Comparison between Operative and Non-Operative Treatment of the Medial Collateral Ligament: Histological and Ultrastructural Findings during Early Healing in the Epiligament Tissue in a Rat Knee Model.

The medial collateral ligament of the knee joint is one of the most commonly injured ligaments of the knee. Recent data have shown that the thin layer of connective tissue covering the ligament, known as the epiligament, is essential for its nutrition and normal function, as well as its healing after injury. The aim of the present study was to investigate and compare the changes in the epiligament of the medial collateral ligament which occurred during operative and non-operative treatment throughout the first month after injury. We used 27 male Wistar rats randomly allocated to three groups. In the 9 rats belonging to the first group, the medial collateral ligament was fully transected and left to heal spontaneously without suture. In the 9 rats belonging to the second group, the transected ends were marked with a 9-0 nylon monofilament suture. The 9 rats in the third group were used as normal controls. Three animals from each group were sacrificed on days 8, 16, and 30 after injury. Light microscopic analysis was performed on semi-thin sections stained with 1% methylene blue, azure II, and basic fuchsin. Transmission electron microscopy was used to study and compare the ultrastructural changes in the epiligament. The statistical analysis of the obtained data was performed using the Kruskal-Wallis H test and Mood's median test. The normal structure of the epiligament of the medial collateral ligament was presented by fibroblasts, fibrocytes, adipose cells, mast cells, collagen fibers, and neuro-vascular bundles. On days 8 and 16 postinjury, the epiligament appeared hypercellular and returned to its normal appearance on the thirtieth day postinjury. The electron microscopic study revealed the presence of different types of fibroblasts with the typical ultrastructural features of collagen-synthetizing cells. The comparative statistical analysis on the respective day showed that there was no statistically significant difference in the number of cells between spontaneously healing animals and animals recovering with suture application. These data further prove that spontaneous healing of the medial collateral ligament yields similar results to surgical treatment and may be used as a basis for the development of treatment regimens with improved patient outcome.

Comparison of stability and kinematics of the natural knee versus a PS TKA with a 'third condyle'.

PURPOSE: The goal of this study was to compare the kinematics of knees before and after total knee arthroplasty (TKA) that relies on an inter-condylar 'third condyle'. The hypothesis was that the 'third condyle' provides sufficient flexion stability and induces a close to normal femoral rollback, thus granting natural joint kinematics. METHODS: Intra-operative navigation data were collected from 29 consecutive cases that received a cemented TKA (HLS Noetos, Tornier SA, France) designed with an inter-condylar 'third condyle' that engages within the tibial insert beyond 35° flexion. Operations were guided by a non-image-based system (BLU-IGS, Orthokey Italia srl, Italy) that recorded relative femoral and tibial positions in native and implanted knees during: passive range of motion, anterior drawer test at 90° flexion, and varus-valgus stress tests at full extension and at 30° flexion. RESULTS: The total internal tibial rotation during flexion was similar for native (8.2 ± 4.2°) and implanted knees (8.0 ± 5.4°). The lateral femoral condyle was more posterior in implanted knees (1.2 ± 9.4 mm) than in native knees (9.5 ± 3.6 mm) throughout early flexion (p < 0.01), but this difference diminished beyond 100° flexion (n.s.). The implanted knees did not exhibit paradoxical external tibial rotation. Varus-valgus laxity in full extension was lower for implanted knees than for native knees (p = 0.0221), but at 30° flexion was almost identical for both native and implanted knees. Anteroposterior laxity was similar in implanted and native knees. CONCLUSIONS: The 'third condyle' TKA provides similar anteroposterior and mediolateral stability to the natural knee. This feature granted an adequate balance between laxity and constraint to reproduce natural joint kinematics, including smooth femoral rollback, without causing paradoxical external tibial rotation.

Antithrombotic prophylaxis in major orthopaedic surgery: an historical overview and update of current recommendations.

The risk of venous thromboembolism following major orthopaedic procedures, such as joint arthroplasty and hip fracture surgery, are well recognised and represent one of the major challenges in orthopaedic practice, having in mind the increasing number of arthroplasties of the hip and knee done worldwide per year and their successful outcome. This potentially fatal complication remains a challenge in orthopaedic practice. The percentage of patients in whom antithrombotic prophylaxis has not been administrated or has been inadequate may reach 50%. Until recently, anticoagulant prophylaxis with low molecular weight heparins (LMWHs) has been a "gold standard". LMWHs are indirect inhibitors of the clotting factors Xa and thrombin and are administered by daily subcutaneous injection. Their efficacy has been proven in numerous clinical trials and the rate of complications with their use is relatively low. However these compounds are associated with a failure rate and are inconvenient to administer, requiring subcutaneous injection, leading to inadequate compliance. For these reasons postoperative thrombembolism continues to occur in up to 10% of this patient population. Recently, novel oral anticoagulants have been introduced into practice for thromboprophylaxis after joint arthroplasy and hip fracture surgery. These drugs are direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban). These oral drugs have the same efficacy as the LMWHs with the same or slightly more clinically significant haemorrhage as their main side effect. Their ease of administration and favourable clinical profile makes them an important addition to the therapeutic armamentarium available for venous thromboprophylaxis. In this paper we review the aetiology and pathogenesis of venous thromboembolism and present the various alternatives for its prevention after major orthopaedic surgical procedures with emphasis on the new oral drugs.

Initial experience with Bulgarian Arthroplasty Register.

INTRODUCTION: National arthroplasty registries date back to 1975, when the Swedish Knee Arthroplasty Register was founded. This method of database collecting has since been employed for both patient follow-up and the creation of annual statistical reports. In Bulgaria, there is currently no state-approved software that offers these features.

Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion.

Mesenchymal stem cells (MSCs) are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process. The investigation of the influence of MSCs on the expression of FoxP3 and cytokine secretion by T helper cells was the aim of this study. T helper cells were isolated from PBMCs by magnetic separation and MSCs were isolated from human adipose tissue, and CD4⁺ T cells were cultured with conditional medium of MSCs. The methods which were used include flow cytometry, ELISA, and Human Proteome profiler kits. The results demonstrated that secretory factors in MSCs conditional medium lead to increased expression of FoxP3 and increased secretion of IL-10 by T helpers. The obtained results give us opportunity to discuss the interaction between two kinds of immunoregulatory cells: MSCs and FoxP3⁺ T helpers. We suppose that this interaction leads to increased number of immunosuppressive helpers which secrete IL-10. MSCs provide some of their immunosuppressive functions acting on T regulatory cells, and we believe that IL-6 secreted by MSCs is involved in this process.

Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population.

Background: Osteoporosis is a common chronic disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of the bone, which are associated with increased risk of fragility fractures. Currently the most popular tool is the fracture risk assessment model FRAX to calculate the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF). Objective: To investigate the prevalence of low BMD at axial sites and fracture risk in Bulgarian population. Methods: We retrospectively analyzed dual energy X-ray absorptiometry (DXA) scan results of 12 478 subjects. Scan results included BMD and T-score assessments of lumbar spine and femoral neck. FRAX major osteoprotic fracture (MOF) and FRAX hip fracture (HF) were assessed in subjects between 40 and 90 years using BMD values. Results: Of total 12478 subjects, 12119 were women and 359 were men. The mean age of the subjects was 61 years (yrs.) ± 10 yrs. The overall prevalence of low BMD at the lumbar spine was 6084/9336 subjects (65.2%). 3502/9336 subjects (37.5%) were considered as osteopenic and 2582/9336 subjects (27.7%) were considered as osteoporotic. The overall prevalence of low BMD at the femoral neck was 2036/3140 (64.8%). 1641/3140 subjects (52.3%) were classified as osteopenic and 395/3 140 subjects (12.6%) were classified as osteoporotic. The mean values of FRAX MOF and FRAX HF increased significantly with increasing the age interval. Conclusion: This study is the largest epidemiological research in Bulgaria up to date about the prevalence of low BMD at axial sites.

Histological and ultrastructural evaluation of the early healing of the lateral collateral ligament epiligament tissue in a rat knee model.

BACKGROUND: In this study, we evaluated the changes which occurred in the epiligament, an enveloping tissue of the ligament, during the ligament healing. We assessed the association of epiligament elements that could be involved in ligament healing. METHODS: Thirty-two 8-month old male Wistar rats were used in this study. In twenty-four of them the lateral collateral ligament of the knee joint was surgically transected and was allowed to heal spontaneously. The evaluation of the epiligament healing included light microscopy and transmission electron microscopy. RESULTS: At the eight, sixteenth and thirtieth day after injury, the animals were sacrificed and the ligaments were examined. Our results revealed that on the eight and sixteenth day post-injury the epiligament tissue is not completely regenerated. Till the thirtieth day after injury the epiligament is similar to normal, but not fully restored. CONCLUSION: Our study offered a more complete description of the epiligament healing process and defined its important role in ligament healing. Thus, we provided a base for new strategies in ligament treatment.

Advantages and disadvantages of 3D printing for pre-operative planning of revision hip surgery.

Total hip arthroplasty (THA) is one of the most successful and cost-effective interventions in medicine nowadays, providing reliable pain relief and functional improvement to those with osteoarthritis or inflammatory arthritis of the hip (P Kinov, B Antonov,'Possibilities for surgical treatment of acetabular osteolysis subsequent to revision arthroplasty of hip joint', Orthop Trauma. 52, 2015). Revision hip arthroplasty or severe reconstructive procedures in cases with significant anatomical defects require skilled surgical staff and accurate preoperative planning, including bone insufficiency, deficiency, discontinuity (anatomical assessment) as well as augmentation, cage or other requirements. (implant planning). Some authors recommend preoperative 3D model planning for precise anatomical assessment and preoperative training. This method has some limitations but could be successfully used in addition to conventional surgery.

Comparison of topical and intravenous administration of tranexamic acid for blood loss control during total joint replacement: Review of literature.

PURPOSE: Many randomised controlled trials and meta-analysis studies have presented the efficacy of tranexamic acid (TXA) without an increase of complications. However, questions still remain about the type of administration, optimal dose and secondary outcomes of TXA in total hip arthroplasty and total knee arthroplasty. The aim of this review is to summarise the existing information in literature concerning the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use. METHODS: A literature review containing 63 articles from the PubMed data starting from the first description of tranexamic acid until now was made in trying to present the existing information in a simple and effective way. RESULTS: TXA leads to statistically significant reduction of peri and postoperative bleeding and in that way decreases blood transfusion rates and the infection risk. Topical and intravenous (IV) use of TXA revealed similar results, with no increase of deep venous thrombosis. Therefore, topical TXA could be a reasonable alternative in patients with contraindications for IV application of TXA. CONCLUSIONS: Blood loss control with TXA, a synthetic analogue of the amino acid lysine, may be an excellent and safe alternative to allogeneic blood transfusion after total hip arthroplasty and total knee arthroplasty. Further studies are needed to establish the efficacy of combined IV and topical administration of TXA with regard to diminishing blood loss and reducing hospital stay. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This review briefly presents the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use with regard to diminishing blood loss and reducing hospital stay for better therapeutic strategies in orthopaedics.

Correlation between thigh pain and radiological findings with a proximally porous-coated stem.

Thigh pain has been consistently reported with cementless hip arthroplasty. The correlation between thigh pain and radiological findings and the clinical significance of thigh pain have not been studied in any detail. We carried out a retrospective study to analyse the performance of a proximally porous-coated cementless femoral component. Ninety-eight total hip arthroplasties were followed up clinically and radiologically for an average of 33 months (range: 12 to 64) after operation. The clinical results were good or excellent in 85 cases (87%). Thirteen patients (13%) reported thigh pain at latest follow-up. Subsidence of the stem was recorded in 10 cases, cortical thickening occurred in 14 hips (14%), and 17 hips (17%) presented proximal osteopenia. Proximally, radiolucent lines were observed in 11 cases. Thigh pain correlated with radiolucent lines, femoral thickening, fibrous fixation and stem migration. Bone remodelling was noted to continue even five years after implantation. Our observations demonstrated bone ingrowth in the majority of the cases and a low incidence of thigh pain. The correlation between radiological changes and thigh pain suggests implant micromotion and migration in some hips. Patients with thigh pain, changes in the proximal femur and progressive subsidence need further clinical and radiological follow-up.

Light and electron microscopic study of the medial collateral ligament epiligament tissue in human knees.

AIM: To examine the normal morphology of the epiligament tissue of the knee medial collateral ligament (MCL) in humans. METHODS: Several samples of the mid-substance of the MCL of the knee joint from 7 fresh human cadavers (3 females and 4 males) were taken. Examination of the epiligament tissue was conducted by light microscopy and photomicrography on semi-thin sections of formalin fixed paraffin-embedded blocks that were routinely stained with haematoxylin and eosin, Mallory stain and Van Gieson's stain. Electron microscopy of the epiligament tissue was performed on ultra-thin sections incubated in 1% osmium tetroxide and contrasted with 2.5% uranyl acetate, lead nitrate, and sodium citrate. RESULTS: The current light microscopic study demonstrated that the epiligament of the MCL consisted of fibroblasts, fibrocytes, adipocytes, neuro-vascular bundles and numerous multidirectional collagen fibers. In contrast, the ligament body was poorly vascularised, composed of hypo-cellular fascicles which were formed of longitudinal groups of collagen fibers. Moreover, most of the vessels of the epiligament-ligament complex were situated in the epiligament tissue. The electron microscopic study revealed fibroblasts with various shapes in the epiligament substance. All of them had the ultrastructural characteristics of active cells with large nuclei, well developed rough endoplasmic reticulum, multiple ribosomes, poorly developed Golgi apparatus, elliptical mitochondria and oval lysosomes. The electron microscopy also confirmed the presence of adipocytes, mast cells, myelinated and unmyelinated nerve fibers and chaotically oriented collagen fibers. CONCLUSION: Significant differences exist between the normal structure of the ligament and the epiligament whose morphology and function is to be studied further.

Role of free radicals in aseptic loosening of hip arthroplasty.

Fibrous pseudocapsule around hip implants is an invariable finding at revision operations and is believed to release inflammatory mediators that stimulate bone resorption. Reactive oxygen species have been proposed to be causative factors in various disorders with tissue fibrosis. We were interested in investigating whether aseptic loosening is connected with high oxidative stress, and in showing the underlying mechanism of periprosthetic fibrosis and its role in loosening. Levels of oxidative stress markers reduced (GSH) and oxidized (GSSG) gluthatione and malondialdehyde (MDA) were assayed in 28 loose hips and in 12 stable hips revised for high rate of wear and osteolysis. Collagen in the periprosthetic tissues was measured as hydroxyproline content. Osteolysis and polyethylene wear were graded. Increased oxidative stress measured by low GSH/GSSG ratio as well as by increased MDA level was established in patients compared to controls. Oxidative stress markers intercorrelated significantly. MDA and both GSH and GSSG levels correlated significantly with hydroxyproline level. Levels of GSSG and MDA were higher in hips with greater polyethylene wear. The results suggest that high oxidative stress may play a role in formation of a fibrous membrane observed at revision of loose hips. The fibrous pseudocapsule is probably related to high intraarticular pressure and expansion of the effective joint space. This study may elicit some aspects of the pathogenesis of aseptic hip loosening and aid in future investigations aiming at prevention of this complication.

Effect of risedronate on bone metabolism after total hip arthroplasty: a prospective randomised study.

Aseptic loosening due to bone remodeling and osteolysis is the main reason for revision hip arthroplasty. At present, there is no established prophylaxis for this complication. On the other hand, it has been demonstrated that bisphosphonates prevent bone loss around total hip arthroplasties (THA). The aim of this study was to assess the efficacy of oral bisphosphonate risedronate for the prevention of deleterious changes in bone metabolism after hip replacement. Twenty-four patients who underwent THA were randomised to two treatment arms: 35 mg risedronate once weekly for 6 months (12 patients) and no treatment for controls (12 patients). Markers of bone turnover bone specific alkaline phosphatase, serum osteocalcin and urinary deoxypiridinoline were evaluated at baseline, third and sixth postoperative month. Dual energy X-ray absorptiometry of the nonsurgical hip was performed preoperatively and at 6 months postoperatively. There were no significant differences in clinical or radiographic findings between the two groups at either 3 or 6 months. In the two groups, all biochemical marker responses at the third postoperative month were suppressed compared with baseline. Values of bone resorption marker urinary deoxypiridinoline increased significantly at six months in the control group. For the 10 risedronate patients with bone densitometry bone mineral density reached 1.01% increase at 6 months. Administration of oral risedronate led to a significant reduction in bone metabolism at 6 months after hip replacement. This therapeutic strategy may improve the results and longevity of total hip arthroplasty. The beneficial effect of risedronate should be confirmed in further studies including larger number of patients and longer follow-up. The action of risedronate could prevent aseptic loosening of hip arthroplasty by preserving periprosthetic bone stock.

Surgical treatment of periprosthetic femoral fractures following hip arthroplasty: our institutional experience.

PURPOSE: Periprosthetic fractures are one of the most serious complications after hip replacement. The aim of this retrospective study was to evaluate the clinical outcome of surgical treatment of periprosthetic femoral fractures following total hip arthroplasty using treatment algorithm of the Vancouver classification. MATERIALS AND METHODS: Fifty six periprosthetic femoral fractures operated on during the period December 2004-September 2013 were followed-up retrospectively. There were 40 women and 16 men with mean age at the time of surgery 64.7 years (41-88 years). The mean follow-up for the group was 5 years (range, 1-10 years). Periprosthetic fractures were classified according to the Vancouver classification. The clinical evaluation was performed with the Harris hip score, the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Short Form 8 (SF-8). Bone healing, implant survival, pain, function and complications were recorded. Bone healing and implant stability were evaluated clinically and on plain radiographs. RESULTS: Uneventful bone healing was achieved in 52 cases. In two fractures (one type B1, one type C) nonunion and plate failure occurred. Two cemented stems were revised for aseptic loosening 6.5 and 7 years after fracture fixation. Uncontrollable prosthesis infection and sepsis in a rheumatoid (immunocompromised) patient required disarticulation of the involved extremity. DISCUSSION AND CONCLUSIONS: Periprosthetic femoral fractures are difficult to treat and require complex treatment approach according to risk assessment, fracture type, implant stability, bone stock and medical status of the patient. Using a treatment protocol of the Vancouver classification we obtained satisfactory outcome.

Clinical utility of risedronate in postmenopausal osteoporosis: patient considerations with delayed-release formulation.

Bisphosphonates are the most widely prescribed treatment for postmenopausal osteoporosis, secondary osteoporosis, and male osteoporosis. Notwithstanding their high effectiveness and favorable safety profile, the adherence to bisphosphonate treatment remains low. Different treatment strategies aim to improve the clinical effectiveness of bisphosphonate therapy. This review paper assesses the clinical utility of oral intermittent risedronate in the treatment of postmenopausal osteoporosis. The new delayed-release risedronate formulation is a safer and easy to use alternative to other risedronate therapy. Oral risedronate, a potent nitrogen-containing bisphosphonate, has been extensively studied using daily regimens. A new intermittent (weekly) dosing regimen confirmed its clinical effectiveness in relation to vertebral and nonvertebral fracture prevention. The absence of significant differences in the incidence of adverse effects confirmed the favorable tolerability of the weekly dosage. In efforts to improve patient adherence to treatment, an innovative, delayed-release formulation of risedronate, which ensures adequate bioavailability of the active compound when taken with food, was introduced. The once-weekly delayed-release formulation of risedronate proved to be noninferior to the daily dosage of risedronate in terms of bone mineral density and markers of bone turnover. In addition, the incidence of new morphometric vertebral fractures was comparable in both treatment regimens. The new delayed-release formulation of risedronate showed a favorable safety profile. Delayed-release risedronate is a promising, new, effective, and convenient alternative to current bisphosphonate treatments. It appears to allow better patient adherence to antiresorptive treatment.

Revision total hip arthroplasty with cementing technique--five-year results.

AIM: To investigate the result of cemented revision hip arthroplasty. MATERIAL AND METHODS: Twenty-one revision hip arthroplasties for aseptic loosening with cementing technique during the period 1990-2002 were followed-up. There were 12 women and 9 men with mean age at the time of revision 61 years (33 to 76 years). The mean follow-up for the group was 5.2 years (range, 2 to 13 years). The clinical evaluation was performed with the Harris hip score. Implant survival, pain, function and complications were recorded. Plain radiographs were reviewed and the hips were graded for osteolysis and loosening. Wear of the polyethylene was measured. RESULTS: No component was exchanged. Three of the acetabular and three of the stem components in the hips with early cementing technique were loose. In two patients three surgeries were performed for trochanteric problems and persistent pain. Clinical result and bone defects preoperatively as well as wear and osteolysis correlated significantly. DISCUSSION: Stable fixation of the prosthesis is of paramount importance in revision surgery. In cases with severe bone defects stable interface is difficult to be achieved. This may change stress distribution and subsequently lead to loosening. CONCLUSION: Better preoperative planning and improvement in cementing technique may improve results. Other revision techniques may be considered in cases with severe bone deficiencies.