EVEN LOW-GRADE SYNOVITIS SIGNIFICANTLY ACCELERATES THE CLEARANCE OF PROTEIN FROM THE CANINE KNEE - IMPLICATIONS FOR MEASUREMENT OF SYNOVIAL-FLUID MARKERS OF OSTEOARTHRITIS

Objective. In recent studies, the synovial fluid concentration of mole cules 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 pr esent in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial flu id, Methods, I-131-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 surf ace radioactivity were used to calculate the volume of distribution (V -d) and clearance of RISA, One week later, synovitis was induced in th e 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. Res ults, Intraarticular injection of 500 mu g of CPPD crystals produced i ntense synovitis, with a mean synovial fluid white blood cell (WBC) co unt of 43,200 cells/mm(3), and values for RISA V-d and RISA clearance (36.5 ml and 33.7 mu l/minute) were much higher than those for saline- injected control knees (2.7 ml and 1.5 mu l/minute, respectively), Inj ection of 0.5 mu g of CPPD also produced marked synovitis and values f or V-d and RISA clearance that were 2-3-fold greater than those in the contralateral knee, The low-grade synovitis produced by only 0.05 mu g of CPPD, which resulted in synovial fluid WBC counts as low as 1,000 -2,000 cells/ mm(3), was accompanied by increases in the clearance and V-d of RISA to levels similar to 40% and similar to 80% higher, respe ctively, than those for the contralateral knee, Conclusion, Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint, Synovitis is a significant variable which mu st be considered in studies of putative chondroprotective drugs if con clusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a ''marker'' protein.