PURPOSE: This study evaluated the expression level of Receptor Activator of NF-kappaB Ligand (RANKL), Osteoprotegerin (OPG)and other pro-inflammatory cytokines in the osteoarthritic and periprosthetic joint fluid in order to characterize the role of these regulatory proteins in periprosthetic osteolysis. MATERIALS AND METHODS: Joint fluid specimens taken from 47 patients undergoing hip or knee reconstructive surgery were analyzed by enzyme-linked immunoassay (ELISA)in order to determine the relative protein expression level of RANKL, OPG, IL-1beta, IL-6 and TNF-alpha. The fluid from joints with osteoarthritis (15 cases, Group I), implants revised without associated osteolysis (15 cases, Group II)and failed implants with radiographically moderate to severe osteolysis (17 cases, Group III) were compared. The fluids from all cases with implants (Group II and III) was combined (Group IV)and compared with the osteoarthritic joint fluids. RESULTS: RANKL was present in all the fluids at similar concentrations. The OPG levels were significantly lower (2.2-3.9 fold)in Groups II and III than in Group I (p<0.0001). The IL-1beta concentration was significantly higher in Groups II, III and IV and with Group III being the highest (12.1 fold)(p<0.0001). The IL-6 expression level was significantly higher in Group III (2.0 fold)than in Groups I and II (p<0.0001). The TNF-alpha levels were 2.0 times higher in Group III and significantly higher in all implant cases (Group IV)are analyzed (p=0.03). CONCLUSION: Permissive RANKL protein expression coupled with suppressed OPG levels and enhanced osteoclastogenic cytokine expression results in periprosthetic osteolysis.
Cytokines ; Hip ; Humans ; Immunoassay ; Interleukin-6 ; Joints* ; Knee ; Osteoarthritis ; Osteolysis* ; Osteoprotegerin ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; Tumor Necrosis Factor-alpha

PURPOSE: Wear particle induced osteolysis is a serious complication in total joint arthroplasty. The purpose of this study was to compare the preventive and mitigative effects of alendronate on particle induced osteolysis among particles using mouse calvarial model. MATERIALS AND METHODS: Seventy-two mice were randomized into sham group, Ti6Al4V group, CoCr- Mo group and Ultra High Molecular Weight Polyethylene (UHMWPE) group according to the particles treated to the calvarial tissues. Each group was divided into control subgroup which received no alendronate, preventive subgroup which received alendronate for 4 weeks after particle distribution and therapeutic subgroup which received alendronate for 3 weeks after 1 week delay from particle distribution. We evaluated the effects quantitatively using histomorphometry. Number of osteoclast, fibrous thickness, eroded bone surface area, bone thickness and bone volume were measured and compared. RESULTS: Alendronate showed significant preventive and mitigative effects on osteolysis induced by Ti6Al4V particles and showed significant preventive and somewhat less mitigative effect on osteolysis by CoCrMo particles. On UHMWPE particles, alendronate showed no preventive and mitigative effects. CONCLUSION: Alendronate may be useful in preventing osteolysis induced by metal particles but had no effect on ostelysis induced by UHMWPE particles.
Alendronate* ; Animals ; Arthroplasty ; Cytochrome P-450 CYP1A1 ; Joints ; Mice* ; Molecular Weight ; Osteoclasts ; Osteolysis* ; Polyethylene