Abstract:Particle-induced osteolysis is caused by an imbalance in bone resorption and formation, often leading to loss of implant fixation. Bone remodeling biomarkers may be useful for identification of osteolysis and studying pathogenesis, but interpretation of biomarker data could be confounded if local osteolysis engenders systemic bone remodeling. Our goal was to determine if remote bone remodeling contributes to biomarker levels. Serum concentrations of eight biomarkers and bone remodeling rates at local (femur), … Show more
“…Indeed, the one longitudinal study included in this review showed that the bone resorption marker, CTX-1, was elevated early in patients undergoing TKA suspected to have loosened implants [17] and we recently also found that this marker was elevated early in a rat model [27]. A major challenge in longitudinal studies in patients is stratification into aseptic loosening/osteolysis and control groups, which can only occur long after initiation of the study because of the normal etiology of the disease.…”
Section: Discussionmentioning
confidence: 97%
“…A second limitation is that we did not include animal studies in which biomarkers of aseptic loosening/osteolysis were studied [14,18,21,27] because only two of these studies included stable and loosened implants [18,27]. These two studies showed dramatic increases in serum CTX-1, OPG, cathepsin K, and PINP and depression of serum OC.…”
Background Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/ or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment. Questions/purposes We sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty. Methods We performed a systematic review using MED-LINE and EMBASE databases, covering the period through December 2013, and identified 1050 articles. We restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. We chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. We used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or periimplant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these two patient populations involving 35 different biomarkers. Results Diagnostic accuracy was assessed in nine of the 90 comparisons with the highest accuracy found for tartrateresistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of [ 0.80 was also found for crosslinked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-a and interleukin-1b, were found to differ in the affected and control groups in\30% of the comparisons. Thirty of the 35 biomarkers were studied in four or fewer separate comparisons with nearly half of the biomarkers (17) studied in only one comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only one prospective study. Conclusions Currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.
“…Indeed, the one longitudinal study included in this review showed that the bone resorption marker, CTX-1, was elevated early in patients undergoing TKA suspected to have loosened implants [17] and we recently also found that this marker was elevated early in a rat model [27]. A major challenge in longitudinal studies in patients is stratification into aseptic loosening/osteolysis and control groups, which can only occur long after initiation of the study because of the normal etiology of the disease.…”
Section: Discussionmentioning
confidence: 97%
“…A second limitation is that we did not include animal studies in which biomarkers of aseptic loosening/osteolysis were studied [14,18,21,27] because only two of these studies included stable and loosened implants [18,27]. These two studies showed dramatic increases in serum CTX-1, OPG, cathepsin K, and PINP and depression of serum OC.…”
Background Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/ or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment. Questions/purposes We sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty. Methods We performed a systematic review using MED-LINE and EMBASE databases, covering the period through December 2013, and identified 1050 articles. We restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. We chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. We used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or periimplant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these two patient populations involving 35 different biomarkers. Results Diagnostic accuracy was assessed in nine of the 90 comparisons with the highest accuracy found for tartrateresistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of [ 0.80 was also found for crosslinked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-a and interleukin-1b, were found to differ in the affected and control groups in\30% of the comparisons. Thirty of the 35 biomarkers were studied in four or fewer separate comparisons with nearly half of the biomarkers (17) studied in only one comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only one prospective study. Conclusions Currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.
“…Prior to storage at -80°C, blood was collected during euthanasia through the common iliac artery and centrifuged to separate serum at 2,000 rpm (425xg) for 5 min at 4°C as described previously [27, 28]. Serum OCN and VEGF levels were analyzed by using rabbit-specific enzyme-linked immunosorbent assay kits (Bioleaf Biotech, Shanghai, China) according to the manufacturer's protocol.…”
Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1–34] (PTH[1–34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.
“…4,17,20,21,37,38 To assess the reproducibility of the model, we re-analyzed outcome data from the mouse marrow ablation model and the rat implant fixation model in which the animal strain, age, sex and experimental end points were comparable. Both mouse studies included females from FVB/NJ and BALB/cJ strains of the same age (10-11 weeks) with the same end point (bone volume/tissue volume, BV/TV) at 7 days post-marrow ablation.…”
Section: Reproducibility Of Surgery Outcomesmentioning
confidence: 99%
“…Blood is then centrifuged to separate the serum from blood solids and serum samples are stored at À 20 1C until analyzed. 38 …”
In this paper, we provide a detailed protocol for a model of long bone mechanical marrow ablation in the rodent, including surgical procedure, anesthesia, and pre-and post-operative care. In addition, frequently used experimental end points are briefly discussed. This model was developed to study intramembranous bone regeneration following surgical disruption of the marrow contents of long bones. In this model, the timing of the appearance of bone formation and remodeling is well-characterized and therefore the model is well-suited to evaluate the in vivo effects of various agents which influence these processes. When biomaterials such as tissue engineering scaffolds or metal implants are placed in the medullary cavity after marrow ablation, end points relevant to tissue engineering and implant fixation can also be analyzed. By sharing a detailed protocol, we hope to improve inter-laboratory reproducibility.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.