Anterior Cruciate Ligament (ACL)-injured Knees with Meniscal Ramp Lesions Manifest Greater Anteroposterior and Rotatory Instability Compared with Isolated ACL-injured Knees.

PURPOSE: To investigate the effects of ramp lesion (RL) and its repair on knee instability in patients with anterior cruciate ligament (ACL) injury by quantitatively assessing anteroposterior and rotational knee instability before and after ACL reconstruction. METHODS: All primary double-bundle ACL reconstruction using hamstring autografts between 2016 and 2021 were evaluated retrospectively. Patients with RLs without other meniscal injuries were included in Group R, whereas those with isolated ACL injuries constituted Group C. RL was repaired using all-inside devices in all patients in Group R. Knee instability, including the amount of anterior tibial translation (ATT), and the acceleration and external rotational angular velocity of the knee joint (ERAV) during the pivot-shift test were assessed at the time of surgery. The pivot-shift test grade was recorded. RESULTS: A total of 73 patients were included in this study. Preoperatively, Group R (n=23) had significantly greater pivot-shift grades (P=.039), ATT (6.0 mm: Group R; 4.5 mm: Group C, P<.001), acceleration (6.8; 2.8, P=.037), and ERAV (3.9; 2.8, P=.001) than Group C (n=50). Intraoperatively, ATT (-1.0 mm; -1.0 mm, P<.001), acceleration (1.2; 1.1, P<.001), and ERAV (1.4; 1.2, P<.001) were significantly decreased compared with the preoperative values in both groups. No significant differences in these values were observed between Groups R and C. CONCLUSIONS: ACL-injured knees accompanied by RLs exhibited significantly greater anteroposterior and rotatory instability than knees with isolated ACL injuries; increased knee instability can be effectively addressed by performing RL repair in conjunction with ACL reconstruction. The quantitative assessments employed-specifically measuring ATT, acceleration and ERAV during the pivot-shift test-have allowed us to delineate these aspects of knee instability with greater precision. LEVEL OF EVIDENCE: Level Ⅲ, retrospective comparative study.

Factors Associated With Residual Pivot Shift After ACL Reconstruction: A Quantitative Evaluation of the Pivot-Shift Test Preoperatively and at Minimum 12-Month Follow-up.

Background: Postoperative residual rotatory laxity remains despite improvement in surgical techniques for anterior cruciate ligament (ACL) reconstruction (ACLR). Purpose: To evaluate factors associated with residual pivot shift after ACLR by quantitative measurement of the pivot shift before and after surgery. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 97 patients who underwent primary double-bundle ACLR between June 2016 and March 2021 and underwent surgery to remove staples, with at least 12 months of follow-up evaluation, were enrolled. Quantitative measurements were performed under general anesthesia immediately before ACLR (preoperatively), after temporary fixation of the ACL graft (intraoperatively), and immediately before staple removal (postoperatively). The laxity of pivot shift was assessed using inertial sensors to measure acceleration and external rotational angular velocity (ERAV). Descriptive data were assessed for associations with postoperative acceleration and ERAV in a univariate analysis. A multiple linear regression analysis was performed to identify factors associated with postoperative acceleration and ERAV. Results: Anterior tibial translation, acceleration, and ERAV increased from intra- to postoperatively (P < .05). Factors significantly associated with postoperative acceleration were age (ß = -0.238; P = .021), lateral posterior tibial slope (PTS) (ß = 0.194; P = .048), and preoperative acceleration (ß = 0.261; P = .008). Factors significantly affecting postoperative ERAV were age (ß = -0.222; P = .029), ramp lesions (ß = 0.212; P = .027), and preoperative ERAV (ß = 0.323; P = .001). Conclusion: Greater preoperative laxity in the pivot shift was the factor having the most significant association with residual pivot shift after ACLR using quantitative measurements under general anesthesia. Younger age, higher lateral PTS, and concomitant ramp lesions were significant predictors of residual pivot shift. These findings can help pre- and intraoperative decision-making regarding whether an anterolateral structure augmentation should be added.

A Lateral Fracture Line Affects Femoral Trochanteric Fracture Instability and Swing Motion of the Intramedullary Nail: A Biomechanical Study.

Background: An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Methods: Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Results: Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). Conclusions: This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

Efficacy of all-inside devices in reducing gap and step-off in knee extension for ramp lesion repair: A cadaveric study.

PURPOSE: The aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all-inside device. METHODS: Eight Thiel-embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step-off (0: no step-off; 1: cross-sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all-inside repairs of the ramp lesions using all-inside devices were conducted. Dissection was performed to confirm the position of anchor fixation. RESULTS: As the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step-off grade decreased as the knee was extended, and the step-off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step-off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step-off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon. CONCLUSION: Suturing with an all-inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study. LEVEL OF EVIDENCE: Level IV.

Endosteal strut using a hydroxyapatite/poly-L-lactide mesh tube with a proximal humeral locking plate for the treatment of proximal humeral fractures.

PURPOSE: Proximal humeral fractures cause large intramedullary bone defects after humeral-head reduction. Hydroxyapatite/poly-L-lactide (HA/PLLA) materials are widely used for various fractures. However, the efficacy of endosteal strut using a HA/PLLA mesh tube (ES-HA/PLLA) with a locking plate for treating proximal humeral fractures was not reported. The purpose of this study is to examine the efficacy of ES-HA/PLLA with a proximal humeral locking plate in proximal humeral fractures. METHODS: Seventeen patients with proximal humeral fractures treated using ES-HA/PLLA with a locking plate from November 2017 to November 2021 were evaluated. The range of motion of the shoulder and postoperative complications were assessed at the final follow-up. Radiographs were evaluated to assess bone union and loss of reduction by measuring humeral-head height (HHH) and humeral neck-shaft angle (NSA). RESULTS: The average flexion and external rotation of the shoulder at the final follow-up were 137° (range, 90-180°) and 39° (range, - 10 to 60°), respectively. All fractures were united. The average HHH and NSA just after the surgery and final follow-up were 12.5 mm and 11.6 mm and 129.9° and 127.4°, respectively. Two patients presented screw perforation of the humeral head. One patient underwent implant removal due to infection. Avascular necrosis of the humeral head was observed in one patient with arthritis mutilans. CONCLUSIONS: The use of ES-HA/PLLA with a proximal humeral locking plate resulted in bone union in all patients and prevented postoperative loss of reduction. ES-HA/PLLA is one of the treatment options for proximal humeral fractures.

HSP70 inhibitor amplifies the bFGF­induced release of IL­6 in osteoblasts.

Heat shock protein 70 (HSP70) functions as an ATP­dependent molecular chaperone under stress and is involved in protein homeostasis, folding and degradation. HSP70 inhibitors amplify TGF­ß­stimulated VEGF synthesis in the mouse osteoblastic MC3T3­E1 cell line. Basic fibroblast growth factor (bFGF) stimulates IL­6 release via p38 MAPK in MC3T3­E1 osteoblast­like cells. In the present study, the effects of HSP70 on the bFGF­stimulated release of IL­6 was evaluated using MC3T3­E1 osteoblast­like cells. IL­6 release and mRNA expression levels were analyzed using ELISA and reverse transcription­quantitative PCR, respectively. Phosphorylation of p38 MAPK and HSP70 was assessed using western blotting. HSP70 inhibitor VER­155008 significantly increased the bFGF­stimulated release of IL­6 in both MC3T3­E1 osteoblastic cells and normal human osteoblasts. Furthermore, VER­155008 significantly enhanced the mRNA expression levels of IL­6 stimulated by bFGF. Western blotting demonstrated a significant increase in the bFGF­stimulated phosphorylation of p38 MAPK in VER­155008­treated MC3T3­E1 cells. A significant increase in the bFGF­stimulated phosphorylation of p38 MAPK was also demonstrated in MC3T3­E1 cells treated with YM­08, another HSP70 inhibitor. VER­155008 or YM­08 did not significantly affect the expression of HSP70 with or without bFGF stimulation. Finally, the specific p38 MAPK inhibitor SB203580 markedly suppressed the enhancing effects of VER­155008 on bFGF­stimulated release of IL­6. Taken together, these results indicated that HSP70 inhibitor amplified bFGF­stimulated release of IL­6 through p38 MAPK activation in the osteoblastic MC3T3­E1 cell line.

Levodopa-Carbidopa Intestinal Gel Injection for Patient with Severe Parkinson's Disease Followed by Total Hip Arthroplasty: A Case Report and Literature Review.

BACKGROUND: Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa-carbidopa intestinal gel (LCIG) infusion. CASE PRESENTATION: The patient is a 59-year-old female with a ten-year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing-off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing-off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing-off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing-off or dyskinesia. The Hoehn-Yahr scale was II in the "on" period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes. CONCLUSION: This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing-off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA.

Resveratrol inhibits basic fibroblast growth factor-induced macrophage colony-stimulating factor synthesis via the PI3-kinase/Akt pathway in osteoblasts.

Resveratrol is a natural polyphenol found in grapes and beneficial for human health. Resveratrol regulates basic fibroblast growth factor (bFGF)-induced osteoprotegerin synthesis through Akt pathway in osteoblast-like MC3T3-E1 cells. In this study, we investigated resveratrol effects on bFGF-induced macrophage colony-stimulating factor (M-CSF) synthesis in MC3T3-E1 cells. bFGF significantly stimulated release and mRNA expression of M-CSF, which was reduced by resveratrol and SRT1720, sirtuin 1 (SIRT1) activator. Inauhzin, SIRT1 inhibitor, reversed inhibitory effects of resveratrol on bFGF-induced mRNA expression of M-CSF. Deguelin, Akt inhibitor, and LY294002, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced bFGF-induced M-CSF synthesis. Inauhzin reversed inhibitory effects of resveratrol on bFGF-induced Akt phosphorylation. Suppressive effect of resveratrol on bFGF-induced osteoprotegerin mRNA expression was confirmed in the identical samples using in experiment of M-CSF mRNA expression. Therefore, resveratrol reduces bFGF-induced M-CSF synthesis in addition to osteoprotegerin synthesis by inhibiting PI3-kinase/Akt pathway and suppressive effects are mediated through SIRT1 activation in osteoblasts.

Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice.

Objective: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL-6) is significantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL-6. Adolescent JIO is particularly challenging to treat and has poor outcome. This study determined if IL-6 receptor blockade prevents bone loss and improves the bone healing in adolescent JIO. Method: Adolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker. Results: Micro-CT assessment showed significantly increased bone volume (p â€‹< â€‹0.001, Cohen's d â€‹= â€‹2.0) and trabecular bone thickness (p â€‹< â€‹0.001, d â€‹= â€‹2.3) after the MR16-1 treatment. Histomorphometric assessment showed significantly increased osteoblast number (p â€‹< â€‹0.01, d â€‹= â€‹2.3), bone formation rate (p â€‹< â€‹0.01, d â€‹= â€‹4.3), and mineral apposition rate (p â€‹< â€‹0.01, d â€‹= â€‹4.1) after the MR16-1 treatment. The number of osteoclasts was unchanged. Histologic assessment showed significantly increased revascularization (p â€‹< â€‹0.01) and restoration of the necrotic marrow with new hematopoietic bone marrow (p â€‹< â€‹0.01). Vascular endothelial growth factor (VEGF) expression was increased in the revascularized area and the articular cartilage, and in the cultured chondrocytes treated with IL-6 receptor inhibitor. Conclusion: IL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO.

A biomechanical analysis of the effect of hydroxyapatite augmentation for trochanteric femoral fractures.

Hydroxyapatite (HA) augments are used to treat trochanteric femoral fractures. However, the efficacy of HA augmentation has not been fully described in trochanteric femoral fracture surgery. In total, 85 patients were enrolled in the present study; all had trochanteric femoral fractures between January 2016 and October 2020, 45 with HA (HA group) and 40 without HA (N group). The intraoperative lag screw insertion torque was directly measured and the amount of lag screw telescoping with and without HA augmentation after surgery was analyzed. Maximum lag screw insertion torque (max-torque), bone mineral density in the opposite femoral neck (n-BMD), tip apex distance (TAD) of the lag screw, radiographic findings including fracture union, the amounts of lag screw telescoping and occurrence of complications were evaluated. A total of 12 patients were excluded if they were aged under 60 years old, had ipsilateral surgery and disorders in the hip joint, TAD of the lag screw ≥26 mm on postoperative radiographs and had measurement errors. A total of 73 fractures could be analyzed: HA group (n=36) and N group (n=37). Max-torque/n-BMD ratios were higher in the HA group compared with in the N group (7.23±2.71 vs. 5.93±1.91 g/cm2·N·m; P=0.04). The amounts of lag screw telescoping in the HA group were smaller compared with the N group (1.41±2.00 vs. 2.58±2.34; P=0.05). Evaluation of screw insertion torque showed maximum screw insertion torque correlated well with n-BMD in both groups, HA (R=0.57; P<0.01) and N group (R=0.64; P<0.01). No correlation was found between maximum screw insertion torque and TAD in both groups, HA (R=-0.10; P=0.62) and N group (R=0.02; P=0.93). All fractures were radiographically united without any complications. These results support the effectiveness of HA augmentation, indicating higher resistance against rotational instability and reduced lag screw telescoping in trochanteric femoral fracture treatment.

Oncostatin M stimulates prostaglandin D2-induced osteoprotegerin and interleukin-6 synthesis in osteoblasts.

Oncostatin M produced by osteal macrophages plays a significant role in fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in bone resorption suppression. Interleukin-6 (IL-6) is a pro-inflammatory cytokine and generally regulates bone resorption. However, accumulating evidence suggests that IL-6 plays pivotal roles in bone formation. We previously showed that prostaglandin D2 (PGD2) induces OPG synthesis by activating p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Furthermore, we demonstrated that PGD2 stimulates IL-6 synthesis by activating p38 MAP kinase and p44/p42 MAP kinase in MC3T3-E1 cells. In the present study, we investigated whether oncostatin M affects PGD2-stimulated OPG and IL-6 synthesis in MC3T3-E1 cells through MAP kinase activation. The osteoblast-like MC3T3-E1 cells and normal human osteoblasts were treated with oncostatin M and subsequently stimulated with PGD2. Consequently, oncostatin M significantly increased the PGD2-stimulated OPG and IL-6 release in both cells. Oncostatin M significantly enhanced mRNA expression levels of OPG and IL-6 induced by PGD2 similarly in both cells. Regarding the signaling mechanism, oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Our results suggest that oncostatin M upregulates the PGD2-stimulated OPG and IL-6 synthesis in osteoblasts and therefore affects bone remodeling. However, OPG and IL-6 synthesis are not mediated through p38 MAP kinase, p44/p42 MAP kinase, or SAPK/JNK pathways.

Pin and Wire System Fixation for the Treatment of Comminuted Patella Fractures.

We describe the wiring technique and evaluate the radiographic and clinical outcomes of treatment with a pin and wire system (PWS) for comminuted patella fractures. From June 2013 to October 2018, 33 patients with comminuted patella fractures were treated using a PWS. Open reduction and internal fixation was performed with multiple pins and a wire. All patients were allowed full weight bearing without a brace. Radiographs were obtained to evaluate bone union, implant breakage, back-out of pins, and intra-articular gaps and step-off. Clinical outcomes and postoperative complications were assessed at final follow-up examination. All fractures were united. Thirteen cable wires in 13 patients were partially broken without displacement of fracture at an average of 7.4 months (range, 1-19 months) postoperatively. The average preoperative, postoperative, and final follow-up intra-articular gap and step-off were 11.7 mm, 0.5 mm, and 0.03 mm and 6.6 mm, 0.4 mm, and 0.2 mm, respectively. The average postoperative pin displacement was 0.1 mm (range, 0-0.8 mm). Deep infection was not observed after the surgery. The implant removal rate was 21% (7 of 33). Among these, the symptomatic implant removal rate was 9% (3 of 33). Additionally, 3 of 7 patients with implant removal had broken wires. The average flexion and extension of knee joints were 139.7° (range, 120°-150°) and -0.9° (range, -10° to 0°), respectively. A PWS prevents back-out of the pins and reduces intra-articular gaps and step-off distances to acceptable levels, even if the cable wire is partially broken. Therefore, a PWS is a good treatment option for comminuted patella fractures. [Orthopedics. 2023;46(5):291-296.].

Fixation of intra-articular calcaneal fractures: A comparative study of the postoperative outcome between HA/PPLA screws and locking plates.

Background: Forged unsintered hydroxyapatite and poly l-lactic acid (F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures. Methods: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed. Results: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50-2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group. Conclusion: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation.

Clinical and radiographic outcomes of primary total hip arthroplasty with the revelation hip system using density mapping.

The Revelation Hip System is a cementless stem with a lateral flare concept. Stable fixation is achieved by fitting the stem to the medullary cavity of the proximal lateral femoral cortex. Patients who have undergone total hip arthroplasty using the Revelation Hip System show good postoperative clinical and radiographic outcomes. However, to the best of our knowledge, no study has reported the relationship between stem fitting and clinical or radiological outcomes after the surgery. In the present study, we investigated the relationship between stem fitting and clinical or radiological outcomes after total hip arthroplasty (THA) using the Revelation Hip System. In this study, 28 hips of 26 patients who were treated with the Revelation Hip System for osteoarthritis, osteonecrosis of the femoral head, rheumatoid arthritis, and rapidly destructive coxarthropathy and were followed up for > 5 y were enrolled. These patients were divided into two groups, including the rest fit group (11 hips, group R) and the control group (17 hips, group C), according to the results of the density mapping analysis. In group R, the lateral side of the stem fits on the medullary cavity of the proximal lateral femoral cortex, while in group C, the lateral side of the stem did not fit. Radiographic results showed no significant differences between the groups in terms of stem alignment, subsidence, and stress shielding around the cup. The incidence of stress shielding around the stem in zone 7 was not significant but tended to be higher in group R than in group C (p = 0.052). Clinical outcomes showed no significant differences between group R and group C in terms of the Harris hip score, the Japanese Orthopaedic Association (JOA) score, and the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) total score. However, pain complaints that were assessed by patient-reported outcomes using the 36-Item Short Form Health Survey (SF-36) bodily pain and vitality subscales and the JHEQ pain subscale were significantly higher in group R than in group C at the final follow-up. These results suggest that some patients had pain complaint even if the stems were inserted as per the concept after THA with the Revelation Hip System.Trial Registration911.

An Analysis of the Femoral Drilling Angle to Avoid Tunnel Collision during Double-Bundle Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction on the Knee.

Concomitant anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction has been reported as an effective technique for providing rotational control of the knee. However, the intraoperative risk of collision with an ACL tunnel during the drilling for the femoral ALL tunnel has been described. The purpose of this study was to investigate the various femoral drilling procedures to avoid tunnel collisions during combined double-bundle ACL and ALL reconstruction. Nine cadaveric knees were used in this study. ACL drilling was performed through the anteromedial portal to footprints of the posterolateral bundle at 120° (PL120) and 135° (PL135) knee flexion and the anteromedial bundle at 120° (AM120) and 135° (AM135) knee flexion. ALL drilling was performed at 0° (Cor0-ALL) and 30° (Cor30-ALL) coronal angles using a Kirschner wire (K-wire). The distance between the ALL footprint and ACL K-wire outlets, axial angles of ALL K-wires colliding with ACL K-wires, and distances from the ALL footprint to the collision point were measured. From these values, the safe zone, defined as the range of axial angles in which no collisions or penetrations occurred, was identified by simulation of tunnels utilized for reconstruction grafts in each drilling procedure. The point-to-point distance from the ALL footprint to the K-wire outlet was significantly greater in the AM120 than the AM135 (13.5 ± 3.1, 10.8 ± 3.2 mm; p = 0.048) and in the PL135 than the PL120 (18.3 ± 5.5, 16.1 ± 6.5 mm; p = 0.005) conditions, respectively. During an ACL drilling combination of PL135/AM120, a safe zone of > 45° in Cor30-ALL was identified. With a narrow safe zone during the PL135/AM120 combination only, the risk of femoral tunnel collisions in combined double-bundle ACL and ALL reconstruction is high. AM drilling at 120° and PL drilling at > 135° knee flexion, combined with ALL drilling at 30° coronal angle and > 45° axial angle, may reduce this risk.

Oncostatin M attenuates tumor necrosis factor-α-induced synthesis of macrophage-colony stimulating factor via suppression of Akt in osteoblasts.

BACKGROUND: Oncostatin M produced by osteal macrophages, a cytokine that belongs to the interleukin-6 family, is implicated in bone fracture healing. Macrophage colony-stimulating factor (M-CSF) secreted from osteoblasts plays an important role in osteoclastogenesis. We have previously reported that tumor necrosis factor-α (TNF-α), a potent bone resorptive agent, stimulates the activation of p44/p42 mitogen-activated protein (MAP) kinase, Akt, and p70 S6 kinase in osteoblast-like MC3T3-E1 cells, and induces the synthesis of M-CSF at least in part via Akt. OBJECTIVE: In the present study, we investigated whether oncostatin M affects the TNF-α-induced M-CSF synthesis in MC3T3-E1 cells and the underlying mechanisms. METHODS: Clonal osteoblast-like MC3T3-E1 cells were treated with oncostatin M or rapamycin and then stimulated with TNF-α. M-CSF release was assessed by ELISA. M-CSF mRNA expression level was assessed by real-time RT-PCR. Phosphorylation of Akt, p44/p42 MAP kinase, and p70 S6 kinase was detected by Western blot analysis. RESULTS: Oncostatin M dose-dependently reduced the TNF-α-stimulated M-CSF release. The expression of M-CSF mRNA induced by TNF-α was significantly suppressed by oncostatin M. Rapamycin, an inhibitor of mTOR/p70 S6 kinase, had little effect on the M-CSF release by TNF-α. Oncostatin M significantly reduced the TNF-α-induced phosphorylation of Akt and p44/p42 MAP kinase. However, the p70 S6 kinase phosphorylation by TNF-α was not affected by oncostatin M. CONCLUSION: These results strongly suggest that oncostatin M attenuates TNF-α-stimulated synthesis of M-CSF in osteoblasts, and the inhibitory effect is exerted at a point upstream of Akt and p44/p42 MAP kinase but not p70 S6 kinase.

HSP70 inhibitors upregulate prostaglandin E1-induced synthesis of interleukin-6 in osteoblasts.

Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors-VER-155008 and YM-08-, PD98059, SB203580 or SP600125 and then stimulated with PGE1. IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE1-stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE1-stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE1-stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE1-stimulated IL-6 release. YM-08 stimulated the PGE1-induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE1-stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE1-stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling.

Evaluation of lower extremity gait analysis using Kinect V2® tracking system.

INTRODUCTION: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. METHODS: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson's correlation and overall agreement with a method of meta-analysis of Pearson's correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. RESULTS: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. CONCLUSIONS: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

Upregulation of TGF-ß-induced HSP27 by HSP90 inhibitors in osteoblasts.

BACKGROUND: Heat shock protein (HSP) 90 functions as a molecular chaperone and is constitutively expressed and induced in response to stress in many cell types. We have previously demonstrated that transforming growth factor-ß (TGF-ß), the most abundant cytokine in bone cells, induces the expression of HSP27 through Smad2, p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in mouse osteoblastic MC3T3-E1 cells. This study investigated the effects of HSP90 on the TGF-ß-induced HSP27 expression and the underlying mechanism in mouse osteoblastic MC3T3-E1 cells. METHODS: Clonal osteoblastic MC3T3-E1 cells were treated with the HSP90 inhibitors and then stimulated with TGF-ß. HSP27 expression and the phosphorylation of Smad2, p44/p42 MAPK, p38 MAPK, and SAPK/JNK were evaluated by western blot analysis. RESULT: HSP90 inhibitors 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib significantly enhanced the TGF-ß-induced HSP27 expression. TGF-ß inhibitor SB431542 reduced the enhancement by 17-DMAG or onalespib of the TGF-ß-induced HSP27 expression levels. HSP90 inhibitors, geldanamycin, onalespib, and 17-DMAG did not affect the TGF-ß-stimulated phosphorylation of Smad2. Geldanamycin did not affect the TGF-ß-stimulated phosphorylation of p44/p42 MAPK or p38 MAPK but significantly enhanced the TGF-ß-stimulated phosphorylation of SAPK/JNK. Onalespib also increased the TGF-ß-stimulated phosphorylation of SAPK/JNK. Furthermore, SP600125, a specific inhibitor for SAPK/JNK, significantly suppressed onalespib or geldanamycin's enhancing effect of the TGF-ß-induced HSP27 expression levels. CONCLUSION: Our results strongly suggest that HSP90 inhibitors upregulated the TGF-ß-induced HSP27 expression and that these effects of HSP90 inhibitors were mediated through SAPK/JNK pathway in osteoblasts.

Incretins Enhance PGF2α-Induced Synthesis of IL-6 and Osteoprotegerin in Osteoblasts.

Incretins including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine after oral food ingestion, are currently well-known to stimulate insulin secretion from pancreatic ß-cells and used for the treatment of type 2 diabetes mellitus. We have previously reported that prostaglandin F2α (PGF2α) stimulates the synthesis of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells, and that IL-6 and osteoprotegerin release are mediated through the p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways. In the present study, we investigated the effects of incretins including GLP-1 and GIP, on the PGF2α-induced synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly stimulated the PGF2α-induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF2α-induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF2α-induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF2α was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF2α-induced synthesis of IL-6 and osteoprotegerin in osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways.