Non-operative treatment of unicompartmental osteoarthritis of the knee: a prospective randomized trial with two different braces-ankle-foot orthosis versus knee unloader brace.

BACKGROUND: The use of an unloader brace is a non-surgical treatment option for patients with medial osteoarthritis (OA). However, many patients do not adhere to brace treatment, because of skin irritation due to the pads at the level of the joint space and bad fit. A new concept to unload the medial compartment of the knee is a foot ankle brace with a lever arm pressing the thigh in valgus. The aim of this prospective randomized trial was to examine the outcomes of patients with medial OA after treatment with a conventional knee unloader brace (Unloader One®) and the new foot ankle orthosis (Agilium FreeStep®). METHODS: For this multicenter trial, 160 patients (> 35 years) with medial OA were randomly allocated to treatment with a conventional knee unloader brace (Unloader One®) or treatment with the new knee OA ankle brace (Agilium FreeStep®). The primary outcome measure was pain (numerical analog scale) at baseline (T0), 8 weeks (T1), and 6 months (T2). Secondary outcome measures were knee function (Knee Injury and Osteoarthritis Outcome Score, KOOS), side effects, additional interventions, and compliance. RESULTS: In both groups, walking pain improved between T0 and T1 and also between T0 and T2 without a significant group difference. For pain at sports, both groups showed a significant improvement between T0 and T2 without a significant group difference. The KOOS subscales symptoms, pain, activity, sport, and quality of life increased significantly in both treatment groups without any significant group differences at T 0, T1, and T2. There was also no significant group difference in additional interventions and weekly or daily brace use. In the Agilium FreeStep® group (23.5%), significantly less patients reported bruises in contrast to the Unloader One® group (66.7%). DISCUSSION: The results of this clinical trial show that the foot ankle brace is as effective as a conventional knee unloader brace for the treatment of medial knee OA with regard to clinical outcome. The rate of side effects such as bruises was significantly lower in the Agilium FreeStep® group. TRIAL REGISTRATION: DRKS00009215, 13.8.2015.

Biomechanical effect of unloader braces for medial osteoarthritis of the knee: a systematic review (CRD 42015026136).

PURPOSE: There is a lack of consensus regarding biomechanical effects of unloader braces for the treatment of medial osteoarthritis (OA) of the knee. The purpose of this study was to perform a systematic review of studies examining the biomechanical effect of unloader braces. METHODS: A systematic search for articles about the biomechanical effect of unloader braces was performed. Primary outcome measure was the influence of the brace on the knee adduction moment. Data sources were Pubmed central and google scholar. RESULTS: Twenty-four articles were included. Twenty articles showed that valgus unloader braces significantly decrease the knee adduction moment. Seven of those studies reported a decrease of pain in braced patients (secondary outcome measure). Positive effects on the knee adduction moment could be found for custom made braces for conventional knee braces and for a foot ankle orthosis. Four studies could not show any effect of knee unloader braces on the knee adduction moment although one of these studies found decreased pain in braced patients. One of these studies examined healthy patients with a neutral axis. CONCLUSION: This systematic review could demonstrate evidence that unloader braces reduce the adduction moment of the knee. Foresighted, a systematic review about the clinical effect of unloader braces is required.

Evaluating the potential synergistic benefit of a realignment brace on patients receiving exercise therapy for patellofemoral pain syndrome: a randomized clinical trial.

BACKGROUND: It has been previously shown that exercise programs for patellofemoral pain syndrome (PFPS) can be supported by medially directed taping. Evidence supporting the use of patellar braces is limited because previous studies have been low quality. The aim of this study is to compare the outcomes of patients with PFPS after treatment with a medially directed patellar realignment brace and supervised exercise. METHODS: In a prospective randomized multicenter trial, 156 patients with PFPS were included and randomly assigned to 6 weeks of supervised physiotherapy in combination with the patellar realignment brace, or supervised physiotherapy alone. Outcome measures were the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, numeric analog pain scores, and the Kujala score at baseline, 6 weeks, 3 months, and 1 year after the start of therapy. The patient's self-reported perception of recovery was also assessed at these points. RESULTS: Both treatment groups showed a significant improvement in all outcome measures over the study period. After 6 and 12 weeks of therapy, patients in the brace group had significantly higher KOOS sub-scale scores, a higher mean Kujala score, and less pain while climbing stairs or playing sports. After 54 weeks a group difference could be only detected for the KOOS ADL sub-scale. CONCLUSION: The use of a medially directed realignment brace leads to better outcomes in patients with PFPS than exercise alone after 6 and 12 weeks of treatment. After 1 year of follow-up this positive effect diminished.

Early functional outcome of two different orthotic concepts in ankle sprains: a randomized controlled trial.

INTRODUCTION: Purpose of the study was the evaluation of the early functional outcome of patients with an acute ankle sprain treated either with a semirigid, variable, phase-adapted modular ankle orthosis or an invariable orthotic reference device. MATERIALS AND METHODS: Forty-seven patients with acute ankle sprain grade II or more were included. In addition, 77 healthy controls as a reference were investigated. The injured subjects were treated with one of the two devices by random for 6 weeks. Ankle scores (FAOS, AOFAS) were taken at baseline after injury, 1 and 3 months after injury. Functional performance tests (balance platform, zig zag run, shuttle run, vertical drop jump) were performed at 1 and 3 months after injury. RESULTS: No significant score differences could be found between the two intervention groups except for achieving a preinjury activity level after 3 months only in the modular orthosis group. Postural functional performances (balance test) also showed no significant differences whereas the results of the agility tests revealed small but significant better results in the modular orthosis group in comparison to the invariable orthosis group. Cohen's effect sizes were high. CONCLUSION: Differences between the two intervention groups were marginal and very small but significant and--regarding Cohen's effect sizes--effective. Especially relating to functional performance, this might be a careful indication that a more effective strategy for promoting a protected, rapid recovery to physical activity after ankle sprains might be achieved by applying a phase-adapted ankle orthosis. Especially in athletic patients, phase-adapted orthosis should be further investigated and considered to ensure fully protected ligament healing as well as to regain early functional recovery.

The Patella Pro study - effect of a knee brace on patellofemoral pain syndrome: design of a randomized clinical trial (DRKS-ID:DRKS00003291).

BACKGROUND: Patellofemoral pain syndrome (PFPS) is a frequent cause of anterior knee pain predominantly affecting young female patients who do not have significant chondral damage. Development of PFPS is probably multifactorial, involving various knee, hip, and foot kinematic factors. Biomechanical studies have described patellar maltracking and dynamic valgus (functional malalignment) in patients with patellofemoral pain syndrome. The literature provides evidence for short-term use of nonsteroidal anti-inflammatory drugs; short-term medially directed taping; and exercise programs focusing on the lower extremity, hip, and trunk muscles. Evidence supporting the use of patellar braces is limited because previous studies have been low quality. The aim of this article is to publish the design of a prospective randomized trial that examines the outcomes of patients with PFPS after treatment with a new patellar brace (Patella Pro) that applies medially directed force on the patella. METHODS/DESIGN: For this multicenter trial, 156 patients (adolescents and young adults) with PFPS were recruited from orthopedic practices and orthopedic hospitals and randomly allocated to 3 months of supervised physiotherapy in combination with the Patella Pro brace or supervised physiotherapy alone. The primary outcome measures are pain (numerical analog scale); knee function (Kujala score and Knee Injury and Osteoarthritis Outcome Score); and self-reported perception of recovery at baseline, 6 weeks, 3 months, and 1 year. DISCUSSION: Only limited evidence for the use of a patellar brace for the treatment of PFPS exists in the literature. Disputable evidence for the use of orthoses for PFPS patients has been presented in one meta-analysis, in which only one of three studies found the effect of a medially directed patellar brace to be significant. Because of these low-quality studies, the authors concluded that this evidence should be regarded as limited, and we feel there is a need for further well-designed studies to evaluate the effect of patellar bracing on PFPS-related pain. The Patella Pro study is a prospective randomized trial in which supervised physiotherapy in combination with a patellar brace is compared with supervised physiotherapy alone. This trial started in April 2012 and finished in October 2013. TRIAL REGISTRATION: DRKS-ID:DRKS00003291, January 3rd, 2012.

Patellofemoral pain syndrome.

UNLABELLED: The patellofemoral pain syndrome (PFPS) is a possible cause for anterior knee pain, which predominantly affects young female patients without any structural changes such as increased Q-angle or significant chondral damage. This literature review has shown that PFPS development is probably multifactorial with various functional disorders of the lower extremity. Biomechanical studies described patellar maltracking and dynamic valgus in PFPS patients (functional malalignment). Causes for the dynamic valgus may be decreased strength of the hip abductors or abnormal rear-foot eversion with pes pronatus valgus. PFPS is further associated with vastus medialis/vastus lateralis dysbalance, hamstring tightness or iliotibial tract tightness. The literature provides evidence for a multimodal non-operative therapy concept with short-term use of NSAIDs, short-term use of a medially directed tape and exercise programmes with the inclusion of the lower extremity, and hip and trunk muscles. There is also evidence for the use of patellar braces and foot orthosis. A randomized controlled trial has shown that arthroscopy is not the treatment of choice for treatment of PFPS without any structural changes. Patients with anterior knee pain have to be examined carefully with regard to functional causes for a PFPS. The treatment of PFPS patients is non-operative and should address the functional causes. LEVEL OF EVIDENCE: V.

Anterior knee pain after total knee arthroplasty: a narrative review.

Anterior knee pain is one of the most common causes of persistent problems after implantation of a total knee replacement. It can occur in patients with or without patellar resurfacing. As a result of the surgical procedure itself many changes can occur which may affect the delicate interplay of the joint partners in the patello-femoral joint. Functional causes of anterior knee pain can be distinguished from mechanical causes. The functional causes concern disorders of inter- and intramuscular coordination, which can be attributed to preoperative osteoarthritis. Research about anterior knee pain has shown that not only the thigh muscles but also the hip and trunk stabilising muscles may be responsible for the development of a dynamic valgus malalignment. Dynamic valgus may be a causative factor for patellar maltracking. The mechanical causes of patello-femoral problems after knee replacement can be distinguished according to whether they increase instability in the joint, increase joint pressure or whether they affect the muscular lever arms. These causes include offset errors, oversizing, rotational errors of femoral or tibial component, instability, maltracking and chondrolysis, patella baja and aseptic loosening. In these cases, reoperation or revision is often necessary.

Treatment of acute ankle ligament injuries: a systematic review.

BACKGROUND: Lateral ankle sprains are common musculoskeletal injuries. OBJECTIVES: The objective of this study was to perform a systematic literature review of the last 10 years regarding evidence for the treatment and prevention of lateral ankle sprains. DATA SOURCE: Pubmed central, Google scholar. STUDY ELIGIBILITY CRITERIA: Meta-analysis, prospective randomized trials, English language articles. INTERVENTIONS: Surgical and non-surgical treatment, immobilization versus functional treatment, different external supports, balance training for rehabilitation, balance training for prevention, braces for prevention. METHODS: A systematic search for articles about the treatment of lateral ankle sprains that were published between January 2002 and December 2012. RESULTS: Three meta-analysis and 19 articles reporting 16 prospective randomized trials could be identified. The main advantage of surgical ankle ligament repair is that objective instability and recurrence rate is less common when compared with non-operative treatment. Balancing the advantages and disadvantages of surgical and non-surgical treatment, we conclude that the majority of grades I, II and III lateral ankle ligament ruptures can be managed without surgery. For non-surgical treatment, long-term immobilization should be avoided. For grade III injuries, however, a short period of immobilization (max. 10 days) in a below knee cast was shown to be advantageous. After this phase, the ankle is most effectively protected against inversion by a semi-rigid ankle brace. Even grades I and II injuries are most effectively treated with a semi-rigid ankle brace. There is evidence that treatment of acute ankle sprains should be supported by a neuromuscular training. Balance training is also effective for the prevention of ankle sprains in athletes with the previous sprains. There is good evidence from high level randomized trials in the literature that the use of a brace is effective for the prevention of ankle sprains. CONCLUSION: Balancing the advantages and disadvantages of surgical and non-surgical treatment, we conclude that the majority of grades I, II and III lateral ankle ligament ruptures can be managed without surgery. The indication for surgical repair should be always made on an individual basis. This systematic review supports a phase adapted non-surgical treatment of acute ankle sprains with a short-term immobilization for grade III injuries followed by a semi-rigid brace. More prospective randomized studies with a longer follow-up are needed to find out what type of non-surgical treatment has the lowest re-sprain rate.

Patellofemoral pain in athletes.

Patellofemoral pain (PFP) is a frequent cause of anterior knee pain in athletes, which affects patients with and without structural patellofemoral joint (PFJ) damage. Most younger patients do not have any structural changes to the PFJ, such as an increased Q angle and a cartilage damage. This clinical entity is known as patellofemoral pain syndrome (PFPS). Older patients usually present with signs of patellofemoral osteoarthritis (PFOA). A key factor in PFPS development is dynamic valgus of the lower extremity, which leads to lateral patellar maltracking. Causes of dynamic valgus include weak hip muscles and rearfoot eversion with pes pronatus valgus. These factors can also be observed in patients with PFOA. The available evidence suggests that patients with PFP are best managed with a tailored, multimodal, nonoperative treatment program that includes short-term pain relief with nonsteroidal anti-inflammatory drugs (NSAIDs), passive correction of patellar maltracking with medially directed tape or braces, correction of the dynamic valgus with exercise programs that target the muscles of the lower extremity, hip, and trunk, and the use of foot orthoses in patients with additional foot abnormalities.

[Sport after Total Knee and Hip Arthroplasty]. / Sport nach Knie- und Hüftendoprothetik.

The introduction of new materials and better implant coatings seems to provide the prerequisites for more intense physical activities after total joint arthroplasties of the lower extremity. Despite recent advances in implant design and materials, recommendations for sport after total joint arthroplasty have not been updated over the past 20 years. The introduction of modern uncemented fixation as well as highly cross-linked polyethylene into total hip arthroplasty allow for a more active life-style without an increased risk of loosening or complications. This publication reviews the literature and presents the current knowledge to provide guidelines for orthopaedic surgeons treating patients after total joint replacement surgery.

Do counteracting external frontal plane moments alter the intraarticular contact force distribution in the loaded human tibiofemoral joint?

BACKGROUND: There are strong indications that asymmetric medio-lateral load distribution in the knee joint is a risk factor for osteoarthritis. Externally applied frontal plane moments (adduction and abduction) might affect the distribution of knee joint compartment loading. However, this is not confirmed through intraarticular measurements in loaded human knee joints. The purpose of the study was to determine the force distribution and the movement of the centre of pressure in the loaded tibiofemoral joint as a function of varied externally applied counteracting frontal plane moments and in dependence of the knee flexion angle. METHODS: Adduction and abduction moments of 2.5 Nm and 5 Nm were applied to six cadaveric knees exhibiting varus, valgus and normal alignments. The joints were mounted in a knee joint loading simulator. During simulated muscle-driven extension-flexion cycles, intraarticular forces were determined using capacitive pressure sensors inserted into the medial and lateral knee joint compartments. Motion of femur and tibia were assessed by a motion analysis system. RESULTS: Externally applied frontal plane moments altered the intraarticular force distribution and caused shifts in the centre of pressure up to 4.3mm in all knee joints. Larger redistribution effects were found in higher knee flexion angles. The medial compartment load increased during the flexion in all investigated knee joints. CONCLUSIONS: The application of counteracting frontal plane moments for the conservative treatment of osteoarthritis can redistribute the forces and might slow down the progression of the disease. CLINICAL RELEVANCE: The findings of this study offer novel insights to guide the development and optimization of mechanical aids for the treatment of osteoarthritic knees.

Immunotherapy by gene transfer with plasmids encoding IL-12/IL-18 is superior to IL-23/IL-18 gene transfer in a rat osteosarcoma model.

BACKGROUND: Osteosarcomas are primary malignant tumors of bone or soft parts arising from bone-forming mesenchymal cells. Despite dramatic therapeutic advances, namely neo-adjuvant and adjuvant chemotherapy, progress is at a plateau. Cytokine-mediated gene therapy might represent a further advance in the therapy of the osteosarcoma. MATERIALS AND METHODS: We transfected UMR 108 osteosarcoma cells with different plasmids encoding IL-12, IL-23, proIL-18 and ICE (Interleukin-converting enzyme). IFN-gamma induction, which is known to induce antitumor effects mediated by the immune system, and cytotoxic effects of various cytokine combination were investigated. RESULTS: Our results show that local secretion of IL-12 by UMR 108 cells led to an induction of cytotoxic effects mediated by mononuclear cells, which were enhanced by additional administration of recombinant IL-18. In contrast to IL-18, IL-23 showed a moderate increase of IFN-gamma induction when transfected alone and could only slightly increase the IFN-gamma induction mediated by IL-12. IL-18 enhanced IFN-gamma induction when applied alone and was able to increase the IFN-gamma production that was induced by IL-12. CONCLUSION: IL-23 seems to be a less effective immuno-therapeutic for adjuvant treatment of osteosarcomas than IL-12 and IL-18, when taking only IFN-gamma induction into consideration.

Interleukin-12 and interleukin-18 induce indoleamine 2,3-dioxygenase (IDO) activity in human osteosarcoma cell lines independently from interferon-gamma.

PURPOSE: In this study we evaluated the ability of inducing activation of the enzyme indoleamine 2,3-dioxygenase (IDO) for the development of a new adjuvant therapy of osteosarcomas. The pathway that has described in the literature states that IDO activity is elevated by IFN-gamma. This mechanism is important because the increased IDO activation induces an intracellular degradation of the essential amino acid tryptophan and thereby activates apoptosis in human osteosarcoma cells. MATERIALS AND METHODS: Four different well-established human osteosarcoma cell lines (MNNG/HOS, KHOS-240, HOS and MG-63) were investigated in vitro. Several cytokines were tested for their ability to induce IDO activity. However special emphasis was placed to evaluate the synergistic effects of Interleukin-12 (IL-12) in combination with Interleukin-18 (IL-18). In the first series of experiments IDO induction was investigated by direct application of the cytokines IFN-gamma, TNF-alpha, IL-12 and IL-18 in different concentrations. Secondly, the increase of IDO expression from osteosarcoma cell lines was analysed in the presence of activated lymphocytes with or without cytokine application. RESULTS: Our results demonstrated that the combined application of IL-12 and IL-18 enhanced IDO activity in the human osteosarcoma cell lines HOS and MG-63, in the presence of activated lymphocytes. In the absence of activated lymphocytes, no significant enhancement could be detected. In all our experiments the increase in IDO expression was only partly inhibited by blocking INF-gamma. CONCLUSION: The presented study demonstrates that IL-12 and IL-18, or even more a combined application of both cytokines, induce IDO expression besides the known pathway via IFN-gamma. These mechanisms have been shown herein for the first time in human osteosacoma cell lines. Since IDO expression could still be shown after complete blocking of IFN-gamma, we conclude that at least a second pathway is responsible for inducing IDO activity. This is in contrast to the present knowledge about IDO activation.

rIL-18 triggered gene therapy based on a transduction with the IL-12 plasmid: a new option as immuno-therapy for osteosarcoma?

Gene therapy is a promising new method to treat tumors locally. Immuno-therapy for treatment of osteosarcomas is one option for hopefully improving the survival rate of patients with this tumor. Transduction of OS cells with the pCMV-IL-12neo plasmid induced a significant increase in IFN-gamma expression by mononuclear cells. This is known to induce antitumor effects mediated by the immune system. In combination with an administration of rIL-18, the IFN-gamma increase was multiplied in a dose-dependent manner. This study demonstrated that osteosarcoma cells can be targeted effectively in vitro by plasmids encoding the IL-12 gene. Considering the synergistic pathways it is reasonable to combine a local, gene transfer based on IL-12 with a rIL-18 administration to trigger the potentially promising immuno-effects for adjuvant treatment of osteosarcomas.

Isolated peripheral neurilemoma attached to the tendon of the flexor digitorum longus muscle.

Neurilemomas are benign tumours arising from peripheral nerves with a Schwann cell sheath. They are normally painless and slowly growing, rarely causing motor disturbances. Neurilemomas are most common in the cranial nerves, in the trunk, the upper and lower extremities, but may appear anywhere. Especially rare are neurilemomas of the lateral peroneal nerve in the region of the fibular head and in the foot. We present the first detailed report of a neurilemoma localized between the Achilles tendon and the flexor digitorum longus muscle with separation of the tumour from the tibial nerve.

Interleukin-12 and interleukin-18 change ICAM-I expression, and enhance natural killer cell mediated cytolysis of human osteosarcoma cells.

Cytokines play important roles in the expression of adhesion molecules and the function of anti-tumor effector cells in the immune system. In this study, the influence of interleukin-12 (IL-12) and IL-18 on the expression of ICAM-1 and natural killer (NK)-cell mediated lysis in a human osteosarcoma cell line (HOS) was evaluated. ICAM-I expression of HOS cells were analyzed by flow cytometry following treatment with IL-12, IL-18 or both, and in co-cultures with peripheral lymphocytes. NK-cell activation in response to IL-12 and IL-18 was investigated by selective flow cytometry using propidium iodide. ICAM-1 expression on HOS cells was significantly enhanced by IL-12, but only when co-cultured in cell-to-cell contact with peripheral lymphocytes. Antibodies to interferon-gamma abrogated this effect. If HOS cells and peripheral lymphocytes were separated in co-cultures, IL-18 could substitute for cell-to-cell contact, facilitating IL-12-mediated enhancement of ICAM-1. Addition of IL-18 also enhanced NK-mediated cytolysis of HOS cells. These findings demonstrate that IL-12 can enhance the expression of ICAM-1 in the presence of IFN-gamma and, with IL-18, enhances NK anti-tumor activity. Immunomodulation via cytokine therapy may lead to improved eradication of chemotherapy-resistant osteosarcomas.