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.

Purpose: The aim of this study was to investigate the results of end-to-side neurorraphy of the common peroneal nerve (CPN) to the tibial nerve (TN) in rats, after administration of bFGF or NGF. Materials: Five (5) groups of adult male Wistar rats, each comprising 25 animals, were studied:

End-to-side neurorraphy (4 groups) Group A bFGF (20ng) Group B NGF (25ng) Group C (normal saline) Group X [bFGF (20ng) + NGF (25ng)]

All experimental procedures were performed under the supervision of a veterinarian and were prospectively approved by the Animal Experimental Ethics Committee.

Methods: In groups A, B and X, the CPN was sharply divided at a distance of 7mm distal to its origin from the rat sciatic nerve; the proximal CPN stump was then sutured into the thigh muscles, whereas the distal CPN stump was sutured terminolaterally to the ipsilateral TN. Sub sequently, a total volume of fifty microliters (50μl) of the corresponding solution of growth factor(s) was administered in each case beneath the epineurium, proximal to the CPN/TN coaptation site, with the aid of a microsyringe. The same surgical procedure was carried out in group C (positive control group), as well, but an equal volume (i.e. 50μl) of normal saline was administered instead. Finally, in each of the animals of the remaining group G, both the proximal and the distal stump of the CPN were carefully sutured into the neighbouring muscles; hence, the latter would constitute a negative control group, thanks to the resulting atrophy of the CPN – innervated musculature. All surgical procedures took place with the animals under dissociative anaesthesia and were performed under sterile conditions, using the operating microscope and applying microsurgical techniques. In each case, the right CPN was operated upon; the contralateral (left) CPN remained intact, thus serving as control. Euthanasia was achieved by means of intracardiac administration of high – dose sodium pentobarbital.

Results: The evaluation of the outcome four (4) months postoperatively was based on clinical examination, walking-track analysis, electromyographic and histomorphometric studies. Our data indicate that the administration of the growth factors under investigation has a favorable effect on the outcome of CPN repair; the administration of bFGF, in particular, seems to improve the results of terminolateral neurorraphy in the time span studied.

Conclusions: In rats, CPN repair via end-to-side neurorraphy to the TN can be enhanced by the administration of bFGF or NGF.

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.

AIM: Chronic osteomyelitis is a difficult to treat infection requiring prolonged antimicrobial therapy and involving systems of local antimicrobial delivery. Linezolid is a new antimicrobial agent with well documented in vitro activity against gram positive cocci when resistance to other antistaphylococcal agents is present. Few data are present regarding its embedding in local antimicrobial delivery systems and subsequent elution. The elution of linezolid by a polylactic acid (PLA) system was studied.

METHODS: Linezolid was dry-mixed with PLA at a ratio of 1:9, ie 50mg of linezolid were mixed with 450mg PLA. The mixture was diluted with 0,5mL of methanol and placed at the bottom of a cylindrical vial. Two replicas were created and one mL of Mueller-Hinton broth was added over the free solid surface of each mixture. Vials were transferred to a 37°C incubator and broth was replaced every 48h for 11 days. Concentration of linezolid was determined by an HPLC method using a Zorbax Eclipse XDB-C8 column and UV detection.

RESULTS: Mean linezolid concentration at days 1, 3, 5, 7, 9 and 11 was 2778.54 mg/L, 2456.22 mg/L, 668.63 mg/L, 324.86 mg/L, 390.10 mg/L, and 155.28 mg/L respectively.

CONCLUSION: Elution of linezolid by a PLA local delivery system remains very high throughout the period studied. The results are promising for the therapy of staphylococcal chronic osteomyelitis with the use of a PLA local antimicrobial delivery system employing linezolid.

Aims: The objective of our study is to elucidate the chondrogenic potential of free autologous periosteal grafts in treating articular cartilage defects, especially in complicated cases where apart from the cartilage defect there are coexisting lesions. Methods: 60 young rabbits were randomly divided in 5 groups. A cartilage defect 0.5 ⋄ 0.5 was created in both knees of each rabbit and covered with free autologous periosteal graft. In the right knee an additional ligamentous lesion was created. Results: All the knees were amputated at one, two and three months postoperatively. Apart from the histological examination, the cartilage specimens were tested biomechanically. An indentation test was used using a Shore A sclerometer and the data were evaluated and compared. In the test group the produced fibrocartilage or hyaline-like cartilage, was mechanically inferior (hardness 50–70 GPa) comparing to the control knees group (98 GPa). The results were statistically evaluated (using O’Driscoll’s histological grading scale and Wilcoxon rank sum test). Conclusions: Autologous periosteal transplantation can be used in daily practise, as it is a method relatively easy to perform with low cost and without any contra-indications. Nevertheless, in cases of unstable knees the method has poor results and ligamentous repair is recommended first.

Aims: The effectiveness of the local treatment of experimental osteomyelitis caused by MRSA (Methicillin Resistant Staph. aureus) performed with the implantation of acrylic bone cement (PMMA) mixture plus 4% grepaßoxacin into the femur of rabbits. Methods: 36 rabbits with chronic MRSA osteomyelitis of the right femur (Norden Model) were treated with a new local grepaßoxacin delivery system prepared by a mixture of PMMA plus 4% grepaßoxacin. Osteomyelitis was introduced by inoculating of the MRSA and the placement of a needle serving as a foreign body. The follow-up of the infection was performed by clinical, microbiological and x-rays þndings. On the 3rd week all animals were reoperated and the needle was removed followed by implantation of the mixture. One control and þve treated animals were sacriþced each week thereafter until the 6th week. Results: Osteomyelitis was induced in all rabbits. The in vitro grepaßoxacin levels were high for 6 weeks at least. Concerning the histological þndings serious tissue reactions were not observed. The lesions and the bone structure are progressively rehabilated after the implantation. The biomechanical study didnñt inßuence the mechanical properties of bone cement due to grepaßoxacin. Conclusions: The above mixture could be an approved supplementary method for the treatment of bone infections. In the chronic osteomyelitis itñs possible to replace the gentamycin PMMA beads. Furthermore could be use as a spacer in loosen arthroplasties due infection in combination with antibiotic administration.

Aims: The effectiveness of the local treatment of experimental osteomyelitis by MRSA with a mixture of calcium phosphate bone cement and 3% teicoplanin into the femur of rabbits.

Methods: Thirty-six male rabbits with chronic (3 weeks) MRSA (Methicillin Resistant Staph. aureus) osteomyelitis of the right femur (Model of Norden CW) were treated with a new local Teicoplanin delivery system prepared by a mixture of calcium phosphate cement plus 3% teicoplanin. Osteomyelitis was introduced by inoculating 107 cfu/ml of the MRSA strain in a 2mm hole of the bone medula, placement of a needle serving as a foreign body and subsequent closure with a sterile bone wax. The follow-up of the infection was performed by clinical, microbiological, x-rays and histological findings. On the third week all animals were reoperated and the needle was removed followed by implantation of the above mixture. One control and five treated animals were sacrificed each week thereafter until the sixth week.

Results: Cultures of the treated animals were positive during the first week but turned negative after the second week, while throughout the same period cultures from the controls remain positive. Clinical and histologic studies were in accordance.

Conclusions: The above mixture could be approved as a supplementary method in the treatment of bone infections. It can be used by replacing the gentamycin polymethylmethacrylate beads whose use demands reoperation to be removed. Finally it offers the possibility to contribute to the filling of the bone gaps as it can be replaced by host bone.