Biochemical markers of particle induced osteolysis in C57BL/6 mice Increased bone turnover as reflected by biochemical markers in patients with potentially unstable fixation of the tibial component Systemic cross-linked N-terminal telopeptide and procollagen I C-terminal extension peptide as markers of bone turnover after total hip arthroplasty. Interleukin-6 in the blood of patients with total hip arthroplasty without loosening. Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study. Serum levels of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand as markers of periprosthetic osteolysis.
Abstract Background : Micro-structural changes associated with ultra high molecular weight polyethylene particle ( UHMWPE ) induced osteolysis , the most frequent cause of aseptic loosening , have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography . However , little is known regarding the serological changes that occur during this process . Methods : Serological parameters for bone metabolism [ calcium , phosphate , osteocalcin ( OCN ) , deoxypyridinoline (DPD)/creatinine , alkaline phosphatase , osteoprotegerin and receptor activator of nuclear factor-κB ] were analyzed in this animal model for particle induced osteolysis . Ten C57BL/6 mice were divided at r and om into sham operated and UHM-WPE implanted groups . Blood and urine sample s were collected prior to and at 14 days after surgery . Results : Implantation of UHMWPE lead to a significant decrease in bone volume ( p=0.027 ) . Both groups ( sham/UHMWPE ) showed a significant increase in calcium ( p=0.004/p=0.027 ) and phosphate ( p=0.001/p=0.001 ) , without correlation to particle implantation . Significantly higher concentrations of DPD/creatinine ( p=0.034 ) and OCN ( p=0.022 ) were found after implantation of UHM-WPE . In addition , parameters could not be correlated to particle induced osteolysis . Conclusions : DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model . Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening . Clin Chem Lab Med 2010;48:1641–6 Introduction Whether biochemical markers of bone metabolism can be used in assessing the conditions of implant fixation is unknown . In this study , the serum levels of three bone markers were measured prospect ively in patients undergoing total knee arthroplasty ( TKA ) to determine if patients with different fixation conditions of the tibial component showed any differences in the levels of the markers . Material s and methods The fixation of the tibial component in 40 knees ( 40 patients , 14 male and 26 female , average age 71 years ) was assessed by radiostereometric analysis ( RSA ) , and based upon the pattern of migration , implants with stable fixation ( n=25 ) and potentially unstable fixation ( n=15 ) were identified . Serum levels of carboxyterminal propeptide of type I procollagen ( PICP ) , osteocalcin ( OC ) and cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) were assessed and compared between the two fixation groups . Blood sample s were obtained preoperatively ( baseline ) and repeated postoperatively at 1 week , 3 , 6 , 12 , and 24 months . Results The baseline levels of the markers were statistically the same ( p>0.05 ) between the two fixation groups . Postoperatively , ICTP levels in the unstable group were significantly higher than in the stable group from 6 to 24 months ( p=0.02 ) . Levels of OC in the unstable group were higher at 12 and 24 months compared with the stable group , reaching statistical significance only at 12 months ( p=0.03 ) . No difference in the levels of PICP was found between the two groups . Conclusion The findings indicate a more active bone turnover probably at the bone-cement/implant interface in knees with potentially unstable fixation . It reveals the potential value for biochemical markers in monitoring implant fixation and aseptic loosening and suggests a possibility for improving implant fixation by drugs which inhibit osteolysis There is no diagnostic , non-invasive method for the early detection of loosening after total hip arthroplasty . In a pilot study , we have analysed two serum markers of bone remodelling , procollagen I C-terminal extension peptide ( PICP ) and cross-linked N-terminal telopeptide ( NTx ) , as well as the diagnostic performance of NTx for the assessment of osteolysis . We recruited 21 patients with loosening ( group I ) , 18 with a well-fixed prosthesis ( group II ) and 17 at the time of primary arthroplasty for osteoarthritis ( OA ) ( group III ) . Internal normal reference ranges were obtained from 30 healthy subjects ( group IV ) . The serum PICP level was found to be significantly lower in patients with OA and those with loosening , when compared with those with stable implants , while the NTx level was significantly increased only in the group with loosening , suggesting that collagen degradation depended on the altered bone turnover induced by the implant . This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects . A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations . The NTx level could be used to indicate stability of the implant . However , further prospect i ve , larger studies are necessary Patients with total hip arthroplasty were screened for the presence of proinflammatory cytokines in the systemic circulation . Only increased levels of interleukin-6 were detected in patients having had total hip arthroplasty more than 10 years ago . These increased levels of interleukin-6 were associated with a decrease in bone mineral density associated with polyethylene wear and with radiologic osteolysis in some patients . These abnormalities were not found in control subjects without total hip arthroplasty or in patients who had a prosthesis in place for less than 6 years . The elevation in interleukin-6 levels found in patients with the oldest prostheses could constitute a marker for periprosthetic osteolysis In a cohort study , the role of the active tartrate-resistant acid phosphatase ( TRACP 5b ) , a marker of bone-resorbing osteoclasts , for the assessment of loosening after total hip arthroplasty ( THA ) , was analyzed , as well as its correlation with osteolysis and multinucleated cell appearance in the retrievals . Eighty THA patients , who went consecutively to the orthopedic department , were asked to participate , and 54 accepted and were enrolled in the study . Finally , 46 subjects were analyzed , clinical -radiographic evaluation was considered the gold st and ard , serum TRACP 5b was blindly measured , and a cut-off was obtained , by performing a ROC Curve . Based on the gold st and ard , patients were split by 19 stable and 27 loosened subjects , and results were matched . TRACP 5b was significantly higher in loosened patients than in stable ones ( p < 0.001 ) . A good specificity ( 89.5 % ) , positive predictive value ( 90.0 % ) , and likelihood ratio ( 6.33 ) were calculated , that provided strong evidence of loosening with TRACP 5b levels higher than the cut-off . Moreover , TRACP 5b and osteolysis ( Fisher 's exact test , p = 0.03 ) were found significantly correlated . TRACP 5b has been proven a reliable marker , specifically related to resorbing-multinucleated cells , to ascertain late loosening in THA , and could support st and ard procedures , if confirmed by performing prospect i ve studies BACKGROUND Previous studies have suggested that the balance between receptor activator of nuclear factor-kappaB lig and ( RANKL ) and its decoy-receptor osteoprotegerin ( OPG ) in local tissue seems to play a crucial role in the loosening of the total hip replacement . The aim of this study was to evaluate whether the circulating levels of OPG and RANKL , as well as their ratio , could be different in patients with aseptic loosening compared with patients with stable implants . METHODS One hundred and twenty-eight subjects were recruited . They included thirty-nine patients with osteoarthritis who had not yet undergone total hip arthroplasty , thirty-three patients who had undergone total hip arthroplasty and had clinical ly and radiographically stable implants , thirty-six patients with aseptic loosening of total hip arthroplasty components , and twenty healthy volunteers .  Serum levels of OPG and RANKL  were measured with use of an immunoenzymatic method , and in each individual the  OPG-to-RANKL ratio  was calculated . RESULTS In every group , a significant correlation was detected between OPG concentration and age ( r = 0.58 , p < 0.0001 ) , especially in individuals older than fifty years , while gender and underlying disease were not found to influence serum levels of the tested parameters . In comparison with the levels in healthy donors and patients with a stable total hip replacement , the serum levels of OPG  were increased in the patients who had not yet had an arthroplasty , those with aseptic loosening of a total hip replacement , and those with a cemented total hip replacement . Moreover , the  OPG serum level provided good diagnostic accuracy in detecting the implant failure . A correlation was found between the sum of the osteolytic areas seen radiographically around the femoral stem and the RANKL level ( r = 0.38 , p = 0.02 ) and the  OPG-to-RANKL ratio ( r = -0.29 , p = 0.04 ) . CONCLUSIONS An increase in  OPG levels may reflect a protective mechanism of the skeleton to compensate for the osteolytic activity that occurs in severe osteoarthritis and in aseptic loosening . Prospect i ve studies are needed to determine whether serum OPG levels could be used as markers for monitoring the stability of the implant , as well as for predicting aseptic loosening . LEVEL OF EVIDENCE Diagnostic study , Level III . See Instructions to Authors for a complete description of levels of evidence
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