An LGR4 agonist activates the GSK­3ß pathway to inhibit RANK­RANKL signaling during osteoclastogenesis in bone marrow­derived macrophages.

The binding between receptor­activated nuclear factor­κB (RANK) and the RANK ligand (RANKL) during osteoclast development is an important target for drugs that treat osteoporosis. The leucine­rich repeat­containing G­protein­coupled receptor 4 (LGR4) acts as a negative regulator of RANK­RANKL that suppresses canonical RANK signaling during osteoclast differentiation. Therefore, LGR4 agonists may be useful in inhibiting osteoclastogenesis and effectively treating osteoporosis. In the present study, bone marrow­derived macrophages and a mouse model of RANKL­induced bone loss were used to investigate the effect of mutant RANKL (MT RANKL), which was previously developed based on the crystal structure of the RANKL complex. In the present study, the binding affinity of wild­type (WT) RANKL and MT RANKL to RANK and LGR4 was determined using microscale thermophoresis analysis, and the effect of the ligands on the AKT­glycogen synthase kinase­3ß (GSK­3ß)­nuclear factor of activated T cells, cytoplasmic, calcineurin­dependent 1 (NFATc1) signaling cascade was investigated using western blotting and confocal microscopy. In addition, the expression of LGR4 and the colocalization of LGR4 with MT RANKL were analyzed in a mouse model of RANKL­induced bone loss. The results showed that in osteoclast precursor cells, MT RANKL bound with high affinity to LGR4 and increased GSK­3ß phosphorylation independently of AKT, resulting in the inhibition of NFATc1 nuclear translocation. In the mouse model, MT RANKL colocalized with LGR4 and inhibited bone resorption. These results indicated that MT RANKL may inhibit RANKL­induced osteoclastogenesis through an LGR4­dependent pathway and this could be exploited to develop new therapies for osteoporosis.

Femoral head cartilage reconstruction using autologous osteochondral mosaicplasty: A case report.

RATIONALE: Cartilage injuries of the femoral head may occur following hip dislocation. As a rare injury, controversy persists regarding ideal treatment of damaged femoral head cartilage. Here we report the case of a patient who developed a large cartilage injury to the femoral head following anterior hip dislocation for which autologous osteochondral mosaicplasty with a graft harvested from the ipsilateral femoral head achieved a satisfactory outcome. PATIENT CONCERNS: A 62-year-old man developed a right hip dislocation after a fall from a 5-m height and was referred to our institution. DIAGNOSES: The initial diagnosis was anterior hip dislocation. Upon hip joint reduction, a simple radiograph and computed tomography scan showed a large cartilage defect in the superolateral region of the femoral head. Multiple bony fragments were visible within the joint. INTERVENTIONS: The hip joint was surgically dislocated. The large cartilage defect of the femoral head was treated with autologous mosaicplasty using an osteochondral autograft transfer system using multiple osteochondral plugs retrieved from a non-weight-bearing portion of the ipsilateral femoral head. OUTCOMES: Diagnostic hip arthroscopy performed at 8 months postoperative confirmed full incorporation of the osteochondral graft into the native femoral head. At the 2-year follow-up, the patient was pain-free, had a normal range of motion and displayed no evidence of osteoarthritis. LESSONS: Isolated femoral head cartilage injuries may occur as a consequence of anterior hip dislocation. A femoral head with a large irregular cartilage defect can be treated with mosaicplasty using an osteochondral autograft from a non-weight-bearing portion of the ipsilateral femoral head.

Biomechanical analysis analyzing association between bone mineral density and lag screw migration.

A proximal femoral nail using a helical blade (HB) is commonly utilized to treat proximal femoral fracture but cut through failure of the lag screws is one of the devastating complications following the surgery. While controversial, one of the potential risk factors for cut through failure is poor bone strength which can be predicted by measuring bone mineral density (BMD). In this study, we performed a biomechanical test on the fractured femoral head to validate whether the indirectly measured BMD from the contralateral hip or that measured directly from the retrieved femoral head can elucidate the structural strength of the fractured femoral head and thereby can be used to predict migration of lag screws. Our result showed that directly measured BMD has a significant correlation with the HB migration on the osteoporotic femoral head. However, while the BMDs measured from the contralateral femoral neck or total hip is the most widely used parameter to predict the bone strength of the fractured femur, this may have limited usability to predict HB migration.

Comparison of Helical Blade Systems for Osteoporotic Intertrochanteric Fractures Using Biomechanical Analysis and Clinical Assessments.

Background and Objectives: This study aimed to compare the biomechanical properties and outcomes of osteoporotic intertrochanteric fractures treated with two different helical blade systems, the trochanteric fixation nail-advanced (TFNA) and proximal femoral nail antirotation II (PFNA), to evaluate the efficacy and safety of the newly introduced TFNA system. Materials and Methods: A biomechanical comparison of the two helical blades was performed using uniaxial compression tests on polyurethane foam blocks of different densities. The peak resistance (PR) and accumulated resistance (AR) were measured during the 20 mm advancement through the test block. For clinical comparison, 63 osteoporotic intertrochanteric fractures treated with TFNA were identified and compared with the same number of fractures treated with PFNA using propensity score matching. Ambulatory status, medial migration, lateral sliding, fixation failure, and patient-reported outcomes were compared between the two groups over a minimum of 1 year's follow up. Results: The uniaxial compression test showed that a slightly, but significantly lower resistance was required to advance the TFNA through the test block compared with the PFNA (20 PCF, p = 0.017 and p = 0.026; 30 PCF, p = 0.007 and p = 0.001 for PR and AR, respectively). Clinically, the two groups showed no significant differences in post-operative ambulatory status and patient-reported outcomes. However, in TFNA groups, significantly more medial migration (TFNA, 0.75 mm; PFNA, 0.40 mm; p = 0.0028) and also, lateral sliding was noted (TFNA, 3.99 mm; PFNA, 1.80 mm; p = 0.004). Surgical failure occurred in four and two fractures treated with the TFNA and PFNA, respectively. Conclusions: The results of our study suggest that the newly introduced TFNA provides clinical outcomes comparable with those of the PFNA. However, inferior resistance to medial migration in the TFNA raises concerns regarding potential fixation failures.

Impact of Capsulotomy on Hip Biomechanics during Arthroscopy.

Background and Objectives: Anterior capsulotomy is routinely performed in hip arthroscopy to improve joint visualization; however, this can partly or completely disrupt the stabilizing ligaments of the hip. This study aimed to report the effects of conventional and extensive arthroscopic capsulotomies on hip stability. Materials and Methods: Eight freshly frozen cadaveric pelvises were used in this study. The range of motion and translation were measured and compared among different capsular conditions utilized in hip arthroscopy, with a special interest in the iliofemoral ligament (IFL) and zona orbicularis (ZO). The conditions included intact capsule, interportal capsulotomy, T-capsulotomy, complete IFL disruption, and complete IFL and ZO disruption. Internal rotation at three flexion planes (-10°, 0°, and 30°) and external rotation at six flexion planes (-10°, 0°, 30°, 60°, 90°, and 110°) were measured with corresponding femoral head translation distance at the application of 2.5 Nm torque. Results: As compared to an intact capsule, a significant increase in external rotation was observed after interportal capsulotomy from -10° to 60° and after T-capsulotomy from -10° to 110° flexion. A significant translation was observed only with a T-capsulotomy, which ranged from 1.9 to 2.3 mm across the flexion angles. Compared with conventional interportal capsulotomy, disruption of the entire IFL resulted in a significant increase in external rotation in all flexion planes, and significant translation was accompanied by disruption of the ZO. Conclusions: Interportal capsulotomy can result in an increase in range of motion, and T-capsulotomy can lead to significant translation. Partial or complete tears of the IFL and ZO can result in further external rotation and translation.

Correction to: Implications of the Overlapping Degree Between Proximal Fibula and Tibia for Placing the Optimal Syndesmotic Screw: A Virtual Cadaveric Study.

[This corrects the article DOI: 10.1007/s43465-021-00437-y.].

Implications of the Overlapping Degree Between Proximal Fibula and Tibia for Placing the Optimal Syndesmotic Screw: A Virtual Cadaveric Study.

BACKGROUND: To determine the optimal direction of the syndesmotic screw and to introduce a consistent landmark for practical application by analyzing three-dimensional (3D) modeling and virtual implantation. METHODS: A total of 105 cadaveric lower legs (50 males and 55 females; average height, 160.6 ± 7.1 cm) were used to reconstruct a 3D model by using the Mimics® software and the joint morphology was evaluated. Syndesmotic cylinders (Ø3.5 mm/Length 100 mm) were transversely placed in the proximal end of the incisura fibularis for simulating screw fixation. The tibial proximal cylinder, which was tangent to the posterior tibial condyles, was traced and the angle between the two cylinders was measured as the tibial torsion angle (TTA). After rotating the syndesmotic cylinder parallel to the ground, the overlapping degree between the proximal fibula and tibia was assessed as a radiologic indicator. RESULTS: Concerning tibial torsion, the TTA was an average of 36.7° (range, 17.2°-54.4°; SD, 8.78) When the syndesmotic cylinder was rotated to be parallel to the ground, the proximal fibula had nonlinear or linear overlap with the lateral border of the tibia, regardless of the joint morphology. In this non-overlapping view, three Weber's indices for normal fibular length could be better visualized than the mortise view. CONCLUSION: The syndesmotic cylinder in the proximal end of the incisura fibularis could be consistently placed parallel to the ground by internally rotating the tibia until there was a nonlinear or linear overlap between the proximal fibula and the tibia, regardless of the joint morphology.

Application of Multi-Layered Temperature-Responsive Polymer Brushes Coating on Titanium Surface to Inhibit Biofilm Associated Infection in Orthopedic Surgery.

Infection associated with biomedical implants remains the main cause of failure, leading to reoperation after orthopedic surgery. Orthopedic infections are characterized by microbial biofilm formation on the implant surface, which makes it challenging to diagnose and treat. One potential method to prevent and treat such complications is to deliver a sufficient dose of antibiotics at the onset of infection. This strategy can be realized by coating the implant with thermoregulatory polymers and triggering the release of antibiotics during the acute phase of infection. We developed a multi-layered temperature-responsive polymer brush (MLTRPB) coating that can release antibiotics once the temperature reaches a lower critical solution temperature (LCST). The coating system was developed using copolymers composed of diethylene glycol methyl ether methacrylate and 2-hydroxyethyl methacrylate by alternatively fabricating monomers layer by layer on the titanium surface. LCST was set to the temperature of 38-40 °C, a local temperature that can be reached during infection. The antibiotic elution characteristics were investigated, and the antimicrobial efficacy was tested against S. aureus species (Xen29 ATCC 29 213) using one to four layers of MLTRPB. Both in vitro and in vivo assessments demonstrated preventive effects when more than four layers of the coating were applied, ensuring promising antibacterial effects of the MLTRPB coating.