Introduction: For the health-care system and for society in general, fractures of the femoral neck are epidemic among the elderly. With increased life expectancy, this type of pathology will continue increasing in the future. The study of possible biological causes of this phenomenon will provide better understanding of the pathology and help us prevent such fractures. Different genes involved in the synthesis of nitric oxide and interleukins are related to the occurrence of fractures of the femoral neck.

Materials and methods: We studied 111 patients with fractures of the femoral neck between 2002 and 2004 and a control group of 127 patients operated on for total hip or knee replacement in the same period. In both groups we looked at different genetic polymorphisms of IL-1 alpha, IL-1 beta, IL-1 RA, NOS2 and NOS3. We also measured the levels of IL-1 beta, IL-6 and TNF alpha in patient sera.

Results: We found a significant difference for certain genetic polymorphisms related to IL-1 beta and NOS3 and patients with fractures of the femoral neck.

Conclusions: There are different genes related to inflammatory reactants which are significantly related to the presence of fractures of the femoral neck.

Introduction: Aseptic osteolysis represents a significant challenge to the orthopaedic surgeon as it limits the long terms survivorship of prosthetic implants. Aim: To investigate whether the bisphosphonate aledronate alters the cytokine profile in the psuedomembrane excised from individuals undergoing revision hip arthroplasty surgery for aseptic failure. Methods: A prospective, double-blinded, randomised controlled trial was conducted with relevant ethical approval. 10 patients were randomly assigned to receive a placebo or alendronate 70mg for a 6 week period prior to revision surgery. All individuals had aseptic failure of primary cemented femoral stems and acetabular cups with UHDPE inserts. Infection was excluded in all individuals prior to surgery. Multiple tissue samples were subsequently excised at surgery and sent for histology and culture. If either was subsequently positive for infection the individual was excluded from the study. Tissue samples were preserved using liquid nitrogen and formalin. Frozen tissue was stored at −70. o. C pending Polymerase Chain Reaction analysis. Formalin preserved samples were paraffin sectioned for immunohistochemical analysis. PCR was carried out to assess expression of mRNA for Interleukins 1,6,17,18; TNF alpha, RANK-L, OPG and RANK. IHC was performed to confirm protein expression in the pseudomembrane excised from the femur and acetabulum. Multiple samples were used in each patient. Results: In the 5 individuals who received the placebo there was expression of mRNA and protein for Interleukins 1,6,17,18; TNF alpha; RANK-L; OPG and RANK in all cases. There was no statistically significant difference in the expression of any of the aforementioned cytokines/receptors in the group receiving alendronate. Discussion: A six seek course of oral alendronate 70mg had no effect upon osteoclastogenic cytokine expression when compared to the placebo group. This would suggest that alendronate may offer little benefit in reversing established particle induced osteolysis

A randomised controlled trial was conducted using a rabbit model of a complex contaminated extremity war wound. Compared to saline soaked gauze dressings Inadine (iodine) and Acticoat (nanocrystalline silver) had significantly lower levels of Staphylococcus aureus after 7 days while Activon Tulle (Manuka honey) had significantly higher levels. Molecular level analysis of the wound was conducted. Plasma cytokines of interest were assayed using ELISA and levels of expression of relevant tissue genes measured using PCR following RNA extraction. Appreciable levels of Interleukins 4 and 6 and Tumour Necrosis Factor-α were identified in plasma with significantly higher levels of IL-4 and TNFα detected in the Activon Tulle group. In tissue TNFα, Matrix metalloproteinase-3 and the ratio of Matrix metalloproteinase-9 to Tissue Inhibitor of Matrix metalloproteinase-1 were significantly higher in tissue injured limbs than the uninjured limbs with no significant differences between groups. Interpretation of these results is challenging. IL-4 has been associated with transition from pathological inflammation to repair and TNFα with impaired healing. However, Activon Tulle had significantly higher levels of S. aureus and we found no differences in observational, histology, haematology or tissue gene expression outcomes over 7 days which would correlate with these molecular biology results

Introduction: Metal-on-metal (MoM) articulations for THA are used successfully from CoCr-alloys. Low or high carbon hydride metals contain less or more than 0.2% carbon in the alloy. The systems show encouraging clinical results and lower rates of aseptic loosening in midterm results. Hypersensitivity reactions to high carbide MoM articulations were reported. The immune response is characterized by a perivascular T-/B-lymphocyte infiltration of the capsular tissue around the hip replacement. The present study examines if lymphocytic reactions are present in low carbide MoM THA and if distinct cytokines are released to joint fluids. Retrieval tissues from 28 patients were used. Joint fluids were aspirated at the time of surgery. Materials and Methods: Tissues were collected from 25 patients undergoing 26 aseptic revisions of MoM THA (CoCrMo, Sikomet. ®. , Plus Orthopaedics). The patients had following symptoms: Hip and femoral pain; recurrent dislocation and clicking noises. 8 patients had osteolysis, 12 patients showed a metallosis. The peripros-thetic tissues were examined by standard histology and immunohistochemistry. Joint fluids were frozen at the time of surgery. The control groups were patients with osteoarthritis of the hip (n=10), revisions from Al2O3-UHMWPE articulations (n=6), revisions of MoM with hypersensitivity reaction (n=18), and MoM without hypersensitivity reactions (n=8). The fluids were analyzed for various Interleukins, Il-1 receptor antagonist, G-CSF, GM-CSF, IFN gamma, MIP-1ß, and TNF-α. Results: 18 out of 26 cases showed diffuse and follicular lymphocyte infiltrations in the revision tissues. Perivas-cular T- and B-lymphocytes and few macrophages were also seen. In low and excessive metallosis no lymphocytes were observed. The tissue response in low carbide MoM is similar to high carbide MoM. Analysis of the cytokine profile in the joint fluids showed markers of osteoclast activation (Il-6 and −10) in all MoM articulations. TNF-α increase was increased in all loosening groups but was further increased in MoM. Il-5, IFN gamma, MIP-1ß, and GM-CSF were increased in all fluids from loosening cases but were further increased in MoM with lymphocyte activation. Discussion: Activation of lymphocytes in failed MoM THA’s is not necessarily related to high carbide MoM. Hypersensitivity also occurred in low carbide MoM THA. The cytokine profiles in the joint fluids showed distinct characteristics. Il-6 and Il-10, markers of osteo-clast activation, were elevated in all cases of bone loss and osteolysis. The increase in TNF-α may account for a regulation of the OPG/RANKL system TNF-a which can induce osteolysis. The elevated levels of Il-5, IFN gamma, MIP-1ß, and GM-CSF in MoM failures with hypersensitivity represent markers of chemotaxis and lymphocyte activation may account for index markers of hypersensitivity reaction