Metal hypersensitivity testing in patients undergoing joint replacement: a systematic review.

We report a systematic review and meta-analysis of the peer-reviewed literature focusing on metal sensitivity testing in patients undergoing total joint replacement (TJR). Our purpose was to assess the risk of developing metal hypersensitivity post-operatively and its relationship with outcome and to investigate the advantages of performing hypersensitivity testing. We undertook a comprehensive search of the citations quoted in PubMed and EMBASE: 22 articles (comprising 3634 patients) met the inclusion criteria. The frequency of positive tests increased after TJR, especially in patients with implant failure or a metal-on-metal coupling. The probability of developing a metal allergy was higher post-operatively (odds ratio (OR) 1.52 (95% confidence interval (CI) 1.06 to 2.31)), and the risk was further increased when failed implants were compared with stable TJRs (OR 2.76 (95% CI 1.14 to 6.70)). Hypersensitivity testing was not able to discriminate between stable and failed TJRs, as its predictive value was not statistically proven. However, it is generally thought that hypersensitivity testing should be performed in patients with a history of metal allergy and in failed TJRs, especially with metal-on-metal implants and when the cause of the loosening is doubtful.

Bone-targeted doxorubicin-loaded nanoparticles as a tool for the treatment of skeletal metastases.

Bone metastases contribute to morbidity in patients with common cancers, and conventional therapy provides only palliation and can induce systemic side effects. The development of nanostructured delivery systems that combine carriers with bone-targeting molecules can potentially overcome the drawbacks presented by conventional approaches. We have recently developed biodegradable, biocompatible nanoparticles (NP) made of a conjugate between poly (D,L-lactide-co-glycolic) acid and alendronate, suitable for systemic administration, and directly targeting the site of tumor-induced osteolysis. Here, we loaded NP with doxorubicin (DXR), and analyzed the in vitro and in vivo activity of the drug encapsulated in the carrier system. After confirming the intracellular uptake of DXR-loaded NP, we evaluated the anti-tumor effects in a panel of human cell lines, representative for primary or metastatic bone tumors, and in an orthotopic mouse model of breast cancer bone metastases. In vitro, both free DXR and DXR-loaded NP, (58-580 ng/mL) determined a significant dose-dependent growth inhibition of all cell lines. Similarly, both DXR-loaded NP and free DXR reduced the incidence of metastases in mice. Unloaded NP were ineffective, although both DXR-loaded and unloaded NP significantly reduced the osteoclast number at the tumor site (P = 0.014, P = 0.040, respectively), possibly as a consequence of alendronate activity. In summary, NP may act effectively as a delivery system of anticancer drugs to the bone, and deserve further evaluation for the treatment of bone tumors.

The potential role of metal ion release as a marker of loosening in patients with total knee replacement: a cohort study.

We investigated the role of ion release in the assessment of fixation of the implant after total knee replacement and hypothesised that ion monitoring could be a useful parameter in the diagnosis of prosthetic loosening. We enrolled 59 patients with unilateral procedures and measured their serum aluminium, titanium, chromium and cobalt ion levels, blinded to the clinical and radiological outcome which was considered to be the reference standard. The cut-off levels for detection of the ions were obtained by measuring the levels in 41 healthy blood donors who had no implants. Based on the clinical and radiological evaluation the patients were divided into two groups with either stable (n = 24) or loosened (n = 35) implants. A significant increase in the mean level of Cr ions was seen in the group with failed implants (p = 0.001). The diagnostic accuracy was 71% providing strong evidence of failure when the level of Cr ions exceeded the cut-off value. The possibility of distinguishing loosening from other causes of failure was demonstrated by the higher diagnostic accuracy of 83%, when considering only patients with failure attributable to loosening. Measurement of the serum level of Cr ions may be of value for detecting failure due to loosening when the diagnosis is in doubt. The other metal ions studies did not have any diagnostic value.

Knee arthrodesis with the Ilizarov external fixator as treatment for septic failure of knee arthroplasty.

BACKGROUND: The authors report the results of femoral-tibial fusion with an Ilizarov circular external fixator following septic loosening of knee prosthesis. MATERIALS AND METHODS: The series included 17 patients with a mean age of 62.9 years, treated from 1990 to 2007 with femoral-tibial fusion. The Cierny-Mader classification was used for clinical and anatomopathological evaluation; the Engh classification was used to assess the bone defect. Surgical treatment differed according to these criteria. RESULTS: Healing was achieved in 13 out of 17 patients at the first surgical attempt in a mean time of 9.3 months. Mean follow-up was 30 months. Of the four complications, two patients had an intolerance to the external fixator that led to its early removal, and the other two had a septic intraarticular nonunion. CONCLUSIONS: The Ilizarov circular external fixator is a very reliable fixation system due to its low cost, versatility, stability under load, and low risk of septic dissemination. Nevertheless, an appropriate patient selection and a good surgeon's experience are necessary.

Metal ion release from fracture fixation devices: a potential marker of implant failure.

Stainless steel is the alloy most frequently used for fracture fixation devices (FFD). We aimed to verify if the ion release evaluation could be a surrogate marker of performance and could allow an early detection of implant failure in patients with stainless steel FFD. We measured the nickel (Ni) and chromium (Cr) serum content in patients undergoing the retrieval of stainless steel plates (group I) or intramedullary nails (group II), because of consolidation or failure. Forty-five healthy donors were recruited as controls. Furthermore, the diagnostic performance of these values was evaluated: analysis power, sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic accuracy were calculated. A significant increase of ion values was demonstrated in patients with failed plates, compared with the values recorded in patients with well-fixed plates (p = 0.002 for Cr and p = 0.002 for Ni), and in healthy subjects (p = 0.0002 for Cr and p = 0.003 for Ni). No significant difference was found between stable implants and controls (p = 0.8 for Cr and p = 0.06 for Ni). A high specificity (0.92 for Cr and 1.00 for Ni), positive predictive value (0.87 for Cr and 1.00 for Ni), and positive likelihood ratio (9.10 for Cr) were calculated for ion testing in plates. The substantial metal content elevations in patients with plates and the positive likelihood ratio above 5 for chromium testing suggest that ion dosage may be a useful surrogate marker for the presence of malfunctioning of these devices, perhaps before the onset of clinical and radiographic changes.

Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells.

BACKGROUND: There is great interest in the use of bone substitutes to improve bone repair. We compared the osteogenic potential of lyophilized bone chips combined with platelet gel, or with platelet gel and bone marrow stromal cells, with that of lyophilized bone chips alone in the healing of a high tibial osteotomy. METHODS: A prospective, randomized, controlled study was performed, and a standardized clinical model was applied. Thirty-three patients undergoing high tibial osteotomy to treat genu varum were enrolled and assigned to three groups. During the osteotomy, lyophilized bone chips with platelet gel were implanted into eleven patients (Group A), lyophilized bone chips with platelet gel and bone marrow stromal cells were implanted in twelve patients (Group B), and lyophilized bone chips without gel were placed in ten patients as controls (Group C). Six weeks after surgery, computed tomography-guided biopsies of the grafted areas were performed and the specimens were analyzed by histomorphometry. Clinical and radiographic evaluation was performed at six weeks, twelve weeks, six months, and one year after surgery. RESULTS: Histomorphometry at six weeks showed significantly increased osteoblasts and osteoid areas in both Group A (p = 0.006 and p = 0.03, respectively) and Group B (p = 0.009 and p = 0.001) in comparison with controls, as well as increased bone apposition on the chips (p = 0.007 and p = 0.001, respectively), which was greater in Group B than in Group A (p < 0.05). Group B showed significantly higher revascularization than the controls (p = 0.004). Radiographs revealed a significantly higher rate of osseointegration in Groups A and B than in the controls at six weeks (p < 0.005 and p < 0.0001, respectively). At the final evaluation at one year, the osseointegration was still better in Groups A and B than in Group C; however, all patients had complete clinical and functional evidence of healing. CONCLUSIONS: Adding a platelet gel or a platelet gel combined with bone marrow stromal cells to lyophilized bone chips increases the osteogenetic potential of the lyophilized bone chips and may be a useful tool in the treatment of patients with massive bone loss.

Interferon-alpha inhibits in vitro osteoclast differentiation and renal cell carcinoma-induced angiogenesis.

Bone is a common site of osteolytic and richly vascularized metastases of renal cell carcinoma (RCC) and Interferon (IFN)-alpha based therapies have been considered for the treatment of patients affected by this disease. The effects of IFN-alpha on metastatic RCC patients have been related to its immunomodulatory, and cytotoxic activity on tumor cells, but there could be an effect also on tumor induced osteoclast differentiation and bone angiogenesis. When osteoclasts obtained from human peripheral blood mononuclear cells, cultured in the presence of receptor activator of nuclear factor-kappaB (RANKL) and macrophage-colony stimulating factor (M-CSF), were treated with IFN-alpha, the expression of bone tartrate resistant acid phosphatase (TRACP) type 5b was reduced, as well as calcium-phosphate resorption activity and expression of pro-osteoclatic transcription factor c-Fos. IFN-alpha modulation of angiogenesis was studied by analysis of proliferation, survival, and migration of a bone endothelial cell line (BBE), and by the analysis of pro-angiogenic factor expression in RCC cell lines. IFN-alpha inhibited bone endothelial cell proliferation and the expression of FGF-2, while the vascular endothelial growth (VEGF) did not show any significant variation. Moreover, IFN-alpha inhibited the migration induced by the RCC through the impairment of fibroblast growth factor-2 (FGF-2) secretion. These data demonstrate multiple activities of IFN-alpha on renal cancer-induced bone disease, in addition to its recognized role as a cytotoxic and immunomodulatory agent, because they indicate its ability to reduce bone resorption and to impair tumor-associated angiogenesis, and they also suggest the use of IFN-alpha to treat skeletal metastases of other carcinomas.

Human bone marrow stromal cells: In vitro expansion and differentiation for bone engineering.

Stromal cells from marrow hold a great promise for bone regeneration. Even if they are already being exploited in many clinical settings, the biological basis for the source and maintenance of their proliferation/differentiation potential after in vitro isolation and expansion needs further investigation. Most studies on osteogenic differentiation of marrow stromal cells (MSC) have been performed using bone marrow from the iliac crest. In this study, MSC were derived from spare femoral bone marrow obtained during hip replacement surgery from 20 adult donors. After in vitro isolation the cells were grown in osteogenic medium, and their proliferation and differentiation analysed during in vitro expansion. We found that MSC isolated from the femur of adult patients consistently maintain an osteogenic potential. Using biochemical signals, these cells turn to fully differentiated osteoblasts with a predictable set of molecular and phenotypic events of in vitro bone deposition. When seeded on polycaprolactone-based scaffold or surfaces, the proliferation and mineralization of femur-derived MSC were modulated by the surface chemistry/topography. Despite remarkable differences between individual colony-forming ability, alkaline phosphatase production, and mineralization ability, these cells are a potential source for bone engineering, either by direct autologous reimplantation or by ex vivo expansion and reimplantation combined to a proper scaffold.

In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination.

The repair of confined trabecular bone defects in rabbits treated by autologous bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone allografts (FDBA) alone and in combination (BMSC + PRP; FDBA + BMSC; FDBA + PRP; FDBA + PRP + BMSC) was compared. A critical size defect was created in the distal part of the femurs of 48 adult rabbits. Histology and histomorphometry were used in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing rate (%) was calculated by measuring the residual bone defect area. Architecture of the newly formed bone was compared with that of bone at the same distal femur area of healthy rabbits. The defect healing rate was higher in PRP + BMSC, FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC treatments, while lower values were achieved with PRP treatment at all experimental times. The highest bone-healing rate at 2 weeks was achieved with FDBA + PRP + BMSC treatment, which resulted significantly different from PRP (p < 0.05) and BMSC (p < 0.05) treatments. At 4 weeks, the bone-healing rate increased except for PRP treatment. Finally, the bone-healing rate of FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC was significantly higher than that of PRP at 12 weeks (p < 0.05). At 12 weeks, significant differences still existed between PRP, BMSC, and FDBA groups and normal bone (p < 0.05). These results showed that the combination of FDBA, BMSC and PRP permitted an acceleration in bone healing and bone remodeling processes.

Differences in ion release after ceramic-on-ceramic and metal-on-metal total hip replacement. Medium-term follow-up.

Modern metal-on-metal bearings produce less wear debris and osteolysis, but have the potential adverse effect of release of ions. Improved ceramic-on-ceramic bearings have the lowest wear of all, but the corrosion process has not been analysed. Our aim was to measure the serum ion release (ng/ml) in 23 patients having stable hip prostheses with a ceramic-on-ceramic coupling (group A) and to compare it with the release in 42 patients with a metal-on-metal bearing (group B) in the medium term. Reference values were obtained from a population of 47 healthy subjects (group C). The concentrations of chromium, cobalt, aluminium and titanium were measured. There was a significant increase of cobalt, chromium and aluminium levels (p < 0.05) in group B compared with groups A and C. Group A did not differ significantly from the control group. Despite the apparent advantage of a metal-on-metal coupling, especially in younger patients with a long life expectancy, a major concern arises regarding the extent and duration of ion exposure. For this reason, the low corrosion level in a ceramic-on-ceramic coupling could be advantageous.

Evaluation of bone healing enhancement by lyophilized bone grafts supplemented with platelet gel: a standardized methodology in patients with tibial osteotomy for genu varus.

Orthopedic practice may be adversely affected by an inadequate bone repair that might compromise the success of surgery. In recent years, new approaches have been sought to improve bone healing by accelerating the rate of new bone formation and the maturation of the matrix. There is currently great interest in procedures involving the use of platelet gel (PG) to improve tissue healing, with satisfactory results both in vitro and in maxillofacial surgery. Otherwise, to our knowledge, only a preliminary clinical study was undertaken in the orthopedic field [Kitoh et al., Bone 2004;35:892-898] and the efficacy of PG is still controversial. Our paper focuses on the effect on bone regeneration by adding PG to lyophilized bone chips used for orthopedic applications. The clinical model and the laboratory methodology were standardized. As a clinical model, we employed the first series of patients of a randomized case-control study undergoing high tibial osteotomy (HTO) for genu varus. Ten subjects were enrolled: in 5 patients lyophilized bone chips supplemented with PG were inserted during tibial osteotomy (group A); 5 patients were used as a control (group B) and lyophilized bone chips without gel were applied. Forty-five days after surgery, computed tomography scan guided biopsies of grafted areas were obtained and the bone maturation was evaluated by a standardized methodology: the osteogenic and angiogenic processes were semi-quantitatively characterized by using histomorphometry, and the mineral component of the lyophilized and host bone was analyzed by using X-ray diffraction technique with sample microfocusing and microradiography. Lyophilized bone with PG seems to accelerate the healing process, as shown by new vessel formation and deposition of newly formed bone, with no evidence of inflammatory cell infiltrate, when compared with lyophilized bone without gel. On the contrary, lyophilized bone undergo a resorption process, and a fibrous tissue often fills the spaces between chips. A histiocytic/giant-cell reaction is sometimes present. Otherwise, no differences have been found concerning microstructure. Our findings show the reliability of the methodology used to monitor early bone repair. The completion of the study and the evaluation of the ultimate clinical outcome are necessary in order to verify PG in vivo effects in orthopedic surgery.

Poly-epsilon-caprolactone/hydroxyapatite composites for bone regeneration: in vitro characterization and human osteoblast response.

Polycaprolactone (PCL), a semicrystalline linear resorbable aliphatic polyester, is a good candidate as a scaffold for bone tissue engineering, due to its biocompatibility and biodegradability. However, the poor mechanical properties of PCL impair its use as scaffold for hard tissue regeneration, unless mechanical reinforcement is provided. To enhance mechanical properties and promote osteoconductivity, hydroxyapatite (HA) particles were added to the PCL matrix: three PCL-based composites with different volume ratio of HA (13%, 20%, and 32%) were studied. Mechanical properties and structure were analysed, along with biocompatibility and osteoconductivity. The addition of HA particles (in particular in the range of 20% and 32%) led to a significant improvement in mechanical performance (e.g., elastic modulus) of scaffold. Saos-2 cells and osteoblasts from human trabecular bone (hOB) retrieved during total hip replacement surgery were seeded onto 3D PCL samples for 1-4 weeks. Following the assessment of cell viability, proliferation, morphology, and ALP release, HA-loaded PCL was found to improve osteoconduction compared to the PCL alone. The results indicated that PCL represents a potential candidate as an efficient substrate for bone substitution through an accurate balance between structural/ mechanical properties of polymer and biological activities.

Effects of activated platelet concentrates on human primary cultures of fibroblasts and osteoblasts.

BACKGROUND: Platelet alpha granules contain growth factors released into the surrounding environment during activation. This property has been used in clinical medicine to accelerate the repair process by activating in vitro autologous platelets with thrombin and has also been proposed to promote the proliferation of bone cells. The aim of this research was to assess the effect of platelet concentrates activated with thrombin on human gingival fibroblasts and human osteoblasts from trabecular bone. METHODS: Platelet concentrates, activated with bovine thrombin, were added to the cells in serum-free medium. The cultures were assessed for proliferation by vital stain and cell count after 72-hour incubation. Alkaline phosphatase activity was tested after 72-hour incubation on the osteoblast lysates by a colorimetric assay. After 21 days the formation of mineral nodules was tested in the osteoblast cultures by alizarin red staining. The effects of the activated platelet concentrates (APC) were compared with the serum-free medium (SF), or with platelet-poor plasma added medium (PPP). RESULTS: The fibroblast growth in the presence of APC was higher, though not significantly, than SF. APC resulted in a nonsignificant decrease in proliferation and alkaline phosphatase expression in osteoblasts, compared both to serum free medium, and PPP. Mineralization was only modestly increased after incubation with APC in comparison with serum-free medium. CONCLUSIONS: There were no statistical differences in fibroblast proliferation, or in osteoblast growth and functions between serum-free conditions and the platelet gel treatment. Therefore, neither fibroblast proliferation nor osteoblast growth and functions were affected by the activated platelet concentrates in vitro.

Systemic cross-linked N-terminal telopeptide and procollagen I C-terminal extension peptide as markers of bone turnover after total hip arthroplasty.

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV). The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.

Bone with cement and antibiotic: antibiotic release in vitro.

It was the purpose of the study to evaluate morcellized bone with cement and antibiotic release mixed with vancomycin and methylmethacrylate cement (PMMA). The aim of the study is part of a wider one aimed at verifying the possibility of using this composite for the treatment of chronic septic pathologies of the bone. Five cylinders 1 cm in height by 1 cm in diameter, formed by morcellized bone with cement and vancomycin were immersed in plasma and 5 in physiological solution. Three cylinders equal in size but formed by cement and antibiotic alone were immersed in plasma and 3 in physiological solution. All of the cylinders remained in immersion for 28 days at a temperature of 37 degrees C. The immersion fluids were changed every day during the first week and on days 14, 21 and 28. The quantity of vancomycin released was dosed in each specimen. The greatest and most constant release of antibiotic took place in the cylinders of morcellized bone, cement and antibiotic immersed in plasma.

Evaluation of osteoblast-like cell response to Proroot MTA (mineral trioxide aggregate) cement.

Some endodontic sealers have been shown to cause local and systemic effects, mainly due to microleakage of chemicals from the sealer. To avoid the risk of toxic effects in vivo, the biological compatibility of filling materials has to be assessed. In vitro compatibility of Proroot MTA cement in comparison with two different fillers used in clinical practice, was examined by testing the adherence, viability, proliferation and secretion of collagen of osteoblast-like cells. In our experimental system, Saos-2 cells challenged with Proroot MTA for 24 and 72 h showed a better behaviour than the cells exposed to the other compounds under assay. We found that the cells attached to the rough surface of Proroot MTA cement and spread onto the rough surface. Moreover, the cells on Proroot MTA were viable, grew, and released some collagen even at 72 h, while cell metabolism and growth was dramatically reduced onto sEBA and amalgam surfaces. A parallel behaviour was found after the cells were challenged with extracts of the different fillers. In conclusion, according to our in vitro study, Proroot MTA showed a good interaction with bone-forming cells: such behaviour may partially account for its satisfying clinical performance.

Diagnosis of infection after total hip replacement.

Subclinical infection in patients with pain following total hip replacement (THR) is an underestimated condition that needs consideration because it mimics aseptic loosening, contributes to periprosthetic osteolysis, and necessitates proper treatment. We aimed to define the reliability of diagnostic parameters that are routinely used before revision surgery for the assessment of infection. A continuous series of 26 subjects who underwent THR revision surgery was considered, including 21 cases diagnosed as aseptic loosening (group A) and 5 hip revisions with a clinical diagnosis for infection (group B). Seven subjects at the time of the primary arthroplasty were used as negative controls (group C). Technetium-99m labeled hydroxymethylene diphosphonate [(99m)Tc-HDP]- and technetium-99m hexamethylpropyleneamine oxide [(99m)Tc-HMPAO)]-labeled granulocyte scintigraphy, histology of peri-implant tissues, laboratory tests for inflammation, and microbiology were performed. Scintigraphy was positive for loosening [positive (99m)Tc-HDP scan] but negative for infection [negative (99m)Tc-HMPAO-labeled granulocyte scan] in all group A patients, whereas in 11 cases (52%) a positive culture was unexpectedly obtained. Histology showed conflicting results: Polymorphonuclear cells (PMNs) were found only in 5 of 11 culture-positive patients, whereas in 2 cases the presence of PMNs did not correspond to a positive culture. In group B patients, both isotope scans and microbiology were found to be positive. All control subjects (group C) had negative cultures. In our opinion, smoldering infection could be present in a significant proportion of cases of failed hip implants currently diagnosed as "nonseptic." The inflammatory response to wear debris and the presence of superimposed, slowly growing bacteria could act synergically, both contributing to the pathogenesis of periprosthetic osteolysis.

The influence of alumina and ultra-high molecular weight polyethylene particles on osteoblast-osteoclast cooperation.

Particle-induced macrophage activation, mainly by UHMWPE wear, has been recognized as the biological mechanism leading to periprosthetic bone resorption, which is responsible for the loosening of the total hip replacements (THR). Ceramic-on-ceramic implants have been advocated as a means of reducing wear products. Many studies investigated the effect of alumina (Al(2)O(3)) particles on monocytes/macrophages, but only limited information are available on their participation to bone turnover. An in vitro model was performed to investigate how Al(2)O(3) and UHMWPE particles may influence the osteoblast-osteoclast interaction: human osteoblasts (HOB) were obtained from trabecular bone, while osteoclasts were derived from peripheral blood mononuclear cells (PBMC) of healthy donors. The amount of IL6, TNF alpha, GM-CSF, and other factors acting on the bone turnover, i.e. the 'receptor activator of NF kappa B' ligand (RANKL) and osteoprotegerin (OPG), was detected in culture medium of particle-challenged HOB (HOB-CM). The Al(2)O(3) and UHMWPE particles did not affect either cell viability or TNF and GM-CSF release, while the increase in IL6 release seemed to be dependent on the particle concentration. UHMWPE increased the release of RANKL from HOB, while OPG and OPG-to-RANKL ratio were significantly inhibited. The ability of HOB-CM to promote osteoclastogenesis was tested via osteoblast/monocyte cooperation: after seven days of culture UHMWPE HOB-CM induced a large amount of multinucleated TRAP-positive giant cells, as well as significantly reduced the amount of IL6, GM-CSF and RANKL in the supernatant. With regard to the inductive effect on the osteoclastogenesis, our results show that the Al(2)O(3) wear debris are less active.

MRI in diagnosis of osteoid osteoma of the proximal femur: a potentially deviating aspect. Description of a clinical case.

Osteoid osteoma constitutes 10-12% of all benign neoplasms of the bone. The tumor more frequently involves the male sex (male to female ratio 2.1:1) and it may be observed in all age groups, with evident predilection for the second decade of life. All of the skeletal segments may be affected, but the most frequent site is the long bones, in the diaphyseal, metaphyseal and more rarely epiphyseal regions. The lesion is characterized by an osteolytic area, the nidus, which is at times partially calcified, surrounded by an osteosclerotic zone that is more or less accentuated. Clinical suspicion and traditional radiography are essential in diagnostic orientation; usually, further imaging methods are also recommended, such as bone scan with Tc99, CT scan and MRI. This last method allows for easy localization of the lesion, although with a sensitivity that is less than that of the CT scan. Nonetheless, the finding, if not supported by clinical suspicion, may be dangerously deviating and it may orient diagnosis towards a more aggressive disease.

Deep peroneal nerve paresis in a runner caused by ganglion at capitulum peronei. Case report and review of the literature.

Although lateral popliteal sciatic nerve damage is not one of the commonest diseases in the general population, it is quite frequent among athletes. Several physiopathologic mechanisms have been thought to bring about this damage in athletes. Soft tissue ganglions with neurological involvement of the lateral popliteal sciatic nerve or its terminal rami are in differential diagnosis with several lesions of this area, as direct or indirect trauma, subcutaneous rupture of anterior tibialis muscle and long peroneal muscle, disc hernia, intraspinal tumor, anterior tarsal tunnel syndrome, cysts, neurofibroma, baker's cyst, vascular claudication, stenosing or inflammatory pathology of 2(nd) motoneuron, antimicrobial agents for urinary tract infection (nitrofurnantoin). The authors report the case of a 34-year-old amateur athlete with a recent paralysis of the hallux extensor, paresis of the toe extensor and hyposthenia of the tibialis anterior. The patient had been suffering from episodes of lumbalgia for a long time. He was sent to us because neurological damage due to disc herniation was suspected. Electromyography, sonography, and CT showed peripheral compression of the deep peroneal nerve caused by a mucous cyst at the capitulum peronei, a ''rare'' condition. The patient underwent surgery to excise the cyst, which led to the rapid resolution of the nerve deficit shown by clinical and electromyographical tests. A meticulous anamnesis and accurate objective examination, followed by specific tests (radiographs, sonography, and possibly CT scan) generally enable a correct diagnosis to be made. If diagnosis and therapy are carried out correctly, and without delay, symptoms quickly resolve and the nerve deficit progressively regresses.