Aim

The aim of this prospective comparative study was to evaluate the serum levels of different cytokines in patients underwent total knee replacement (TKR) and received allogeneic blood transfusion, post-operative auto-transfusion or not transfused.

Several observational and experimental studies have investigated the potential anabolic effects of statins on undisturbed bone but only a few recent studies have examined the effect of statins on skeletal repair. The goal of the study is to investigate any potential early anabolic effect of the systemic administration of simvastatin in low doses (based on earlier safety and efficacy studies on undisturbed bone) on fracture healing.

Fifty-four skeletally mature male New Zealand White rabbits were used for the study. The rabbits were assigned to one of three experimental groups: a control group, and two groups that were orally administrated a diet with 10 and 30 mg/kg/day of simvastatin, respectively. A complete biochemical blood count was performed to exclude drug-induced complications. Half of the animals of each group were sacrificed at 15 days and the other half at 30 days after surgery at which time intervals healing quality was assessed. The bones were subjected to biomechanical testing, histomorphometric analysis and peripheral Quantitative Computed Tomography.

In animals received simvastatin of 30 mg/kg/day a significant reduction of BMD, stiffness, and energy absorbed to failure were observed. At 15 days, the amount of cartilaginous callus formation was reduced, and the void space was significantly increased, in the animals of both groups that received simvastatin when compared to the control group (p< .05).

Our results suggest that simvastatin doses of 30mg/ kg/day may have a negative anabolic effect on callus formation in rabbits, whereas doses of 10 mg/kg/day seem not to produce a significant positive or a negative effect, especially at the early stages of fracture remodeling.

We investigated the effect of Platelet Rich Plasma (PRP) in tendon healing. The aim was to assess the effect of an application of PRP on angiogenesis and immunohistochemical expression of TGF-b1 and IGF-I during tendon healing. We used a patellar tendon defect model after resecting its central portion. 48 skeletally mature New Zealand White rabbits were divided into the respective group and each group they were randomised into controls and PRP treated cases. The rabbits were sacrificed at weekly intevals and histological and immunohistological assessments were performed. The results showed a faster healing rate, increased vascularity, and higher expression of the growth factors in the PRP group. We conclude that the mixture of growth factors present in PRP gel improved the rate and quality of tendon healing.

Objective: Primary reconstruction of soft tissues in acute complex lower limb injuries is often mandatory in order to protect exposed bones, nerves, tendons and/or vessels, however it may be precluded by general clinical and/or local wound conditions. Vacuum assisted closure (VAC^®) has been introduced in the management of complex wounds for its ability to remove third space fluids, improve oxygen delivery to the wound bed, while it promotes angiogenesis and granulation. This retrospective study evaluates the use of VAC^® in lower limb trauma patients unsuitable for immediate reconstruction.

Patients and Methods: Fourty-two patients, 24 males and 18 females, with 49 complex lower limb traumas were treated with VAC^® therapy for a mean of 28 days (range 15–42 days). Mean age of patients was 47 years (range 21–82). All patients included were characterized by poor general condition or adverse local wound factors. VAC^® was applied 24–48 hours after bone fixation, vascular repair and surgical debridement of non viable tissues so as to minimize the risk of bleeding and ensure viability of soft tissues in the wound bed. Wound swab cultures were obtained before the application of VAC^® and before every change of sponge. The duration of therapy, wound flora, final reconstructive technique required, outcome and follow up period were recorded for each patient.

Results: Seventeen patients were over 65 years of age, 28 were Intensive Care Unit patients, 11 had heavily exuding wounds and in 9 the viability of soft tissues after initial debridement was questionable. Patients were followed up for 60 to 395 days. Two wounds (4%) healed spontaneously, 6 (12.2%) were managed with delayed direct suture, 31 (63.2%) were managed with skin grafts, 8 (16.3%) required local flaps. Two patients died during therapy due to concurrent conditions. In all but one patient, wound bacterial flora was progressively reduced during therapy. Scars were aesthetically acceptable, however, in 7 wounds hypertrophic scars were treated with triamcinolone injections combined with silicone sheeting.

Conclusion: VAC^® is a safe and effective method facilitating delayed soft tissue reconstruction in complex lower limb traumas in high risk patients. The development of healthy granulation tissue minimizes the need for major conventional reconstructive operations and therefore postoperative morbidity.

Objectives: The aim of this study was to explore the relationship between stress fractures, bone density and factors related to bone metabolism in a comparative group matched study including male military personnel beyond basic training.

Materials and Methods: Thirty two patients with stress fractures were matched with 32 uninjured-healthy volunteers (controls), by gender, age, height, body weight and level of physical performance. A questionnaire concerning the calcium intake, alcohol consumption and smoking was completed, the values of several biochemical markers related to bone metabolism were measured from blood samples, and calcaneal quantitative ultrasound was measured by heel ultrasound for each one of the 64 patients and healthy volunteers.

Results: Statistically significant lower levels of serum Osteocalcin (p=0.012) and higher levels of Albumin (p=0.006) were found among patients compared to controls. The levels of serum Total Protein, Ca, intact Parathormone and 25-hydroxy Vitamin D were lower among patients compared to controls, but none of these differences was statistically significant (all p> 0.10). Moreover, mean values of T-scores and Z-scores were statistically significantly lower in patients than in controls (p=0.018 for T-scores; p=0.016 for Z-scores).

Conclusions: Decreased bone turnover and low calcaneal bone density may increase the incidence of lower extremity stress fractures among men military personnel.

Introduction: Approximately 15% of fractures account for delayed or impaired healing. The popularity of new

Methods: that enhance fracture healing along with conventional ones is growing. The purpose of this study was to determine the effects, the safety and the efficacy of systemic simvastatin administration to bone healing.

Materials and Methods: Unilateral mid-ulnar osteotomies (approximately 2.0 mm wide) were performed to 56 skeletally mature male rabbits. The limbs were assigned to one of three groups: those treated with 30 mg/kg/day of simvastatin per os, those administered with 10 mg/kg/day of simvastatin orally and the control group. The rabbits were killed at two or four weeks postoperatively after taking blood samples for biochemical analysis to detect drug-induced side effects. After the rabbits were killed, the limbs were scanned with peripheral quantitative computed tomography to assess the area and mineral content of the mineralized callus. The bones were subjected to mechanical bending testing and histomorphometry.

Results: At 2 weeks the total density for the mineralized callus was on average 531.7±32.7 for the control group, 466.05±10.6 for the first group (p< .01) and at 4 weeks the total density was 617.5±12.42 for the control group, 551.26±27.61 for the first group, and 553.72±20.66 for the second group respectively (p< .001). Biomechanical properties were similar to all groups at 2 and 4 weeks. The% cartilage portion area was 17.28±2.61 for the control group, 11.89±1.84 for the first group (p< .001) and 14.06±2.17 for the second group (p< .05).

Discussion: The data show that daily systemic administration of simvastatin in 30 mg/kg/day or 10 mg/kg/day do not seem to produce a clear anabolic effect in fracture healing through the remodeling phase.

Conclusion: The use of simvastatin to promote fracture healing is still under study. The limitations from its use are the side effects from its systematic administration over 30 mg/kg/day. Most likely, alternative ways of administration should be considered for future studies.

Joint replacement implants, especially in their modular forms, are subjected to wear and corrosion at various sites in their articulation, such as the bearing surfaces, the undersurface of the insert, the femoral head-neck junction and the implant or polymethylmethacrylate-bone interface. Movement of the bearing surfaces is not the only cause, as faulty implant positioning can initiate wear through impingement between two parts of the articulation.

These wear products of polyethelene or metal, in particulate form, are influential to the ultimate fate of the prostheses through the initiation of local and systemic immune reactions.

These debris are phagocytised by macrophages and phagocytised proteins are partly degraded in intracellular vesicles, where they become associated with the major histocompatability complex molecule HLA-DR. This molecule when transported to the cell membrane, interacts with CD4+ lymphocytes to activate an immune response and initiate the production of interleukin1b, interleukin 6 and tumor necrosing factor a. These cytokines mediate the inflammatory response and activate osteoclasts causing periprosthetic osteolysis.

Polyethelene and metal wear particles, in addition to their local effects, can be disseminated beyond the periprosthetic tissues and reach distant organs and regional lymphnodes. The concentrations of certain elements of metallic implants, such as iron, cobalt, chromium or titanium have been detected in lymphnodes, the liver and the spleen in levels a lot higher than normal, especially in patients with loose prostheses and, less so, in patients with stable prostheses.

The reported values of metal ions in published series vary. Thus certain investigators (Brodner et al) have reported continuous systemic cobalt release during a five year follow-up period and in levels slightly above detection values, while others (Clarke et al, Lohtka et al) have reported consistently high levels of cobalt and chromium ions in metal on metal articulations. The diameter of the femoral head appears to be a significant factor. In surface hip replacements with large diameter heads the amount of detected metal ions was significantly higher compared with total hip replacements with use of 28mm diameter femoral heads. In that type of replacement the levels of cobalt was 50 times higher than normal and of chromium 100 times higher.

Polyethelene particles, similarily have been detected in paraaortic lymphnodes in percentages similar to metal ions. However the detection of PE particles in the liver or the spleen was less, compared to metal ions, possibly due to the difficulty of modern methods to detect PE particles of submicrometre size. The relevance of the dissemination of metal ions and of PE wear debris in organs distal to the operated joint need to be carefully evaluated since certain of these elements are known carcinogens. Two studies have reported slight increase of haemopoeitic cancers in patients with cobalt alloy implants and in patients with metal on metal devices, while others have documented the development of malignant tumours in the vicinity of total hip replacements.

Since prostheses with metal on metal bearing surfaces are used more and more frequently in younger patients, these patients require careful monitoring for longer periods.

In thirty-one rat tibiae, plugs of plain acrylic cement were inoculated with Staphylococcus aureus; these all remained contaminated at the end of two weeks when the animals were killed. Inoculation with known strains of Pseudomonas, Proteus and Gp. G Streptococcus resulted in 70 to 93 per cent persisting contamination. Gentamicin, to which the organisms were fully sensitive, was efficacious in controlling the infection (90 per cent plugs proving sterile after two weeks). Fucidin was less successful against Staphylococcus aureus although effective in vitro. Intravenous inoculation with a suspension of Staphylococcus aureus succeeded in contaminanting 70 per cent of sixty plain cement plugs when injected into the tail vein half an hour after closure of the leg wounds. Only 11 per cent of sixty-four plugs were so contaminanted when the injection was delayed for two weeks. This animal model is submitted as a possible future means of testing different antibiotic-cement combinations against infection.

Laboratory experiments and clinical investigations have confirmed the various claims made originally by Buchholz and Engelbrecht (1970) that antibiotic-loaded acrylic cement releases the antibiotic into the surroundings in useful concentrations. Palacos R cement released higher concentrations than CMW, Simplex and Sulfix brands of cement and over longer periods. Concentrations of gentamycin and fucidin were sufficient to penetrate dead cortical bone. These conclusions need to be assessed with animal studies, mechanical testing and clinical results before the ideal place of antibiotic-loaded acrylic cement is established.