Even low‐grade synovitis significantly accelerates the clearance of protein from the canine knee: implications for measurement of synovial fluid “markers” of osteoarthritis

Abstract

In recent studies, the synovial fluid concentration of molecules derived from the extracellular matrix of articular cartilage has been used to deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA) joints. Because low-grade synovitis is often present in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial fluid. 131I-labeled albumin (RISA) was injected into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial fluid aspirated 7 hours after the injection and serial measurements of surface radioactivity were used to calculate the volume of distribution (Vd) and clearance of RISA. One week later, synovitis was induced in the contralateral knee by intraarticular injection of various quantities of calcium pyrophosphate dihydrate (CPPD) crystals, after which RISA was injected into that joint and these measurements were repeated. Intraarticular injection of 500 micrograms of CPPD crystals produced intense synovitis, with a mean synovial fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd and RISA clearance (36.5 ml and 33.7 microliters/minute) were much higher than those for saline-injected control knees (2.7 ml and 1.5 microliters/minute, respectively). Injection of 0.5 microgram of CPPD also produced marked synovitis and values for Vd and RISA clearance that were 2-3-fold greater than those in the contralateral knee. The low-grade synovitis produced by only 0.05 microgram of CPPD, which resulted in synovial fluid WBC counts as low as 1,000-2,000 cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels approximately 40% and approximately 80% higher, respectively, than those for the contralateral knee. Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint. Synovitis is a significant variable which must be considered in studies of putative chondroprotective drugs if conclusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a "marker" protein.