Increased collagen degradation around loosened total hip replacement implants

Objective. To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. Methods. The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients. Proteoglycans were extracted with 4M guanidinium chloride. Denatured collagen in the remaining matrix was solubilized with a-chymotrypsin. Nonsoluble matrix and supernatant fractions were acid hydrolyzed before measurement of hydroxyproline. The proportion of soluble (in vivo-degraded) collagen of the total sample collagen content was calculated. Proteinases were stained using the avidin-biotin-peroxidase complex method. Results. Collagen in the interface membrane from the implants was highly degraded (mean +/- SEM 20 +/- 3%) compared with that in the control synovial membranes (12 +/- 1%; P = 0.007). In controls, the degree of collagen degradation did not correlate with levels of matrix metalloproteinase 1 (MMP-1), MMP-13, or cathepsin K, although MMP-1 approached statistical significance. In interface membranes, the correlations were r = 0.88 (P = 0.002), r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP-1, MMP-13, and cathepsin K, respectively. Conclusion. In normal synovial membrane, collagen matrix remodeling may be mainly an intracellular process. In contrast, pathologic tissue destruction in the interface membrane from prosthetic hip joints is associated with a shift toward MMP-13 and cathepsin K, which become activated and overcome their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin Q. The highly significant correlation between collagen degradation and cathepsin K indicates an extracellular role of this acidic endoproteinase, consistent with previous observations concerning the acidity of the interface membrane.