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.

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.

The Quadriceps Vector is Most Parallel to the Spherical Axis With Minimal Difference for Gender or Ethnicity.

BACKGROUND: The extensor mechanism may be the key to kinematic alignment of total knee arthroplasty. The purpose of this study was to determine any differences in the direction of the quadriceps vector based on gender or ethnicity and to determine which anatomically derived alignment axis is closest to the quadriceps vector. METHODS: Computed tomography scans and patient records for 14 Caucasians (9 men and 5 women) and 40 Japanese (19 men and 21 women) were evaluated. Three axes of alignment-anatomic, mechanical, and spherical-were identified, measured, and compared to the quadriceps vector in each case. Principal component analysis was used to determine the quadriceps vector by using 3-dimensional models of muscles on computed tomography scans. RESULTS: No statistically significant differences in the orientation of the quadriceps vector were found based on gender or ethnicity, and the quadriceps vector was most closely aligned with the spherical axis. CONCLUSION: Because the quadriceps is the primary knee extensor, the spherical axis therefore may be a ubiquitous guide to alignment of the arthroplasty knee based on motion.

Three-dimensional in vivo dynamic motion analysis of anterior cruciate ligament-deficient knees during squatting using geometric center axis of the femur.

BACKGROUND: Anterior cruciate ligament (ACL) injury often leads to symptoms of instability, which may cause meniscus injury, osteochondral lesions, and degenerative changes. For thorough evaluation of the effects of abnormal motion of ACL-deficient (ACLD) knees on the meniscus and articular cartilage, it is necessary to assess tibiofemoral motion in the medial and lateral compartments separately. Our aim was to determine if in vivo three-dimensional (3D) dynamic motion of ACLD knees differs from that of contralateral uninjured knees by assessing knee motion in the medial and lateral compartments respectively. METHODS: A total of 22 patients with an isolated ACL-injured knee were examined. 3D to two-dimensional registration was used to determine 3D knee motion during squatting from full knee extension to full flexion for both ACLD and contralateral uninjured knees. The knee motion was evaluated by the movement of the geometric center axis of the femur projected onto the tibial axial plane. RESULTS: In ACLD knees the lateral femoral condyle was located significantly more posteriorly during nearly full extension than in contralateral uninjured knees. The range of anteroposterior translation of the medial femoral condyle was significantly greater than those of contralateral uninjured knees. Almost all of the contralateral uninjured knees demonstrated medial pivot motion, while the ACLD knees showed higher variance. CONCLUSIONS: The ACLD knees exhibited a motion pattern different from those of contralateral uninjured knees with higher variance. During nearly full extension of the ACLD knees, the lateral femoral condyle translated posteriorly and the screw-home movement seemed to be impaired. The ACL might have an important role in maintaining normal knee function, especially during the early flexion phase. The larger range of anteroposterior translation of the medial femoral condyle in ACLD knees may be associated with a risk of secondary meniscal injury and degenerative change in the articular cartilage. LEVEL OF EVIDENCE: Level 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.

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.

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.

The clinical epicondylar axis is not the functional flexion axis of the human knee.

BACKGROUND: The functional flexion axis (FFA) is the principal axis around which the knee moves and thus, by definition, does not move in vertical displacement relative to the tibia. The transepicondylar axis (TEA) has been reported to coincide with the FFA. If that is not true, the TEA should show vertical displacement during motion, and this hypothesis was investigated. METHODS: Three-dimensional knee kinematics of 20 healthy volunteers were determined during a squatting motion via a 3-dimensional to 2-dimensional image registration technique by calculating the vertical displacement of the clinical epicondylar axis (CEA) through the full range of motion. RESULTS: From 0° to 90° knee flexion, the average vertical displacement of the lateral end of the CEA was <3 mm, whereas that of the medial end was large (7.6 mm). DISCUSSION: The large vertical displacement of the medial end of the CEA suggests that the CEA is not the FFA. This finding implies that the CEA may not be an appropriate axis for a TKA prosthesis having a "single radius" design. EVIDENCE LEVEL: Level IV.

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.

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 using single-plane fluoroscopy.

BACKGROUND: Analysis of the movement of anatomically defined reference axes at the femoral condyles relative to the tibia is appropriate for evaluating knee kinematics. However, such parameters have been previously employed only in studies utilizing stop-motion techniques. The purpose of this study was to evaluate in vivo dynamic kinematics for full range of motion in normal knees using the three-dimensional to two-dimensional registration technique and to compare them with previously reported normal knee kinematics obtained via stop-motion techniques. 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 when subjects squatted from standing with the knee fully extended to maximum flexion. We determined the following parameters: (1) changes to angles of the geometric center axis (GCA) on the tibial axial plane (rotation angle); (2) anteroposterior translations of the medial and lateral ends of the GCA; and (3) motion patterns in each phase during knee flexion. RESULTS: All subjects exhibited femoral external rotation (26.1°) relative to the tibia throughout knee flexion. The medial femoral condyle demonstrated anterior translation (5.5 mm) from full extension to 100° flexion, and demonstrated posterior translation (3.9 mm) after 100°, while the lateral femoral condyle demonstrated consistent posterior translation (15.6 mm) throughout knee flexion. All subjects showed medial pivot motion from full extension to nearly 120° flexion. From 120° flexion, bicondylar rollback motion was observed. DISCUSSION: Although the behavior of the medial femoral condyle in our analysis differed somewhat from that seen in previous cadaver studies, the results obtained using dynamic analysis were generally equivalent to those obtained in previous studies employing stop-motion techniques. These results provide control data for future dynamic kinematic analyses of pathological knees.

The three-dimensional quadriceps vector is most parallel to the spherical axis in Japanese varus osteoarthritic knees.

BACKGROUND: The quadriceps femoris may be a reliable reference to proper alignment in total knee arthroplasty (TKA). We previously showed the quadriceps vector (QV) to be the most parallel to the spherical axis (SA-center hip to center medial condyle) for healthy knees. The purpose of this study was to determine whether the QV is the most parallel to the SA in knees with varus osteoarthritis (OA). METHODS: CT imaging for 35 varus OA and 40 healthy Japanese knees was used to construct 3D models of the femur, patella and each quadriceps component for each subject. The QV was calculated using principal component analysis for direction and was compared with the relationship of the QV to the measurement axes of the lower extremity, including the anatomical, mechanical and spherical axes. RESULTS: The direction of the QV for the OA knee group was different from that for the healthy knee group in 3D space (medio-lateral direction: women, p = 0.532, men, p = 0.540; antero-posterior direction: women, p = 0.141, men, p < 0.001). However, the angle of the QV in relation to measurement axes in the coronal plane was closest to the SA in both groups (around 1°), with no difference between the groups (women, p = 0.382, men, p = 0.943). CONCLUSION: In the coronal plane, the SA most closely approximates the QV for both healthy and OA knees. The more posterior QV position in the 3D space may affect the patellofemoral joint.

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.

[Bone and joint diseases in children. Etiology and pathogenesis of osteochondral lesions in children. Osteochondritis dissecans and osteochondrosis].

Osteochondral lesions in children mainly occur in the physeal and epiphyseal cartilage. Osteochondritis dissecans and osteochondrosis (apophysitis) are common and clinically important chronic disorders. These etiology and pathogenesis have also been well investigated in the Veterinary medicine in recent years. One of the most likely causes is proposed as a failure of blood supply to growth cartilage and following focal disturbance of endochondral ossification. Mechanical stress, trauma, rapid growth, anatomic conformation, and dietary imbalances would modify this initial step and break down the normal structure. In human, above-mentioned pathological changes can be detected using recent MRI technology, which contribute quite much in the early diagnosis of lesions in clinic. Another problem in children is acute traumatic growth plate injury, which increases the risk of the early closure of growth plate and following deformity of bone and joint. Early diagnosis and precise treatment are extremely important for children to prevent residual deformity and pain and growth disturbance. In future, less-invasive as well as effective treatments for the focally disturbed or accelerated ossification should be developed.

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.

[Bone fracture and the healing mechanisms. Histological aspect of fracture healing. Primary and secondary healing].

It is quite important to understand the histological aspect of fracture healing. It is helpful in the clinical practice to recognize how fracture management induces biological reaction. Repair process is classified into primary and secondary fracture healing. Primary healing is direct bone repair without endochondral ossification, which includes cartilaginous callus formation. This pattern does not usually happen in the natural process of fracture healing. Bone remodeling initially occurs under the stable condition of fracture with rigid fixation and no gap formation. The key of this process is Haversian canal remodeling and reestablishment of blood vessels. Secondary healing is typically characterized by three overlapping stages: the initial inflammatory response, callus formation (soft and hard callus), initial bony union and bone remodeling. Most of fracture repair in the clinic follow this process, and callus formation is confirmed with X-ray. The key of this process is the appropriate stability of the fracture site to maintain biological healing response.

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.

Pregnancy associated plasma protein-A is necessary for expeditious fracture healing in mice.

Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that regulates IGF bioavailability in vitro through cleavage of inhibitory IGF-binding protein-4 (IGFBP-4), has been implicated in skeletal development and injury repair responses. However, direct in vivo data are lacking. In this study, we used PAPP-A knock-out (KO) mice to determine the role of PAPP-A in fracture repair. Stabilized mid-shaft fractures were produced in femurs of 3-month-old mice. At 14 days post-fracture, complete bony bridging of the fracture callus was seen radiographically in wild-type but not in PAPP-A KO mice. Histological examination 5 to 28 days post-fracture showed reductions in the amount of intramembranous bone formation, cartilage production, endochondral ossification and remodeling in PAPP-A KO compared with wild-type mice. However, fracture healing appeared similar in both groups at 42 days post-fracture when analyzed by histology. A similar degree of healing strength in wild-type and PAPP-A KO femurs was demonstrated by mechanical testing at 28 and 42 days post-fracture. Untreated cultures of day 5 fracture calluses from wild-type mice showed robust IGFBP-4 protease activity and IGF receptor phosphorylation, whereas fracture calluses from PAPP-A KO mice had no IGFBP-4 protease activity and reduced IGF receptor phosphorylation. These data demonstrate a marked delay in fracture healing in PAPP-A KO compared with wild-type mice, and suggest that PAPP-A is necessary in the early phases of the process for expeditious fracture repair. The ability of PAPP-A to enhance local IGF action may be an important mechanism for optimizing the fracture repair response.

[Up-date of cartilage repair technique].

There are two major conditions which require cartilage repair, one is partial cartilage defect due to trauma or osteochondritis dissecanse and the other is cartilage degeneration and loss induced by osteoarthritis. In this section, we introduce several surgical techniques which are available in clinical cases. In patient with relatively small traumatic cartilage defect, microfracture technique, autologous osteochondral graft transplantation, or autologous cultured chondrocytes transplantation are performed. In patients with osteoarthritis, which usually larger region is affected than traumatic cartilage defect, cell based technique and osteochondral transplantation are not sufficient to cover the region, therefore abrasion arthroplasty is performed accompanied with osteotomy to correct mechanical property in the joint.