Comparison of post-operative three-dimensional and two-dimensional evaluation of component position for total knee arthroplasty.

PURPOSE: The purpose of this study was to evaluate the post-operative three-dimensional (3D) femoral and tibial component positions in total knee arthroplasty (TKA) by the same co-ordinates' system as for pre-operative planning and to compare it with a two-dimensional (2D) evaluation. MATERIALS AND METHODS: Sixty-five primary TKAs due to osteoarthritis were included. A computed tomography (CT) scan of the femur and tibia was obtained and pre-operative 3D planning was performed. Then, 3D and 2D post-operative evaluations of the component positions were performed. KneeCAS (LEXI, Inc., Tokyo, Japan), a lower-extremity alignment assessment system, was used for the 3D post-operative evaluation. Standard short-knee radiographs were used for the 2D post-operative evaluation. Differences between the pre-operative planning and post-operative coronal and sagittal alignment of components were investigated and compared with the results of the 3D and 2D evaluations. RESULTS: According to the 3D evaluation, the difference between the pre-operative planning and actual post-operative sagittal alignment of the femoral component and the coronal and sagittal alignments of the tibial component were 2.6° ± 1.8°, 2.2° ± 1.8° and 3.2° ± 2.4°, respectively. Using the 2D evaluation, they were 1.9° ± 1.5°, 1.3° ± 1.2° and 1.8° ± 1.4°, making the difference in 3D evaluation significantly higher (p = 0.013, = 0.003 and < 0.001). For the sagittal alignment of the femoral component and the coronal and sagittal alignment of the tibial component, the outlier (> ± 3°) ratio for the 3D evaluation was also significantly higher than that of the 2D evaluation (p < 0.001, = 0.009 and < 0.001). CONCLUSIONS: The difference between the pre-operative planning and post-operative component alignment in the 3D evaluation is significantly higher than that of the 2D, even if the same cases have been evaluated. Two-dimensional evaluation may mask or underestimate the post-operative implant malposition. Three-dimensional evaluation using the same co-ordinates' system as for pre-operative planning is necessary to accurately evaluate the post-operative component position.

Correlation between posterior tibial slope and sagittal alignment under weight-bearing conditions in osteoarthritic knees.

INTRODUCTION: Posterior tibial slope (PTS) and sagittal alignment are important factors in the etiology of knee osteoarthritis and knee surgery. Clinically, sagittal alignment, which indicates flexion contracture of the knee, contributes to knee function in weight-bearing (WB) conditions. PTS and sagittal alignment under WB conditions in varus osteoarthritic knees are presumed to affect each other, but their association remains unclear. In this study, we aimed to clarify the association. MATERIAL AND METHODS: In total, 140 osteoarthritic varus knees were investigated. Under WB conditions, a three-dimensional (3D) alignment assessment system was applied via biplanar long-leg X-rays, using 3D-to-2D image registration technique. The evaluation parameters were as follows: 1) 3D mechanical flexion angle (3DMFA) in regards to sagittal alignment, 2) passing point in the WB line (PP), and 3) medial and lateral PTS. RESULTS: The medial and lateral PTS showed a positive correlation with 3DMFA and PP, respectively (medial PTS-3DMFA, p = 0.001; medial PTS-PP, p < 0.0001; lateral PTS-3DMFA, p < 0.0001; lateral PTS-PP, p = 0.002). The flexion contracture group with 3DMFA >5° demonstrated greater PTS than non-flexion contracture group (medial PTS, p = 0.006; lateral PTS, p = 0.006). CONCLUSIONS: Both medial and lateral PTS were correlated with sagittal alignment under WB conditions and were larger in the flexion contracture group. This finding can explain the function to take the load articular surface parallel to the ground for holding the balance in WB conditions in the sagittal plane for osteoarthritic knees. Moreover, surgeons may be required to decrease the PTS during knee arthroplasty to restore full extension in knees of patients with fixed flexion contracture.

Association between anteroposterior laxity in mid-range flexion and subjective healing of instability after total knee arthroplasty.

PURPOSE: Flexion instability following total knee arthroplasty (TKA) is a common indication of early revision. The association between the objective anteroposterior (AP) laxity direction in mid-range flexion and the subjective healing of instability remains unclear; thus, this study aimed to clarify this association. METHODS: In this study, 110 knees (74 females, 92 knees; 16 males, 18 knees) with medial pivot implants were examined with a median age of 79 (range 60-92) years for a median follow-up duration of 22 (range 6-125) months. AP laxity was measured using a KT-1000 arthrometer. Self-reported knee instability score was used for the subjective healing of instability. RESULTS: Eighty-seven knees did not feel unstable (Group 0), whereas 23 knees felt unstable (Group 1). There was a significant difference in AP displacement [Group 0: median 6 mm; range 2-15 mm and Group 1: median 8 mm; range 4-14; p < 0.0001]. The threshold value of 7 mm was determined using the area under receiver operating characteristic curve of 0.79 [95% confidence interval (CI) 0.69-0.88, p < 0.0001]. In multivariate analysis, AP displacement of ≥7 mm was an independent risk factor for feelings of instability (odds ratio 7.695; 95% CI 2.306-25.674; p = 0.001). CONCLUSIONS: AP laxity of ≥7 mm represents a known cause of feelings of instability. By controlling AP laxity in TKAs, without stiffness in the knee, it is possible to prevent feelings of instability. The clinical relevance is that AP laxity of <7 mm is one of the target areas in TKA. LEVEL OF EVIDENCE: IV.

Sex differences in femoral deformity determined using three-dimensional assessment for osteoarthritic knees.

PURPOSE: To characterize femoral deformities and determine sex differences in varus knee osteoarthritis (OA), femoral morphology and limb alignment were evaluated by using three-dimensional (3D) assessment, comparing healthy, elderly volunteers with osteoarthritic knees. METHODS: A total of 178 lower limbs of 169 subjects with knee osteoarthritis (136 women, 33 men; mean age 74.9 ± 5.2 years) and 80 lower limbs of 45 healthy, elderly subjects (24 women, 21 men; mean age 65 ± 4.9 years) were examined. A 3D extremity alignment assessment system was used to examine the subjects under weight-bearing conditions on biplanar long-leg radiographs using a 3D-to-2D image registration technique. The evaluation parameters were (1) femoral bowing in the coronal plane, (2) femoral bowing in the sagittal plane, (3) femoral neck anteversion, (4) hip-knee-ankle angle, and (5) femoral torsion. RESULTS: Higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis were observed in women with OA compared with healthy subjects. No difference in the higher varus malalignment, no alteration in the femoral anterior bowing, and no difference in the lower femoral neck anteversion were found between men and women when comparing healthy and OA subjects. CONCLUSIONS: The higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis in women are possibly a structural adaptation to mechanical use. The clinical significance is that the femoral deformities and the sex differences in knee OA have the potential to improve the understanding of the aetiology of primary varus knee OA. LEVEL OF EVIDENCE: IV.

Unicompartmental knee arthroplasty cannot restore the functional flexion axis of a living knee to normal.

PURPOSE: The purpose of this study was to investigate the hypothesis that a medial unicompartmental knee arthroplasty might restore the functional flexion axis of a knee to normal. The flexion axis can be indirectly identified by tracking the vertical translation of anatomic landmarks that basically move around the flexion axis during a knee motion. If a unicompartmental knee could help restore the normal flexion axis, the anatomic landmarks after the arthroplasty would show the vertical translation similar to those of normal knees during a knee flexion. METHODS: While performing a squatting motion, the kinematics of 17 knees were determined before and after a medial unicompartmental arthroplasty to calculate the vertical translation of a clinical epicondylar axis, using a three- to two-dimensional registration technique through a single-plane fluoroscopic system incorporating a biplanar static radiography. The results were compared with a normal data, and a statistical analysis including a two-way repeated-measured analysis of variance was performed. RESULTS: For the medial end, from 10° to 100° knee flexion, normal, osteoarthritic, and unicompartmental knees had the average superior vertical translation of 7.3 ± 4.2, 4.3 ± 7.2, and 2.4 ± 3.1 mm, respectively, with statistical significance between normal and unicompartmental knees (p < 0.001). The vertical translation did not return to normal post-implantation. CONCLUSIONS: A unicompartmental knee could not reproduce the normal flexion axis. As for clinical relevance, the changes of the implant design and surgical procedure may be necessary to obtain the normal flexion axis reproducing a normal motion. LEVEL OF EVIDENCE: IV.

Usefulness of urinary CTX-II and NTX-I in evaluating radiological knee osteoarthritis : the Matsudai knee osteoarthritis survey.

BACKGROUND: To assess the usefulness of the urinary crosslinked C-telopeptide of type II collagen (uCTX-II) or crosslinked N-telopeptide of type I collagen (uNTX-I) for evaluating radiological knee osteoarthritis (OA), a cross-sectional study was conducted in the cohorts of the Matsudai knee osteoarthritis survey performed in Niigata, Japan. METHODS: Urine specimens and standing knee AP X-rays were obtained from 1040 subjects who provided informed consent. The relationship between these markers and gender, age (patients aged 40-59 or 60-79 years), use of bisphosphonates, and OA grades (K-L classification) were analyzed. The diagnostic ability of uCTX-II to detect radiological knee OA was confirmed in the over 60-year-old subjects using a ROC curve. RESULTS: The over 60-year-old men with OA grade 3,4 group had significantly higher uCTX-II levels than the other OA grade groups. In the over 60-year-old women, the uCTX-II levels significantly increased according to the progression of the knee OA grade. No significant difference was observed between the uNTX-I levels in the different OA grade groups. From the standpoint of biomarkers, the higher quartiles of the uCTX-II and uNTX-I levels gradually included higher numbers of grade ≥2 OA subjects in the over 60 year-old women. The area under the curve (AUC) in ROC analysis of uCTX-II exhibited a significant association with the diagnosis of knee OA in women (AUC 0.63), although the accuracy was evaluated to be low in the single measurement of our health checkup-based analysis. CONCLUSIONS: This population-based study indicates that the uCTX-II level is strongly correlated with the knee OA grade in women over age 60. A further analysis is needed to clarify its predictive accuracy.

Kinematics of the knee after unicompartmental arthroplasty is not the same as normal and is similar to the kinematics of the knee with osteoarthritis.

PURPOSE: It is common to assert that restoration of normal knee kinematics is essential for the best functional result after knee arthroplasty. Previous studies using the progression of the geometric centre axis have suggested that kinematics after unicompartmental arthroplasty is markedly different from the normal. For this study, the transepicondylar axis was used because this axis is closer to the flexion axis and should be a better reference for motion. The following hypothesis was tested: the transepicondylar axis would again show that the postoperative kinematics does not restore normal motion and is closer to that before replacement. METHODS: Seventeen osteoarthritic knees were tested before and after unicompartmental arthroplasty using a three-dimensional to two-dimensional registration technique tracking the transepicondylar axis to calculate translation and rotation of this axis. Results were compared for the seventeen knees before and after arthroplasty and were compared to the normal knee as measured in our previous study. RESULTS: Similar motion patterns in the pre- and postoperative knees were shown but both the pre- and postoperative motion were markedly different from the normal knee. CONCLUSIONS: This result supported our hypothesis. The clinical relevance is that medial unicompartmental arthroplasty cannot restore the motion of the knee to normal in the living knee. Therefore, it would be expected that the patient for unicompartmental knee might not feel normal. It may not be possible depending on ligaments alone to restore the knee to normal, and the changes in the articular shapes and the surgical procedure may also be necessary.

In vivo pre- and postoperative three-dimensional knee kinematics in unicompartmental knee arthroplasty.

BACKGROUND: Pre- and postoperative knee kinematics in unicompartmental knee arthroplasty (UKA) can be theoretically related to clinical outcome and longevity after UKA with regard to ligament function and the degree of arthritic changes. However, the preoperative knee kinematics of patients indicated for UKA remain to be elucidated, and it is also unclear whether the preoperative kinematics can be maintained by the UKA procedure. The objective of this study was to examine the in vivo pre- and postoperative three-dimensional knee kinematics in UKA while referencing the normal knee kinematics reported in our previous study. METHODS: We analyzed the knee kinematics in 17 knees (14 patients) undergoing UKA via a three-dimensional to two-dimensional registration technique employing femoral condylar translation and femoral axial rotation. The pre- and postoperative knee kinematics during squat motion were evaluated in the same subjects, employing consistent evaluation parameters. RESULTS: On average, both pre- and postoperative knee kinematics in the range 10-100° of knee flexion demonstrated near-consistent femoral external rotation and anterior translation of the medial condyle and posterior translation of the lateral condyle. However, the mean femoral external rotation angle and the posterior translation of the lateral condyle postoperatively were significantly smaller than the values observed preoperatively. DISCUSSION: Although the patterns of preoperative knee motion were similar to those seen in normal knees, the magnitude of this motion varied widely between patients, so it was not necessarily representative of normal knees. These variations may be due to the varying degrees of arthritic changes caused by osteoarthritis. Although the patterns of knee kinematics were largely maintained by the UKA procedure, the causes of the significant reductions in the magnitude of motion upon performing the UKA procedure should be investigated in subsequent studies with a larger number of patients.

Three-dimensional in vivo motion analysis of normal knees employing transepicondylar axis as an evaluation parameter.

PURPOSE: The transepicondylar axis (TEA) has been used as a flexion axis of the knee and a reference of the rotational alignment of the femoral component. However, no study has showed dynamic normal knee kinematics employing TEA as the evaluation parameter throughout the full range of motion in vivo. The purpose of this study was to analyze dynamic kinematics of the normal knee through the full range of motion via the 3-dimensional to 2-dimensional registration technique employing TEA as the evaluation parameter. METHODS: Dynamic motion of the right knee was analyzed in 20 healthy volunteers (10 female, 10 male; mean age 37.2 years). Knee motion was observed as subjects squatted from standing with knee fully extended to maximum flexion. The following parameters were determined: (1) Anteroposterior translations of the medial and lateral ends of the TEA; and (2) changes in the angle of the TEA on the tibial axial plane (rotation angle). RESULTS: The medial end of the TEA demonstrated anterior translation (3.6 ± 3.0 mm) from full extension to 30° flexion and demonstrated posterior translation (18.1 ± 3.7 mm) after 30°, while the lateral end of the TEA demonstrated consistent posterior translation (31.1 ± 7.3 mm) throughout knee flexion. All subjects exhibited femoral external rotation (16.9 ± 6.2°) relative to the tibia throughout knee flexion. CONCLUSION: Compared to previously used parameters, the TEA showed bicondylar posterior translation from early flexion phase. These results provide control data for dynamic kinematic analyses of pathologic knees in the future and will be useful in the design of total knee prostheses.

Chondromodulin-1 directly suppresses growth of human cancer cells.

BACKGROUND: Chondromodulin-1 (ChM1), an endogenous anti-angiogenic factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. However, it is unclear whether the anti-tumor effect is due to not only the anti-vascularization effect of ChM1, but also its direct action against oncocytes. In the present study, we sought to determine whether ChM1 has a direct action on tumor cells. METHODS: BrdU incorporation assay was performed on human umbilical vein endothelial cells (HUVECs), normal human dermal fibroblasts (NHDFs), HepG2 cells and HeLa cells in the presence or absence of recombinant human ChM1 (rhChM1). An adenovirus that expresses ChM1, Ad-ChM1, was established and applied to the tumor xenografted in vivo, and to in vitro tumor cells cultured on plates or in soft agar. Cell cycle-related proteins and the phosphorylation of Erk, Akt, and GSK3beta, the downstream molecules of the extracellular matrix-integrin signaling pathways, in HepG2 cells treated with or without Ad-ChM1 were detected by western blot analysis. Luciferase reporter assays of STAT, GAS, and ISRE, which participate in another cytokine signaling pathway, ware performed in HepG2, HeLa, and HUVEC cells. RESULTS: ChM1 suppressed BrdU incorporation in HUVECs and in HepG2 cells dose-dependently, but did not suppress BrdU incorporation in NHDFs and HeLa cells cultured on plates. In soft agar, however, ChM1 suppressed the growth of HeLa cells, as well as HepG2 cells. Western blot analyses demonstrated that ChM1 decreased the levels of cyclin D1, cyclin D3, and cdk6 and increased those of p21cip1 without affecting the phosphorylation levels of Erk, Akt, and GSK3beta in HepG2 cells. The luciferase reporter assay demonstrated that ChM1 suppressed the transcriptional activities of STAT and GAS but not of ISRE. CONCLUSION: ChM1 directly suppressed the proliferation of tumor cells in an anchorage-independent manner. However, ChM1 did not alter the phosphorylation of downstream molecules, at which the signaling pathways through growth factor and cytokine receptors converge with the anchorage-dependent pathway. Our results show that ChM1 has a direct anti-tumor effect; moreover, this effect occurs by inhibiting the STAT signaling pathway.

Relationship between radiological knee osteoarthritis and biochemical markers of cartilage and bone degradation (urine CTX-II and NTX-I): the Matsudai Knee Osteoarthritis Survey.

Biochemical markers of cartilage and bone degradation are becoming increasingly important in the evaluation of knee osteoarthritis (OA). To clarify the correlation between radiological knee OA and urine CTX-II (C-terminal crosslinking telopeptide of collagen type II) or urine NTX-I (N-terminal crosslinking telopeptide of type I collagen), we conducted a cross-sectional study in the cohorts of the epidemiological knee survey at the Matsudai district in Niigata Prefecture, Japan. Urine specimens were collected from 296 subjects, and CTX-II and NTX-I were measured using ELISA. Standing knee AP X-rays were obtained and graded according to the Kellgren-Lawrence classification. The subjects were then divided by gender, age (40- to 59-year-old group and 60- to 79-year-old group), and the X-ray grade (Grade 0, 1, Grade 2, and Grade 3, 4). In non-OA (Grade 0, 1) subjects, the 60- to 79-year-old group had significantly higher CTX-II values than the younger group only in females. The subjects of both genders aged over 60 years of age with OA Grade 3, 4 had significantly higher CTX-II values than the Grade 0, 1 group or the Grade 2 group. For NTX-I, there were no significant differences between each OA grade although the Grade 3, 4 group females from 60 to 79 years of age had higher values than the Grade 2 group. In addition, in the 60- to 79-year-old subjects of both genders, a positive correlation was observed between the urine CTX-II and urine NTX-I. For the subjects ranging from 60 to 79 years of age in both genders, the urine CTX-II values indicate the progression of OA. In addition, the weak but positive correlation between urine CTX-II and urine NTX-I in the subjects ranging from 60 to 79 years of age in both genders suggests that bone resorption and cartilage degradation appear to develop in parallel.

Oligonucleotide decoy mimicking alphaA-crystallin-binding protein 1 binding site on mouse Col2a1 enhancer stimulates transcription from the adjacent Col2a1 promoter in chondrogenic ATDC5 cell.

A 48-bp sequence element in intron 1 of the alpha1(II) collagen gene (Col2a1) acts as an enhancer of Col2a1 transcription and contains binding sites for the transcription activator SOX9 and repressor alphaA-crystallin-binding protein 1 (CRYBP1). We hypothesized that abrogating CRYBP1 binding should increase transcription from a promoter associated with the Col2a1 enhancer. We tested this hypothesis by cotransfecting an oligonucleotide (ODN) decoy for CRYBP1 and a luciferase-based reporter vector under the transcriptional control of the Col2a1 promoter linked to the 100-bp enhancer in chondrogenic ATDC5 cells. As a control, we used decoy ODN corresponding to the SOX9 binding site. Transfection with CRYBP1 decoy increased luciferase activity by >2.5-fold in the absence or presence of insulin, whereas SOX9 decoy ODN decreased luciferase activity to about 50% under similar conditions. In addition, the repressive effect of interleukin-1 on Col2a1 transcription through decreasing SOX9 messenger ribonucleic acid (mRNA) expression and increasing CRYBP1 mRNA expression, was counteracted by CRYBP1 decoy ODN. These results provide a rationale for gene therapy in degenerative joint diseases by elevating Col2a1 expression in chondrocytes through oligomimetics of repressor binding sites.

Sclerosing epithelioid fibrosarcoma with der(10)t(10;17)(p11;q11).

Sclerosing epithelioid fibrosarcoma is a recently described, rare mesenchymal neoplasm. We report a case of sclerosing epithelioid fibrosarcoma that occurred in the lower leg of a 48-year-old man. The karyotype of the tumor exhibited der(1)t(1;10)(p31;p11), der(10)t(10;17)(p11;q11), and der(17) t(11;17)(?;q11). Rearrangement of 10p11 was also found in one previous reported case of this uncommon tumor.

Identification of estrogen-regulated genes during fracture healing, using DNA microarray.

Estrogen deficiency impairs fracture healing, while estrogen treatment of ovariectomized rats accelerates fracture healing. To identify genes regulated by estrogen during fracture healing, we evaluated gene expression in calluses from three groups of rats: sham-operated, ovariectomized, and ovariectomized and treated with estrogen. RNA from calluses harvested 10 days after fracture was subjected to DNA microarray-based analysis of 5147 genes. In total, 52 genes were identified whose mRNA expressions were found to be downregulated by ovariectomy but restored with estrogen. Differential mRNA expression of 4 genes (collagen type 2, extracellular superoxide dismutase, urokinase-type plasminogen activator [ u-PA], and ptk-3) was confirmed by reverse transcription polymerase chain reaction. Further, chondrocytes and chondroclasts were positive for u-PA in the junction between cartilage and bone, implying its importance in resorption and remodeling of callus. Identification of these genes is a prerequisite to understanding the mechanism by which estrogen influences the complex metabolic process of fracture repair.

Expression of the cartilage derived anti-angiogenic factor chondromodulin-I decreases in the early stage of experimental osteoarthritis.

OBJECTIVE: Chondromodulin-I (ChM-I), a cartilage derived anti-angiogenic factor, has been shown to regulate the vascular invasion during endochondral bone formation. We evaluated the expression and localization of ChM-I in articular cartilage during the progression of osteoarthritis (OA) in the rat, and correlated ChM-I expression with the increase in vascular invasion into OA articular cartilage. METHODS: Expression of ChM-I, type II collagen, basic fibroblast growth factor, vascular endothelial growth factor (VEGF), and matrix metalloproteinases MMP-9 and MMP-13 were examined in articular cartilage of intact growing and adult rats and in the surgically induced OA model using in situ hybridization, Western blot analysis, and immunohistochemistry. Co-immunostaining for ChM-I and CD-31 was performed to localize ChM-I and neovascularization in articular cartilage at advanced stage of OA. RESULTS: Abundant expression of ChM-I protein was detected in avascular regions of the developing and adult healthy articular cartilage. In early OA, ChM-I expression decreased in the superficial zone of articular cartilage, while levels of proteoglycan and type II collagen were comparable to control. In advanced OA, ChM-I expression was reduced in all zones of articular cartilage, and the number of VEGF-expressing cells was increased. Immunohistochemical studies showed that vascular invasion occurred in proximity to chondrocytes with high expression of pro-angiogenic markers, and decreased expression of ChM-I. CONCLUSION: High expression of ChM-I was detected in articular cartilage of growing and normal adult joints, implicating its role in the maintenance of avascularity of intact articular cartilage. Expression of ChM-I decreased, while expression of VEGF and other pro-angiogenic factors increased, in OA cartilage. These findings suggest the loss of ChM-I from articular cartilage might be responsible in part for promoting blood vessel invasion into the cartilage during progression of OA.

Effect of dexamethasone on growth inhibition and chondrogenic maturation of human chondrosarcoma.

The effect of dexamethasone, a synthetic glucocorticoid, on in vitro and in vivo growth and differentiation of the human chondrosarcoma cell line (OUMS-27) was studied. Cells were treated with various doses of dexamethasone, and increasing doses produced an inhibitory effect on OUMS-27 tumor cell proliferation and induced maturation. Cell counts for OUMS-27 on day 9 ranged from 59% of the control at 10(-8) M to 45% of the control at 10(-5) M dexamethasone. Northern blot analysis revealed that the type II collagen mRNA level in cells given dexamethasone was lower than that in the controls, and the type X collagen mRNA level was higher than that in the controls. Phase-contrast microscopy revealed that cells grown in control medium formed monolayers consisting of small, polygonal cells, whereas dexamethasone-treated cells became larger and more irregular in shape. In the in vivo study the growth rate of masses in nude mice induced by inoculating OUMS-27 cells was also reduced in a dose-dependent manner with dexamethasone administration. These results suggest that dexamethasone caused growth inhibition and induced chondrogenic maturation of human chondrosarcoma cells.