer Center, Muscle Shoals, Alabama.) The rate of stir was increased and 1.25 gm CaH,P20, were added rapidly to the larger beaker. A stopwatch was started. After 60 seconds, the rate of stirring was slowed to keep the solids just suspended. Radionuclide was then added. Ytterbium-I69 (I69yb), 2 to 4 mCi (Amersham Searle), was used; the 169Yb content of various batches varied from 1.4 to 7.4 pg per mCi. The suspension was stirred slowly for 4 minutes, at which time the dissolved Ca (C&02)2 -H 2 0 in the small beaker was added during 15 seconds of vigorous stirring. Stirring was then disconti...

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