Bisphosphonates play an important role in the treatment of catabolic bone diseases such as osteoporosis. In addition to their anti-resorptive activity exerted by their proapoptotic effect on osteoclasts, recent data suggest that nitrogen-containing bisphosphonates (N-BP) may also promote osteogenic differentiation by an unknown mechanism. Similar bone-anabolic effects have been attributed to cholesterol-lowering statins, which represent another class of mevalonate pathway inhibitors besides N-BP, suggesting a common mode of action. In vascular endothelial cells statins were recently shown to activate the Mek5/Erk5 mitogen-activated protein kinase cascade, which plays an important role in cellular differentiation, apoptosis or inflammatory processes. Here we evaluated whether N-BPs may also target the Mek5/Erk5 pathway and analysed the consequence of Erk5 activation on bone-relevant gene expression, calcification and osteoblast differentiation. We show that N-BP dose-dependently activate Erk5 in primary human endothelial cells and osteoblasts. The mechanism likely involves farnesyldiphosphate synthase (FDPS) inhibition and subsequent inactivation of the small GTPase Cdc42 since siRNA-mediated knockdown of both genes could reproduce N-BP-induced ERK5 activation. ERK5 activation resulted in regulation of several bone-relevant genes and was required for calcification and osteoblastic differentiation of mesenchymal stems cells as evident by the lack of alkaline phosphatase induction and alizarin-red staining observed upon Erk5 knockdown or upon differentiation initiation in presence of a pharmacological Erk5 inhibitor.Background/Aims
Methods and Results
The additive use of an external modular device may improve dorsal compression forces in pelvic external fixation. This would improve the efficiency of indirect reduction and stabilization with an anterior pelvic external fixator. The purpose of this study was to determine the forces of the posterior pelvis achieved by a new device improving the application of a supraacetabular anterior external fixator compared with other constructs. Synthetic pelvic models were used. Complete pelvic ring instability was created by symphyseal and unilateral sacroiliac joint disruption. Four different constructs of fixation were tested. A pressure-sensitive film was placed in the sacroiliac joint. The constructs were applied in a standardized way. The maximum sacroiliacal compression loads (N) of each trial was recorded. Statistics was performed with the student t-test.Objectives
Material and Method
Previous fluoroscopic analyses of Total Hip Arthroplasty (THA) determined that the femoral head slides within the acetabular cup, leading to separation of certain aspects of the articular geometries. Although separation has been well documented, it has not been correlated to clinical complications or a more indepth understanding of the cause and effect. Surgical technique is one of the important clinical factors when considering THA procedures, and it is hypothesized, that it could affect the magnitude and occurrence of femoral head separation (sliding) in THAs. Hence, the objective of this study was to determine and compare in-vivo THA kinematics for subjects implanted with a THA using two different surgical approaches. Thirty seven subjects, each implanted with one of two types of THA were analysed under in vivo, weight-bearing conditions using video fluoroscopy while performing a sit-to-stand activity. Ten subjects were implanted by Surgeon 1 using a long incision postero-lateral approach (G1); while a further 10 subjects were implanted by the same surgeon using a short incision posterolateral approach (G2). The remaining 17 subjects were implanted using the anterolateral approach; 10 by Surgeon 2 (G3) and seven by Surgeon 3 (G4). All patients with excellent clinical results, without pain or functional deficits were invited to participate in the study (HHS >
90). 3D kinematics of the hip joint was determined, with the help of a previously published 2D-to-3D registration technique. From a completely seated position to the standing position, four frames of the fluoroscopy video were analysed. Subjects in all groups experienced some degree of femoral head separation at all increments of the sit-to-stand activity that were analysed. The magnitude and frequency of separation greater than 1.0mm varied between each surgeon group, between incision types, between incision lengths and between the two types of THA that were analysed. The average maximum separation was 1.3, 1.1, 1.3 and 1.4mm for G1, G2, G3 and G4 respectively. Though there was no difference in the average maximum separation values for the 4 groups, the maimum separation varied significantly. While the maximum separation in G2 was 1.8mm, the maximum separation in G4 was 3.0mm. G1 and G3 had maximum separation values of 2.3mm and 2.4mm respectively. This study suggests that there may be a correlation between incision lengths and surgical approach with femoral head separation in THAs. The maximum separation that was seen among all groups was a subject with a traditional long incision, while the short incision group had less incidence of separation. Results from this study may give researchers and implant developers a better understanding of kinematics around the hip joint and how they vary with respect to different surgical techniques. Further analysis is being conducted on the subjects before definitive conclusions can be made.
This research is to relate functional outcomes to kinematics in high flexion CR and PS total knees by using the Total Knee Function Questionnaire in patients who had previously undergone kinematic analyses. Patients were identified who had primary total knee arthroplasty and had undergone kinematic analyses using fluoroscopy. The Total Knee Function Questionnaire was sent to these patients, and data was obtained for 14 CR knees (NexGen CR-Flex, Zimmer) and for 13 PS knees (Legacy LPS-Flex, Zimmer). The questionnaire evaluates baseline activities of daily living, advanced activities, and recreational activities and exercises. CR patients reported higher satisfaction and that their knees felt more “normal” than PS patients. Some baseline activity scores were significantly higher for CR than for PS knees. Limitations in baseline activities were related to kinematic constraints, including flexion, lateral and medial anterior-posterior (A-P) translations, and tibiofemoral axial rotation. Kinematic data were related to difficulty data for advanced and recreational activities of kneeling, squatting, gardening, and stretching. Comparisons between kinematic data and patient feedback on knee function provided unique information about differences between CR and PS high flexion implants. CR patients had better function than PS patients in walking on even ground or uphill or sitting. CR patients had higher activity scores for recreational than for advanced activities, while activity scores for the PS patients were similar between these activities. Kinematic variables that affected function for some activities included extremes of flexion, A-P translations of lateral and medial condyles, and axial rotation intervals.
Compared to conventional road-cycling, little is known about overuse injuries in mountainbiking. The adjustment of the mountainbike seems to be crucial avoiding these syndromes. No other study has prospectively put overuse injuries into correlation with the mountainbike’s adjustment in a competition setting until now.
Treatments of complex foot deformities often need use of special external fixators to treat various deformities of multiplaner directions and contractures of ankle and foot joints. In severe cases the best choice is use external hinge distraction system to restore function of joints, treat short foot, and correct deformity. Simple, small, mobile hinges/SLDF 2/was modified for the treatment. From 1995 to 2007 we treated 160 cases to severe foot deformities with congenital clubfoot, neuromuscular deformities and posttraumatic deformities age between 3 to 60 years with the new modified system. In some cases the treatment was combined with lengthening and axial correction of the lower leg if needed. The average time for correction is 4 to 6 week’s followings by 1–3 months of fixation to keep the final correction. A special orthosis is needed after removal of the fixation devices for another 6 months. Complications were mostly superficial Pin infection, loosening of wires, no nerve or vascular damage and no thrombosis was seen. In all cases a plantigrade foot was achieved with some stiffness of the joints in neuromuscular diseases. The walking ability was in most cases much better due to plantigrade correction; enable the patient to walk without any aid accept orthopedic shoes. The satisfaction rate of all patients was very good; some of the patients were abele to wake first time due to the correction. The use of external fixation is an ideal treatment in complex congenital or posttraumatic foot deformities to achieve good correction, good functional and cosmetic result with a tolerable system.