Correlation between the distal anterior femoral cortical axis and femoral rotational alignment: an anatomic study.

PURPOSE: To determine the correlation between the distal anterior femoral cortical axis (DAFCA) and the femoral rotational alignment/axis. METHODS: Magnetic resonance images (MRI) of 82 knees in 34 men and 23 women aged 16 to 47 (mean, 33.4) years were reviewed by a musculoskeletal radiologist. Their diagnoses included meniscal tear (n=4), chondromalacia (n=25), anterior cruciate ligament tears (n=11), and normal (n=42). In all patients the collateral ligaments were intact. The transepicondylar axis (TEA), posterior condylar axis (PCA), Whiteside line (WL), and joint line were drawn on the images, and the condylar twist angle (CTA), TEA-WL angle, DAFCA, epicondylar cortical angle (ECA), and condylar cortical angle (CCA) were measured. The correlations among ECA, CCA, and CTA (control) were assessed. RESULTS: The mean distances between the joint line and the TEA, PCA, and DAFCA were 30.8, 22.1, and 62.2 mm, respectively. The angles subtended by the intersection between the standard axes (TEA, PCA, and WL) and the DAFCA were determined. There was correlation between the CTA and ECA (r=0.34, p<0.05), between the ECA and the CCA (r=0.80, p<0.0001), and between the CTA and the CCA (r=- 0.19, p=0.08). CONCLUSION: There was correlation between the DAFCA and TEA and PCA; DAFCA can be used to determine the femoral rotational alignment when the standard landmarks are distorted by severe soft tissue and bone loss.

Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA.

OBJECTIVE: The study aimed determining whether assessment of cartilage oligomeric matrix protein (COMP) degradation products could serve as a serological disease course and therapeutic response predictor in arthritis. METHODS: We generated a panel of monoclonal antibodies against COMP fragments and developed a novel capture enzyme-linked immunosorbent assay (ELISA) for detecting COMP fragments in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This test was also used to monitor COMP fragments in surgically-induced OA, collagen-induced arthritis (CIA), and tumor necrosis factor (TNF) transgenic animal models. RESULTS: Compared with a commercial COMP ELISA kit that detected no significant difference in COMP levels between OA and control groups, a significant increase of the COMP fragments were noted in the serum of OA patients assayed by this newly established ELISA. In addition, serum COMP fragment levels were well correlated with severity in OA patients and the progression of surgically-induced OA in murine models. Furthermore, the serum levels of COMP fragments in RA patients, mice with CIA, and TNF transgenic mice were significantly higher when compared with their controls. Interestingly, treatment with TNFα inhibitors and methotrexate led to a significant decrease of serum COMP fragments in RA patients. Additionally, administration of Atsttrin [Tang, et al., Science 2011;332(6028):478] also resulted in a significant reduction in COMP fragments in arthritis mice models. CONCLUSION: A novel sandwich ELISA is capable of reproducibly measuring serum COMP fragments in both arthritic patients and rodent arthritis models. This test also provides a valuable means to utilize serum COMP fragments for monitoring the effects of interventions in arthritis.

Comparative analysis with collagen type II distinguishes cartilage oligomeric matrix protein as a primary TGFß-responsive gene.

OBJECTIVE: This study aims to investigate the regulation of expression of Cartilage oligomeric matrix protein (COMP), which is predominately expressed by chondrocytes and functions to organize the extracellular matrix. Mutations in COMP cause two skeletal dysplasias: pseudoachondroplasia and multiple epiphyseal dysplasia. The mechanism controlling COMP expression during chondrocyte differentiation is still poorly understood. DESIGN: Primary human bone marrow-derived stem cells were induced to differentiate into chondrocyte by pellet cultures. We then compared the temporal expression of COMP with the well-characterized cartilage-specific Type II collagen (Col2a1), and their response to transforming growth factor (TGF)ß and Sox trio (Sox5, 6, and 9) stimulation. RESULTS: COMP and Col2a1 expression are differentially regulated by three distinct mechanisms. First, upregulation of COMP mRNA precedes Col2a1 by several days during chondrogenesis. Second, COMP expression is independent of high cell density but requires TGF-ß1. Induction of COMP mRNA by TGF-ß1 is detected within 2h in the absence of protein synthesis and is blocked by specific inhibitors of the TGFß signaling pathway; and therefore, COMP is a primary TFGß-response gene. Lastly, while Col2a1 expression is intimately controlled by the Sox trio, overexpression of Sox trio fails to activate the COMP promoter. CONCLUSION: COMP and Col2a1 expression are regulated differently during chondrogenesis. COMP is a primary response gene of TGFß and its fast induction during chondrogenesis suggests that COMP is suitable for rapidly accessing the chondrogenic potential of stem cells.

Increased friction coefficient and superficial zone protein expression in patients with advanced osteoarthritis.

OBJECTIVE: To quantify the concentration of superficial zone protein (SZP) in the articular cartilage and synovial fluid of patients with advanced osteoarthritis (OA) and to further correlate the SZP content with the friction coefficient, OA severity, and levels of proinflammatory cytokines. METHODS: Samples of articular cartilage and synovial fluid were obtained from patients undergoing elective total knee replacement surgery. Additional normal samples were obtained from donated body program and tissue bank sources. Regional SZP expression in cartilage obtained from the femoral condyles was quantified by enzyme-linked immunosorbent assay (ELISA) and visualized by immunohistochemistry. Friction coefficient measurements of cartilage plugs slid in the boundary lubrication system were obtained. OA severity was graded using histochemical analyses. The concentrations of SZP and proinflammatory cytokines in synovial fluid were determined by ELISA. RESULTS: A pattern of SZP localization in knee cartilage was identified, with load-bearing regions exhibiting high SZP expression. SZP expression patterns were correlated with friction coefficient and OA severity; however, SZP expression was observed in all samples at the articular surface, regardless of OA severity. SZP expression and aspirate volume of synovial fluid were higher in OA patients than in normal controls. Expression of cytokines was elevated in the synovial fluid of some patients. CONCLUSION: Our findings indicate a mechanochemical coupling in which physical forces regulate OA severity and joint lubrication. The findings of this study also suggest that SZP may be ineffective in reducing joint friction in the boundary lubrication mode at an advanced stage of OA, where other mechanisms may dominate the observed tribological behavior.

Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin.

OBJECTIVE: As we previously reported, ADAMTS-7 and ADAMTS-12, two members of ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family, degrade cartilage oligomeric matrix protein (COMP) in vitro and are significantly induced in the cartilage and synovium of arthritic patients [Liu CJ, Kong W, Ilalov K, Yu S, Xu K, Prazak L, et al. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB J 2006;20(7):988-90; Liu CJ, Kong W, Xu K, Luan Y, Ilalov K, Sehgal B, et al. ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein. J Biol Chem 2006;281(23):15800-8]. The purpose of this study was to determine (1) whether cleavage activity of ADAMTS-7 and ADAMTS-12 of COMP are associated with COMP degradation in osteoarthritis (OA); (2) whether alpha-2-macroglobulin (a(2)M) is a novel substrate for ADAMTS-7 and ADAMTS-12; and (3) whether a(2)M inhibits ADAMTS-7 or ADAMTS-12 cleavage of COMP. METHODS: An in vitro digestion assay was used to examine the degradation of COMP by ADAMTS-7 and ADAMTS-12 in the cartilage of OA patients; in cartilage explants incubated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1-beta (IL-1beta) with or without blocking antibodies; and in human chondrocytes treated with specific small interfering RNA (siRNA) to knockdown ADAMTS-7 or/and ADAMTS-12. Digestion of a(2)M by ADAMTS-7 and ADAMTS-12 in vitro and the inhibition of ADAMTS-7 or ADAMTS-12-mediated digestion of COMP by a(2)M were also analyzed. RESULTS: The molecular mass of the COMP fragments produced by either ADAMTS-7 or ADAMTS-12 were similar to those observed in OA patients. Specific blocking antibodies against ADAMTS-7 and ADAMTS-12 dramatically inhibited TNF-alpha- or IL-1beta-induced COMP degradation in the cultured cartilage explants. The suppression of ADAMTS-7 or ADAMTS-12 expression by siRNA silencing in the human chondrocytes also prevented TNF-alpha- or IL-1beta-induced COMP degradation. Both ADAMTS-7 and ADAMTS-12 were able to cleave a(2)M, giving rise to 180- and 105-kDa cleavage products, respectively. Furthermore, a(2)M inhibited both ADAMTS-7- and ADAMTS-12-mediated COMP degradation in a concentration (or dose)-dependent manner. CONCLUSION: Our observations demonstrate the importance of COMP degradation by ADAMTS-7 and ADAMTS-12 in vivo. Furthermore, a(2)M is a novel substrate for ADAMTS-7 and ADAMTS-12. More significantly, a(2)M represents the first endogenous inhibitor of ADAMTS-7 and ADAMTS-12.

Surface damage to an Oxinium femoral head prosthesis after dislocation.

During open reduction of an irreducible anterior dislocation of a total hip replacement with an Oxinium femoral head, it was observed that the head had been significantly damaged. Gross and scanning electron microscopic examination revealed cracking, gouging, and delamination of the surface. Because of the risk which this poses for damaging the polyethylene acetabular liner, it is strongly recommended that patients with this type of prosthetic head be carefully monitored after a dislocation.

Cavitary acetabular defects treated with morselized cancellous bone graft and cementless cups.

The use of impacted morselized cancellous bone grafts in conjunction with cementless hemispherical acetabular cups for treatment of AAOS type II acetabular cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24 revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years, respectively. All primary hips received autografts, while all revision hips received allografts. Modified Harris Hip Scores for primary and revision hip replacements increased from a pre-operative mean of 37 and 47 to a postoperative mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous allografts were radiographically incorporated without evidence of resorption. There were no instances of infection, component migration, or cases requiring subsequent acetabular revision. We conclude that impacted morselized cancellous bone-graft augmentation of cementless cups is a viable surgical option for AAOS type II cavitary acetabular defects.

COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer.

BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. METHODS: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Midterm clinical and radiographic results with the genesis I total knee prosthesis.

The midterm results of primary posterior cruciate ligament-retaining, minimally conforming, cemented modular total knee arthroplasties using the Genesis I prosthesis in 110 knees in 72 patients were reviewed. Patients were evaluated at a mean follow-up of 7.3 years by Knee Society pain and functional scores, radiographic and survivorship analysis, and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) health status questionnaire. Range of motion increased from an average of 96.3 degrees to 112.5 degrees. Knee Society pain and functional scores increased from preoperative averages of 55 and 44 to 92 and 88, respectively. There were 91 excellent, 16 good, 1 fair, and 2 poor results. WOMAC scores were increased significantly in each subcategory examined (pain, stiffness, and physical function). Kaplan-Meier survivorship was 97% at 10 years. An increase in loosening as a result of eccentric stress concentration secondary to the nonconforming design of this prosthesis, theoretically a matter of some clinical concern, was not shown in this investigation.

Efficacy of combined technetium-99m sulfur colloid/indium-111 leukocyte scans to detect infected total hip and knee arthroplasties.

The reliability of combined indium-111 leukocyte/technetium-99m sulfur colloid scans, with and without the addition of blood pooling and blood flow studies, in the diagnosis of infected total joint arthroplasty was investigated. Both scans were performed on 58 patients before reoperation of total hip or knee arthroplasty in the period 1996-1999. Results for imaging alone included 100% specificity, 46% sensitivity, 100% positive predictive value, 84% negative predictive value, and 88% accuracy. Inclusion of blood pooling and flow phase data improved results to 66% sensitivity, 89% negative predictive value, and 90% accuracy, with reductions in specificity (98%) and positive predictive value (91%). Routine use of these radionuclide scans is not supported by these data.

Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging-detected bone bruises after acute anterior cruciate ligament tears.

Histologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI-detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme-linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10-fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions.

Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts.

Cartilage oligomeric matrix protein has been implicated as an important component of endochondral ossification because of its direct effects on chondrocytes. The importance of this protein for skeletal development and growth has been recently illustrated by the identification of mutations in cartilage oligomeric protein genes in two types of inherited chondrodysplasias and osteoarthritic phenotypes: multiple epiphyseal dysplasia and pseudoachondroplasia. In the present study, we report the presence of cartilage oligomeric protein in embryonic and adult osteoblasts. A foot from a 21-week-old human fetus, subchondral bone obtained from knee replacement surgery in an adult patient, and a limb from a 19-day-postcoital mouse embryo were analyzed with immunostaining and in situ hybridization. In the human fetal foot, cartilage oligomeric protein was localized to osteoblasts of the bone collar and at the newly formed bone at the growth plate and bone diaphyses. Immunostaining was performed on the adult subchondral bone and showed positive intracellular staining for cartilage oligomeric protein of the osteoblasts lining the trabecular bone. There was no staining of the osteocytes. Immunostaining of the mouse limb showed the most intense staining for cartilage oligomeric protein in the hypertrophic chondrocytes and in the surrounding osteoblast cells of the developing bone. Cartilage oligomeric protein mRNA and protein were detected in an osteoblast cell line (MG-63), and cartilage oligomeric protein mRNA was detected from human cancellous bone RNA. These results suggest that the altered structure of cartilage oligomeric protein by the mutations seen in pseudoachondroplasia and multiple epiphyseal dysplasia may have direct effects on osteoblasts, contributing to the pathogenesis of these genetic disorders.

Reconstruction of the failed femoral component and proximal femoral bone loss in revision hip surgery.

Advances in implant technology and surgical techniques have greatly improved the results of femoral stem revision in total hip arthroplasty. The 10-year results obtained with extensively coated noncemented revision stems parallel those obtained with cemented stems revised by using contemporary techniques. Proximal femoral bone loss is an important consideration when planning and performing revision arthroplasty. Proximal femoral bone defects can be managed with either metal or bone. Insignificant defects can be reconstructed by using primary hip arthroplasty techniques. Proximal femoral replacement prostheses are best restricted to sedentary elderly patients. Cortical strut grafts can be used reliably to reconstruct noncircumferential segmental defects. Calcar allografts are associated with unacceptably high rates of resorption. Proximal femoral allografts with either noncemented or cemented long-stem prostheses have the potential advantage of biologic soft-tissue attachment and restoration of bone stock. Impaction allografting with cement is indicated for cavitary defects and may also restore bone stock.

The genetic basis of the osteochondrodysplasias.

The osteochondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth and remodeling of cartilage and bone, affecting from 2 to 4.7 per 10,000 individuals. Most osteochondrodysplasias are heritable and many have elaborate patterns of genetic transmission. Affected individuals generally require management by multidisciplinary teams of specialists. In this review, we divide the osteochondrodysplasias into groups based on their genetic relationships, including mutations in various types of collagen, fibroblast growth factor, cartilage oligomeric matrix protein, parathyroid hormone receptor, the diastrophic dysplasia sulfate transporter, enzymes such as steroid sulfatases, transcription factor SOX9, and a cysteine proteinase, cathepsin K. We describe the major osteochondrodysplasias, define their causes and clinical manifestations, and provide the orthopaedic surgeon with an understanding of the underlying molecular defects as well as the anatomical aspects of these disorders.

The predictive value of indium-111 leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties.

To evaluate the usefulness of the indium-111 scan in detecting actually or potentially infected total hip, knee, and resection arthroplasties, 153 scans were performed on 143 patients who underwent reoperation for a loose or painful total joint arthroplasty or a resection arthroplasty between 1990 and 1996. Scans were interpreted as infected, not infected, or equivocal by an experienced nuclear medicine radiologist. Patients were considered to be infected if they met any 2 of the following criteria: i) positive intraoperative cultures, ii) final permanent histologic section indicating acute inflammation, and iii) intraoperative findings of gross purulence within the joint. Twenty-six patients (17%) met the infection criteria at the time of reoperation. Indium scans were found to have a 77% sensitivity, 86% specificity, 54% and 95% positive and negative predictive values, and 84% accuracy for the prediction of infection. Of 6 equivocal scans, none were infected. The results of this study suggest limited indications for the use of the indium-111 scan in the evaluation of painful hip, knee, or resection arthroplasties. A negative indium scan may be helpful in suggesting the absence of infection in cases in which the diagnosis is not otherwise evident.

Hip arthroplasty with a collared straight cobalt-chrome femoral stem using second-generation cementing technique: a 10-year-average follow-up study.

Clinical and radiographic results of 116 patients who had undergone 132 hip arthroplasties at our institution from 1983 to 1988 with a collared cemented straight cobalt-chrome femoral stem using second-generation cementing technique were reviewed. Twenty hips in 20 patients who were part of the original cohort were lost to follow-up. Mean age at the time of surgery was 68.2 years. Mean radiographic follow-up was 9.6 years with a minimum follow-up of 5 years. Ten-year survivorship of the component was 96.5% with revision considered as an endpoint and 94.2% with either revision or radiographic loosening considered the endpoint. Three implants (2.3%) were revised for aseptic loosening at a mean of 8.1 years after implantation. One implant (0.8%) was revised for septic loosening at 10.5 years after surgery. Of the implants not revised, 1 showed evidence of circumferential bone-cement radiolucencies, and 1 had radiolucencies at the implant-cement interface. Five of the surviving femoral components (5.0%) showed focal areas of cystic osteolysis, and proximal femoral bone resorption under the collar was seen in 32 patients (31.7%). There were no cases of cement fracture or stem subsidence. The biomechanical and material properties of this stem combined with second-generation cementing technique look promising for long-term survivorship.

Viscosupplementation for osteoarthritis.

Viscosupplementation therapy can restore the elastic and viscous properties of synovial fluid and thus recreate the intra-articular joint homeostasis that is disrupted in the degenerative joint. Hyaluronan (hyaluronic acid) products have been developed and used for viscosupplementation therapy in osteoarthritis. Viscosupplementation treatments using these products are well tolerated. Because viscosupplementation therapy is based on the concept of replenishing a normal physiological component of synovial fluid and cartilaginous tissue, exogenous administration of hyaluronic acid has the potential to have few side effects or local or systemic reactions. Viscosupplementation represents an alternative treatment for patients with osteoarthritis in which oral medications and/or surgery are not options or are ineffective.

Anticoagulant treatment of thromboembolism with intravenous heparin therapy in the early postoperative period following total joint arthroplasty.

BACKGROUND: Treatment of thromboembolism with intravenous heparin therapy in the early postoperative period after total joint arthroplasty has been associated with a high rate of complications. The purpose of the present study was to compare the rate of bleeding complications in a group of patients who required intravenous heparin therapy for the treatment of thromboembolism after total hip or knee arthroplasty with the rate in a control group of patients who received only prophylactic anticoagulation. METHODS: The postoperative courses of forty-four consecutive patients who were managed with intravenous administration of heparin and oral administration of warfarin for the treatment of a thromboembolic event following unilateral total hip or knee arthroplasty were compared with those of a control group of 376 consecutive patients who had these same procedures but did not have a thromboembolic complication. The patients in the control group were managed with prophylactic anticoagulation with use of enoxaparin. Sixty-eight percent (thirty) of the forty-four patients in the heparin group received the initial dose of heparin on or before the fourth postoperative day, and 82 percent (thirty-six) received an initial bolus of 5000 units of heparin at the initiation of therapy. RESULTS: The rate of bleeding complications was 9 percent (four of forty-four) in the heparin group, compared with 6 percent (twenty-three of 376) in the control group (p = 0.44). The mean transfusion requirement in the heparin group (1.8 units of packed red blood cells) was significantly greater than that in the control group (0.8 unit) (p < 0.0001). Three of the four patients who had a bleeding complication while receiving heparin and warfarin had coagulation parameters that were substantially higher than recommended levels. The mean duration of hospitalization in the heparin group (fifteen days) was significantly longer than that in the control group (seven days) (p < 0.0001). CONCLUSIONS: The results of the present study suggest that the use of intravenous heparin therapy for the treatment of thromboembolism in the early postoperative period after total joint arthroplasty is associated with a rate of bleeding complications that is similar to that associated with the use of prophylactic anticoagulation with use of enoxaparin alone. One should expect an increased transfusion requirement and a longer duration of hospitalization for patients who require intravenous heparin therapy for the treatment of a thromboembolic event.

Wear rates of ceramic-on-ceramic bearing surfaces in total hip implants: a 12-year follow-up study.

A retrospective clinical and radiographic analysis was performed on 58 patients (60 hips; mean age at time of surgery, 45.2 years) at a minimum of 10-year follow-up (mean, 12.7 years) after total hip replacement using a ceramic-on-ceramic hearing total hip implant (Autophor, Smith and Nephew, Memphis, TN). Mean wear rate at final follow-up was 0.21 mim, averaging 0.016 mm/y. There were no cases of periprosthetic osteolysis in the acetabuulum or femur. For the unrevised components, there were 3 (5%) cases of protrusio acetabuli and 4 (7%) cases of acetabular component loosening. On the femoral side, 78.3% had distal pedestal formation, and 83% had greater than 2 mm implant-bone radiolucencies in more than 5 Gruen zones as a result of gross motion of the stem. Despite radiographic evidence of implant loosening, this hard bearing articulation functioned well in vivo for more than 12 years with remarkably low wear--approximately one tenth the rate reported for metal-on-polyethylene total hip bearings.