Post-operatively we measured the mean MFT angle in groups A, B and C. In group A, the mean MFT angle was −0.38° varus (−4° to 2°), group B was −0.41° varus(−5° to 2°), and group C was −0.02° varus(−3° to 5°). P=0.7 using the Kruskal-Wallis test. These results show that the post-operative kinematics are similar between the three different populations.
Pre- and post-operatively, the surgeon applied a varus and valgus stress at maximum extension, recording the mechanical femorotibial (MFT) angle. There were no patellar resurfacings. We compared the kinematics of each varus knee. Based upon the kinematics and the surgeon’s experience the following medial releases were performed as usual and divided into three categories:
No release (limited medial approach). Moderate release (postero-medial release including the semimembranosis). Proximal (extensive) release.
With the following medial releases, these kinematics were found:
No release – MFT angle not less than −12° with varus stress, greater than 2° with valgus stress, and/or if extension deficit was not greater than 5°. Moderate release – MFT angle less than −12° with varus stress, between −5° and 2° with valgus stress, and/or extension deficit not greater than 5°. Proximal release – MFT angle less than −12° with varus stress, less than −5° with valgus stress, and/or extension deficit greater than 5°. The results show that post-operatively, the mean MFT angle is maintained within a narrow range (−1° to −7° with varus stress, 4° to −3° with valgus stress). 5/57(9%) patients had a mean MFT angle of 6.4°(0° to 7°) with valgus stress, and were considered to have been over-corrected. There were no extension deficits.
The purpose of the study was to evaluate if 2 week Levine score can provide an adequately responsive outcome measure in Carpal Tunnel Decompression by comparing it with 6 month score. The treatment outcome of 300 patients with Carpal Tunnel Decompression was determined by using Levine score at 2 weeks and 6 months after surgery. The mean age of patients was 55 years and 6 months, 71.3% (214) were female with 55.33% (167) operations being performed on right hand. All patients were scored through Levine questionnaire pre operatively and at 2 weeks and 6 months from date of surgery. The correlation between the scores was evaluated. Although statistical significance was found between the pre operative score and the scores at both 2 weeks and 6 months, no statistical difference was found between the scores at 2 weeks and 6 months post surgery. Multiple regression analysis with the 2 week–6 month score difference as the dependable variable shows a predictable outcome at 2 weeks. We conclude that the Levine score at 2 weeks is a reliable, responsive and practical instrument for outcome measure in Carpal Tunnel Surgery. It coincides with suture removal and provides a convenient and predictive assessment of the medium term results in a high percentage of treated patients.
The accuracy of measurement in computer-assisted total knee arthroplasty is dependent on the quality of data acquisition at the start of the procedure; errors in landmark identification could lead to misalignment and therefore poorer longterm outcomes. Some navigation systems require the surgeon to explicitly identify the femoral epicondyles in order to calculate the trans-epicondylar axis, whereas other systems are able to interpolate the epicondylar location based on a number of points acquired from the distal femoral surface. Significant inter-observer variability in landmark identification has been previously reported in dry bone studies. The purpose of this study was to test the accuracy of identification of the epicondyles during a simulated total knee replacement on a fresh cadaveric specimen. An unfixed fresh cadaveric left lower limb was used to perform a navigated total knee replacement using the Orthopilot® (B|Braun-Aesculap, Tuttlingen, Germany) image-free navigation system. Sixteen surgeons attending an advanced navigation training course were invited to take part. A single consultant surgeon performed initial dissection and pin placement, up to the point of landmark acquisition. Each subject was then asked to use a pointer tool to identify the medial and lateral epicondyles, as they would in an operative situation. Data were recorded by the Orthopilot® system, and exported as a 3D array for further analysis. Initial visualisation with a 3D scatter plot showed that points were evenly distributed within a circular pattern around each epicondyle. The length of a vector between each point on each epicondyle was calculated in turn. The maximum distances between points were 15.6mm for the medial epicondyle, and 19.9mm for the lateral epicondyle. We then calculated the length and angulation of the trans-epicondylar axis (TEA) for each observer, equivalent to the vector between each pair of points (medial and lateral epicondyle). An average TEA was calculated, and the range and standard deviation of angulation were determined. In the x axis the range was 16.3° (–8.3° to 7.9°, SD 5.1°), in the y axis the range was 18.7° (–8.7° to 10°, SD 5.2°) and in the z axis the range was 20.5° (–10.1° to 10.4°, SD 6.5°). Range of recorded TEA length was 64.5 to 74.9mm (mean 70.6mm, SD 3.3mm). We conclude that in this simulated operative scenario, surgeons exhibited considerable variability when locating the epicondyles. Range of angulation of the TEA exceeded 16° (SD >
5.1°) in all 3 planes. We cannot recommend the use of a trans-epicondylar axis determined from 2 single points, as a reliable landmark in navigated total knee replacement.
Total knee replacement (TKR) has become the standard procedure in management of degenerative joint disease with its success depending mainly on two factors: three dimensional alignment and soft tissue balancing. The aim of this work was to develop and validate an algorithm to indicate appropriate medial soft tissue release during TKR for varus knees using initial kinematics quantified via navigation techniques. Kinematic data was collected intra-operatively for 46 patients with primary end-stage osteoarthritis undergoing TKR surgery using a CT-free navigation system. All patients had preoperative varus knees and medial release was made using the surgeon’s experience. From this data an algorithm was developed to define the medial release based on the pre-operative mechanical femoral-tibial angle with valgus stress; No release (tibial cut only) when valgus stress >
−2/3°. Moderate release (medial aspect of tibia +/− semimembranosous tendon) when valgus stress >
−5° and <
−2°. Extensive release (proximal) when valgus stress <
−5°. If there was a fixed flexion deformity >
5° then a posterior release was performed. This algorithm was validated on a further set of 35 patients where it was used to determine the medial release based only on the kinematic data. The post-operative varus and valgus stress angles for the two groups were compared and showed good outcomes in terms of distribution and outliers. The results showed that the algorithm was a suitable tool to indicate the type of release required based on intra-operatively measured pre-implant valgus stress and extension deficit angles. It reduced the percentage of releases made and the results were more appropriate than the decisions made by an experienced surgeon.
Performing Total Knee Replacement (TKR) surgery using computer assisted navigation systems results in more reproducibly accurate component alignment. Navigation allows real time evaluation of passive knee behaviour throughout flexion. These kinematic measurements reflect tibial rotation about the femoral condyles, patellar tracking and soft tissue balance throughout surgery. In this study, we aim to study dynamic knee function in navigated and standard instrumentation TKR patients performing a range of everyday activities using gait analysis. A prospective randomised controlled trial evaluated the functional outcome using gait analysis with 20 patients in each of three groups – Standard, Navigated and Control. The same implant (Scorpio) and navigation system (Strykervision) was used for each patient. The control group were subjects with no history of knee pathology or gait abnormality. Using an 8-camera Vicon motion analysis system set at 120Hz (real-time motion), we assessed the following functional activies: walking, rising from/sitting in chair, ascending/descending stairs. One functional outcome measure we have analysed so far is the maximum flexion angle. The maximum flexion angle was recorded for each activity in standard, navigated and control groups respectively. ANOVA was performed, with significance set at p<
0.05. Maximum flexion angle during gait was 65.6°, 72.6° (p=0.009) and 73.5° (p=0.74), chair rising/sitting was 82.5°, 92.8° (p=0.01), and 93.5° (p=0.64), stairs ascent/descent was 81.8°, 99° (p<
0.0001), and 113.4° (p<
0.0001). In terms of dynamic functional outcome, we found that the average maximum flexion angle for the navigated group was greater than for the standard group; moreover, this was similar to the maximum flexion angle for the control group when performing a variety of normal daily activities.
We prospectively studied 15 proximal tibial and 30 distal femoral fractures treated with the Less Invasive Stabilisation System for periarticular fractures about the knee. Of these 45 fractures, one patient returned to Russia and was thus lost to follow up. The mean age of the remaining patients was 64.4 years (range 15–94 years). There were 26 females and 13 males. All fractures were classified according to the AO classification. We found the use of temporary external fixation and mobile radiolucent wedge leg supports very helpful during surgery for these cases. We developed an increasingly aggressive postoperative mobilisation regime with increased experience of using this fixation technique. Functional assessment was performed using the Schatzker and Lambert scores. The average time to union was 14.78 weeks (range 10– 28 weeks). 43 fractures have united with one fracture showing signs of delayed union. There were two implant failures, two deep vein thrombosis and two compartment syndromes. Five patients died of unrelated causes and without problems relating to their fracture. We conclude that the Less Invasive Stabilisation System is a satisfactory method of treating these complex and difficult fractures about the knee with a high rate of union and good functional outcome.
Elevated serum cobalt and chromium ion levels associated with carcinogenesis and chromosomal damage in animals have raised concerns that metal-on-metal (MOM) total hip replacement (THR) in humans may produce the same effects over time. Considering that the risks may be related to the level of these ions in the body, this study compared the serum cobalt and chromium ion levels in patients with unilateral versus bilateral 28 mm diameter MOM THR. All patients having THR at our institution were prospectively registered on a computerised database. From our database, we identified 108 patients with Ultima (Johnson and Johnson, Leeds) MOM THR with 28 mm bearing made of cobalt-chromium alloy. After patient review in clinic and before blood results were known, patient matching was performed by date after surgery at blood sampling, activity level and body mass. Using these stringent criteria, 11 unilateral THR could be adequately matched with 11 bilateral THR. Blood serum was taken with full anti-contamination protocols and serum analysed via inductively coupled plasma mass spectrometry. The serum cobalt ion level after unilateral MOM THR was 4.4 times normal (median 22 nmol/L, range 15 to 37 nmol/L) compared to 8.4 times normal (median 42 nmol/L, range 19 to 221 nmol/L) for bilateral MOM THR (p=0.001). The serum chromium ion level after unilateral MOM THR was 3.8 times normal (median 19 nmol/L, range 2 to 35 nmol/L) compared to 10.4 times normal (median 52 nmol/L, range 19 to 287 nmol/ L) for bilateral MOM THR (p=0.04). This study has shown that the serum cobalt and chromium ion levels in patients with bilateral MOM THR are significantly higher than those in patients with unilateral MOM THR. With levels of up to 50 times the upper limit of normal, this finding may be of relevance for the potential development of long-term side effects.
The majority of diaphyseal forearm fractures in children are treated by closed reduction and plaster immobilisation. There is a small subset of patients where operative treatment is indicated. Recent reports indicate that elastic intramedullary nailing (EIN) is gaining popularity over plate fixation. We report the results of EIN for diaphyseal fractures of the forearm in 44 children aged between 5 and 15 years during a three-year period. The indications were instability (26), redisplacement (14), and open fractures (4). Closed reduction and nailing was carried out in 18 cases. A single bone had to be opened in 16 cases and in 10 cases both bones were opened for achieving reduction. Out of the 39 both bone forearm fractures, 35 patients had stabilisation of both radius and ulna and in 4 cases only a single bone was nailed (Radius 3, Ulna 1). Union was achieved in all the 44 cases at an average time of 7 weeks with one delayed union. All patients regained full flexion and extension of the elbow and wrist. Pronation was restricted by an average of 20° in 30% patients. Complications were seen in 10 patients (20%). 4 patients had prominent metal work which required early removal. There was refracture in one case, which was treated by nail removal and re-fixation. Two patients developed post operative compartment syndrome requiring fasciotomy. EIN of the radius alone in a patient with fractures of both the bones of forearm, led to secondary displacement of the ulna. This resulted in ulnar malunion and a symptomatic distal radio-ulnar joint subluxation. This was successfully treated by ulnar osteotomy. Compared to forearm plating EIN involves minimal scarring, easier removal and less risk of nerve damage. We therefore recommend EIN for the treatment of unstable middle and proximal third forearm fractures.
The experimental determination of residual stress fields on the surface of retrieved femoral heads represents a fundamental step in understanding their wear degradation behavior and the tribological mechanisms, which are operative on the femoral joint during its working life time. In this work, the surface of retrieved alumina and zirconia (Al2O3 and ZrO2) femoral heads were investigated by piezo-spectroscopic tecniques based both on photoluminescence and Raman effects. The high spatial resolution of the laser, impinging on the investigated surface (typically about 1 micron of lateral resolution), enabled us estimating patterns and magnitude of residual stress in extremely narrow zones, comparable with the grain size of the material. Four retrieved ceramic femoral heads were analyzed. Two balls were made of alumina with a typical grain size of from 4 to 10 microns. Both alumina balls were retrieved after only few years from implantation, due to septic and aspetic loosening. The remaining two femoral heads were made of zirconia with a typical grain size of 1 micron. These latter balls were retrieved after 2 and 13 years, respectively (both for loosening problems). With a systematic collection of a large number of data on a microscopic level it was possible to assess the retrieved femoral heads in to to, thus extending the microscopic analysis to the entire joint. In allumina balls retrieved after short time implantation, a macroscopic stress field was found, which arose from manufacturing, loading history, and the displacements acting on the femoral head during its lifetime. This stress field was completely overcome by a microscopic residual stress field due to local contacts (e.g., local shocks owing to microseparation, impinging and wear contacts). On the other hand, in zirconia femural heads, the major amount of surface deterioration after long-term exposure arose from tetragonal-to-monoclinic transformation in biological environment. These data allowed us to draw interesting considerations about the role of the material microstructure and the peculiar kinematic mechanisms involved with the use of femoral heads made of different materials. Spectroscopic techniques, which are complementary to in vitro testing procedures and stress analyses based on finite-element methods, can be very useful for improving the design of the femoral head and for optimizing the microstructural characteristics of the ceramic materials employed. Based on this and previous fluorescence and Raman spectroscopic studies, we also propose that a systematic screening of the ceramic implants before implantation can strongly reduce the probability of failure of the implant.
Alumina ceramic has been used in total hip arthoplasty since the 70’s and, in the last 30 years, a considerable evolution has occurred in designing the microstructural features of this material, taking advantage of improved processing techniques, as the hot isostatic pressing. As a result, a high degree of densification (>
99.5) has been achieved in materials with a high degree of purity and, especially, with a fine grain size ( 2 microns). The surface stress field acting on a femoral head inoperation is not only due to working conditions, but also to unexpected factors, as local impacts on the surface as a result of partial dislocations, formation of debris, etc. These additional factors greatly contribute to activate degradation mechanisms which, unfortunately, may lead to failure of the implant. In this study, five alumina femoral heads were investigated, which were retrieved from patients after different periods of time. Among those investigated femoral heads, two belonged to a first-generation type of alumina material with a relatively coarse grainsize (average value 8 microns) and were retrieved due to surface degradation after long periods of implantation (19 and 17 years, respectively); the remaining three implants analyzed were instead recently manufactured implants with a fine grain size; they were retrieved after relatively short periods because of different causes as, for example, cup or stem loosening. Surface stress analysis using the luminescence of Cr3+impurity in alumina was performed on the retrieved femoral heads and a statistical comparison was attempted among implants with different microstructural characteristics. The investigation led to estimate average residual stress and statistical stress distributions as a function of the location on the femoral head. The analysis was performed both on the very surface and in the sub-surface of the head, using the confocal and the through-focus configurations of the optical spectrometer, respectively. Different statistical distributions of residual stress were observed in alumina femoral heads with different grain sizes and models were created to understand their dependence on processing and surface loading.
Metal-on-metal (MOM) bearings after total hip arthroplasty are known to elevate the serum concentrations of metal ions, raising concerns about the long-term effects. One potential modifier of ion release is the bearing diameter used. Resurfacing MOM bearings have a large surface area available for corrosion compared to the typical bearing size of 28 mm in total hip replacement (THR) but may benefit from improved lubrication and reduced production of corrodible wear debris. The net effect of these two variables on metal ion release is unknown. In this study, we compared the level of ion release in patients after large bearing MOM hip resurfacing arthroplasty with patient after small bearing MOM THR. We measured the serum cobalt and chromium levels from 22 patients with large bearing diameter MOM hip resurfacing arthroplasty (Cormet 2000 and Birmingham Hip Resurfacing) and compared them to the serum cobalt and chromium levels of 22 patients with small bearing diameter (28 mm) MOM THR (Ultima). Patients were prospectively matched for activity level, body mass and date after surgery at blood sampling. All were at least 6 months after surgery. We found the median cobalt and chromium levels after hip resurfacing arthroplasty to be 7.6 times normal (median 38 nmol/L, range 14 to 144 nmol/L) and 10.5 times normal (median 53 nmol/L, range 25 to 165 nmol/ L) respectively. This is compared to 4.4 times normal (median 22 nmol/L, range 15 to 87 nmol/L) for cobalt and 3.8 times normal (median 19 nmol/L, range 2 to 58 nmol/L) for chromium after 28 mm MOM THR (p=0.0021 and p<
0.0001).
Prior studies have compared the bacterial load observed in laminar flow operating theatres (LFOTs) and standard operating theatres (STOTs) by wound culture and air sampling during surgery. However many organisms responsible for low grade infection after THR are not readily identified on routine culture and may be detectable only by more sensitive techniques such as the poly-merase chain reaction (PCR). This study assessed the wound contamination rate during THRs and compared the results in STOT with that in LFOTs using PCR. We recruited patients undergoing primary THR for osteoarthritis. Surgery was performed in either STOTs or LFOTs, using identical skin preparation solutions, surgical drapes and operating attire. Specimens of the deep tissue, taken at the beginning and end of surgery, were each immediately separated into two sterile containers, one sent for culture (aerobic, anaerobic and enriched meat broth) and the other frozen at minus 80 degrees Celsius for PCR at a later date. In each theatre type, 40 specimens from 20 THRs were analysed by both PCR and culture. Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs, of which 3 were taken at the start of surgery and 9 at the end of the surgery, giving a 45% wound contamination rate (9 of 20). Two specimens (5%), both taken at the end of surgery, were positive on enriched culture. In LFOTs, bacterial DNA was identified by PCR on 8 of 40 specimens (20%), of which 2 were taken at the start of surgery and 6 at the end of surgery, giving a 30% wound contamination rate (6 of 20). No specimens were positive on enriched culture. Wound contamination of primary THR occurs frequently in both STOTs and LFOTs. Although STOTs showed evidence of more frequent wound contamination than LFOTs, with the numbers available, no significant difference was detected. These data remind us the importance of aseptic surgical technique as significant wound contamination can occur despite the use of ultra clean air operating theatres.
Distal tibial fractures may be satisfactorily held in reduction by fine-wire external fixation techniques, avoiding the need for open reduction and internal fixation. However, as the use of external fixation is associated with pin-site infection, extra-articular placement of the wires is recommended. This study assesses the proximal extension of the capsule of the ankle joint in order to provide information on the safety of wire placement for distal tibia fractures. We recruited 7 patients who were electively scheduled for an MRI ankle investigation with the suspicion of osteochondral defect and/or meniscoid lesion. Patients with a history of ankle fracture or ankle surgery were excluded from the study. Just prior to MRI, the ankle joint was injected with 5 to 15 ml of contrast solution (1 mM dimeglumine gadopentetate). Selected fat-saturated T1-weighted MRI scans with sagittal, coronal and axial views were obtained. The site and proximal extent of the capsular reflection with reference to the anterior joint line were measured. All contrast-enhanced MRIs of the ankle joint space were well defined and unambiguous. Proximal capsular extensions above the plane of the anterior joint line were noted at the antero-medial and antero-lateral aspect of the joint (mean 8.9 mm, range 4.9 to 13.4 mm) and at the tibia-fibular recess (mean 18.7 mm, range 13.3 to 23.6 mm), areas that are frequently traversed by wire insertion. Conclusion: This in vivo contrast-enhanced MRI ankle study demonstrates an appreciable capsular extension above the joint line of the ankle. The proximal capsular extensions at the antero-medial and antero-lateral aspect of the joint and at the tibio-fibular recess run the risk of being traversed during fine-wire placement for distal tibia fractures. Surgeons using these techniques should be aware of this anatomy.
Zirconia (ZrO2) on Polyethylene (PE) has been used for18 years. However, a majority of clinical results expressed caution, citing surprisingly high wear and osteolysis. The most recent clinical study (Walters 2004) reports 20% higher wear with ZrO2/PE compared to CoCr/PE The PE wear may be the result of increased surface roughness of the ball, due to zirconia transformation from tetragonal to monoclinic phase. Impingement of metal cup backing on zirconia may result in high stress that drives the transformation. Our objective was to simulate the conditions most likely to transform the zirconia ball surface. In phase one, the rim of a titanium cup was loaded against a zirconia ball with a static load range of 0.01kN to 10kN to simulate impingement-dislocation stress. The ball was cleaned with acid, ultrasonic cleaning, and then observed under SEM. Ball sections were made for XRD study. In phase two, the zirconia balls were pressure stressed in a hip simulator (static load range of 1kN to 4kN) for 600 cycles. Wear studies follow. In phase one, the rim of a titanium cup was loaded against a zirconia ball with a static load range of 0.01kN to 10kN to simulate impingement-dislocation stress. The ball was cleaned with acid, ultrasonic cleaning, and then observed under SEM. Ball sections were made for XRD study. In phase two, the zirconia balls were pressure stressed in a hip simulator (static load range of 1kN to 4kN) for 600 cycles. Wear studies follow. Pressure alone does not appear to transform zirconia in the articular surface. The phase two simulator studies include combinations of mechanical stress, environmental aging (autoclave) and lubricants (air, water, serum). The role of the heavy metal transfer may actually protect the zirconia surface from transformation phenomena.
Idiopathic osteoarthritis (OA) is a complex, late-onset disease whose causes are still unknown. In spite of tremendous efforts, the search for the genes pre-disposing towards osteoarthritis has so far met with little success. We hypothesize that epigenetic changes play a major role in the pathology of OA. Epigenetics refers to stable, heritable, but potentially reversible modifications of gene expression that do not involve mutations in the DNA sequence, for example DNA methylation or histone modification. Epigenetic changes are gene and cell-type specific, may arise sporadically with increasing age or be provoked by environmental factors. To investigate whether epigenetic changes are significant factors in OA, we examined the DNA methylation status of the promoter regions of three genes that are expressed by OA, but not by normal, articular chondrocytes, namely MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and MMP-13 (collagenase3). We hypothesized that these genes are silenced in normal chondrocytes by methylation of the cytosines of CpG dinucleotides in the respective promoter regions, but that abnormal expression is associated with a de-methylation, leading to eunsilencing f of gene expression. Cartilage was obtained from the femoral heads of 16 OA and 10 femoral neck fracture (#NOF) patients, which served as controls due to the inverse relationship between osteoporosis and OA. The cartilage was milled in a freezer mill with liquid nitrogen, DNA was extracted with a Qiagen kit, digested with methylation sensitive restriction enzymes, followed by PCR amplification. These enzymes will cut at their specific cleavage sites only if the CpGs is not methylated and thus allow us to determine methylation status of specific CpG sites.
In osteoarthritis (OA) there is a loss of matrix components, especially aggrecan, which is a major structural component important for the integrity and function of articular cartilage. The breakdown of aggrecan is mediated by enzymes from the ADAM-TS (a disintegrin and metalloproteinase with thrombospondin motifs) family and recent studies have suggested that, in humans, ADAM-TS4 (aggrecanase-1) plays a major role. Articular chondrocytes do not express ADAM-TS4 in contrast to clonal OA chondrocytes. Since in any somatic cell non-expressed genes are thought to be silenced by DNA methylation in the promoter region, the aims of the project were twofold:
to localize enzyme expression for ADAM-TS4 by immunocytochemistry and to determine whether ‘unsilencing’ (i.e. DNA de-methylation) in the promoter of ADAM-TS4 was associated with the abnormal enzyme synthesis. Using immunocytochemistry, we confirmed that there is an increased expression of ADAM-TS4 in OA chondrocytes, which initially occurs in chondrocytes of the superficial zone. As the Mankin score increases, ADAM-TS4 positive chondrocytes were found in duplets, then quadruplets until, at Mankin score >
10, all the cells in a typical OA clone were immunopositive for ADAM-TS4, suggesting that abnormal enzyme expression was inherited by daughter cells. DNA was extracted from femoral head cartilage of 24 patients, who had undergone hip replacement surgery for either symptomatic OA or following a fracture of neck of femur (#NOF). The latter was used as control due to the inverse relationship between OA and osteoporosis. For OA samples, it was important to sample only those regions for which immunocytochemistry had shown the presence of ADAM-TS4 synthesizing cells, i.e. the superficial zones near the weight-bearing region. DNA methylation only occurs at cytosines of the sequence 5′...CG...3′, the so-called CpG sites. To determine methylation status of specific CpG sites, methylation sensitive restriction enzymes were used, which will only cut DNA in the absence of methylation. By designing PCR primers that bracketed these sites, presence or absence of PCR bands could distinguish between methylated and non-methylated CpGs respectively. The ADAM-TS4 promoter contains a total of 13 CpG sites. Using restriction enzyme/primers combinations, it was possible to analyze 7 of these sites for methylation status. In the control group, all 7 CpG sites were methylated, while there was an overall 49% decrease of methylation in the OA group (p=<
0.0001). Some of the CpG sites were more consistently demethylated then others, one site at −753bp upstream from the transcription start site, showed a 86% decrease in methylation in OA compared to the control group (p=0.0005), while at other sites the decrease in methylation ranged from 36–50%. Conclusions. This study confirmed by immunocytochemistry that ADAM-TS4 is produced by OA chondrocytes, contributing to the degradation of their matrix. This abnormal enzyme expression is associated with DNA methylation. If a causal relationship could be proven in the future, then DNA de-methylation might play an important role in the pathogenesis of osteoarthritis and future therapies might be directed at influencing the methylation status.
Clonal chondrocytes of osteoarthritic (OA) cartilage express an aberrant set of genes. We hypothesize that this aberrant gene expression may be due to clonally inherited epigenetic changes, defined as altered gene expression without changes in genetic sequence. The major epigenetic changes are due to altered DNA methylations in crucial parts of the promoter region. If the cytosines of CpG dinucleotides are methylated, the gene will be silenced, even if the right transcription factors are present. Similarly, de-methylations may activate previously silenced genes. Our aims were to provide ‘proof-of-concept’ data by examining the methylation status of genes in OA vs non-OA chondrocytes. Articular cartilage was obtained a) from the cartilage of fracture-neck-of-femur (#NOF) patients and b) from or around the eroded regions of OA samples. The former was full thickness cartilage, the latter was partially degraded cartilage, which contained mostly clonal chondrocytes as confirmed by histology. The cartilage samples were ground in a freezer mill (Glen Creston, UK) and DNA was extracted with a Qiagen DNeasy maxi kit. To assess DNA methylation status, the genomic DNA was treated overnight with methylation-sensitive restriction enzymes. Cleavage of selected sites was detected by PCR amplifications with primer pairs designed to bracket selected promoter regions. Loss of the PCR band after digestion with the enzymes indicated absence of methylations, whereas presence of the band indicated methylated cytosine. We selected MMP-9 as one of genes that is activated in OA. Transcription of mmp-9 is regulated by a 670 bp sequence at the 5′-end flanking region, which contains 6 CpGs and a further 21 CpGs within the 1.5 kb region further upstream. A PCR primer pair was designed to bracket a 350bp sequence upstream from the transcription start site of mmp-9, which contained four of the six potential methylation sites, cleaved by the methylation-sensitive enzymes AciI and HhaI. DNA from 9 OA patients, 5 #NOF patients and 1 rheumatoid arthritic (RA) patient were digested with HhaI or AciI and examined for the presence or absence of PCR bands. In all patients, digestion with HhaI abolished the PCR band, indicating that the HhaI site was never methylated in either #NOF or OA patients. However, a remarkable difference was found after digestion with AciI: in 8/9 OA patients, the PCR band was no longer detectable, while in 4/5 #NOF patients the PCR band was still present. This suggested that all three AciI cleavage sites were methylated in the majority of chondrocytes from #NOF patients, while at least one of the three AciI cleavage sites was unmethylated in OA patients. Interestingly, the PCR band was present in the RA patient, suggesting methylation of the AciI cleavage sites. The present study provides the first ‘proof-of-concept’ data that suggest epigenetic changes may play a role in the etiology of osteoarthritis. Clearly further work is required to establish the generality of the present findings and whether de-methylations are also found in the promoter regions of other genes that are aberrantly expressed in OA.
Our findings indicate that b-FGF and perhaps, more interestingly, MMP-9 are implicated in the activation of the angiogenic ‘switch’ at the chondroepiphysis leading to vascular invasion. The fact that MMP-9 can act as a stimulator to angiogenesis is a novel finding. The mechanism of action remains unclear although it is possible that it is involved in the deactivation of inhibitors of vasculogenesis or the activation of angiogenic factors, or both.
This study examines the effect of injecting an inert synthetic lubricant, perfluoroalkylether (PFAE16350), as a mechanical joint lubricant to prevent the development of osteoarthritis in a surgically induced model of osteoarthritis in the adult guinea pig.
After wound closure, the animals were randomly assigned to 1 of 2 groups: (1) Single intra-articular injection of 1ml synthetic, sterile lubricant (PFAE16350) or (2) Control group with single intra-articular injection of 1ml 0.9% sterile saline. At 9 weeks after surgery, after sacrifice, knee arthrotomy was performed, the presence of synthetic lubricant noted and the articular cartilages examined for macroscopic evidence of osteoarthritis. These cartilages were then fixed, embedded, sectioned, stained and graded histologically for osteoarthritis according to a modified Mankin scoring system. Immunohistochemical studies were performed to assess for any inflammatory or cytotoxic effect by the lubricant.
Subjective macroscopic assessment of the medial tibial plateau osteophyte was noted to be larger and the articular surface more roughened in the control cases compared to the lubricated cases. Synthetic lubricant was noted at arthrotomy in all cases where it was injected. Guinea-pig joints treated with the synthetic lubricant showed a mean modified Mankin score of 3.0 points compared with the guinea-pig joints treated with saline where the median modified Mankin score was 8.5 points (p<
0.001). There was no evidence of an inflammatory or cytotoxic response by immunohistochemical studies.
A 12 year old girl presented with a history of intermittent pain in her left knee since she started walking. She was seen in the vascular clinic due to engorged veins in her left leg and was diagnosis of Klippel-Trenaunay syndrome was made. Her knee pain worsened and an orthopaedic opinion was obtained. A history of repeated knee effusion and swelling was noted. Examination revealed partial gigantism of the left leg and reduced range of motion of the knee. There was soft tissue swelling of the knee with no effusion. Blood investigations were normal. X-rays showed an arthritic joint. MRI scans revealed synovial thickening and a vascular malformation suggesting a synovial haemangioma. She underwent Radical Open Synovectomy and excision of the haemangioma. Blood loss was minimal. Extensive haemosiderin deposition was noted along with Grade IV arthritic changes. Postoperative recovery was uneventful. Surgeons have been reluctant to excise synovial hemangiomas due to the risk of haemorrhage. A recent paper from Switzerland suggested excision was possible with minimal blood loss. Haemosiderin deposition due to recurrent haemarthrosis may predispose to articular damage. We recommend early excision of synovial haemangiomas to minimise articular damage.
The quality performance of a Bone Bank depend on a full time bone bank co-ordinator, identification of donors, retrieval and harvesting of grafts, blood and microbiological assessment, medical supervision for decisions about contaminated grafts, a strict follow-up protocol and a regular audit of bone bank (Ivory and Thomas 1993). We also suggest that regular correspondence to the consultant using the bone grafts will improve the accuracy of follow-up.
The use of designer scaffolds to deliver biologically active osteogenic growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) to the sites of tissue regeneration in for example orthopaedics, has tremendous therapeutic implications. The aims of this study were to generate biomimetic biodegradable porous osteogenic scaffolds using a supercritical fluid process to encapsulate rhBMP-2, and to examine the ability of the scaffolds to promote human osteoprogenitor differentiation and bone formation in vitro and in vivo. The rhBMP-2 encapsulated in Poly(-lactic acid) (PLA) scaffolds (100ng/mg PLA) were generated using an innovative supercritical fluid mixing method. The bioactivity of rhBMP-2 encapsulated PLA scaffolds were confirmed by induction of the C2C12 promyoblast cell line into the osteogenic lineage as detected by alkaline phosphatase expression. No induction of alkaline phosphatase-positive cells was observed using blank scaffolds. BMP-2 released from encapsulated constructs promoted adhesion, migration, expansion and differentiation of human osteoprogenitor cells on 3-D scaffolds. Enhanced matrix synthesis and cell differentiation on growth factor encapsulated scaffolds was observed following culture of human osteoprogenitors on explants of chick femoral bone wedge defects in an ex vivo model of bone formation developed using the chick chorioallantoic membrane model. In vivo studies using diffusion chamber implantation and subcutaneous implantation of human osteoprogenitors on rhBMP-2 encapsulated scaffolds showed morphologic evidence of new bone matrix and cartilage formation in athymic mice as assessed by x-ray analysis, immunocytochemistry and birefringence. These studies provide evidence of controlled release of BMP-2 from biodegradable polymer scaffolds initiating new bone formation in vivo. The generation of 3-D biomimetic structures incorporating osteoinductive factors such as BMP-2 indicates their potential for de novo bone formation that exploits cell-matrix interactions and, significantly, realistic delivery protocols for growth factors in musculo-skeletal tissue engineering.
Using PCR, bacterial DNA was identified on 12 of 40 specimens (30%) from STOTs. Of these 12, three were taken at the start of surgery and nine at the end of the surgery, equivalent to a 45% wound contamination rate (9 of 20). Only two specimens (5%), both taken at the end of surgery, were positive on enriched culture. In LFOTs, bacterial DNA was identified by PCR on eight of 40 specimens (20%). Of these eight, two were taken at the start of surgery and six at the end of surgery, equivalent to a 30% wound contamination rate (6 of 20). None of the specimens were positive on enriched culture.
Statistical analysis used the Mann-Whitney U test.
Alumina has been the dominant ceramic used in orthopaedics since 1970. It is near diamond hardness is superior to all other biomaterials and its wettability has been a great benefit for tribological reasons. Over the past 30 years, this ceramic has gradually been optimized with superior processing, higher purity, greater density, and somewhat higher strength. Also serial numbers have been added to uniquely identify implant components and proof-testing now ensures that every implant is pre-clinically tested, compared to prior methods of sampling only 2–3% for destructive tests. The clinical downside remaining has been the small but troublesome fracture incidence of alumina implants. Historically, this has averaged 0.015% (15 per 100,000 cases) overall but varied from 0.08% up to 13% in those clinical series experiencing fractures (Heros, Sem. Arthrop-98). As well as creating patient hardships, fracture of any implant in the USA frequently leads to major lawsuits. Thus ceramic implants must be treated w While there has as yet been no FDA-approval given to market ceramic cups in the USA, there are a number of ceramic candidates being developed for both THR and TKR. These include zir-conia-alumina composites as well as new zironia/zirconia or zirconia/alumina combinations for THR. In addition, there are new combinations of toughened aluminas and also other choices such as silicone nitrides proposed for use with either metal CoCr heads or CoCr cups. Finally an alternate approach has been to provide a metal zirconium knee joint with a ceramic zirconia coating for improved bearing performance. Thus, the state of the art of alumina implants will be reviewed and put into perspective with the “new and improved” ceramics currently on the horizon. This survey will put into perspective the physical and mechanical attributes as well as the clinical performance of ceramic implants.
Major long-term complication of total hips is osteolysis in the more active patients. Osteolysis is a result of the biological response to the wear debris particles. This has resulted in the search for improved bearings such as metal and ceramic on polyethylene, all ceramic, and all metal total hips. Wear ranking of metal-polyethylene, ceramic-polyethylene, metal-metal, and ceramic-ceramic total hips has become clear at ratios of 1,000:500:10:1. However, wear debris from polyethylene, ceramic, and metal wear tests average about 0.6, 0.3, and 0.02 microns, respectively. From this information we can now deduce the number of particles librated is millions for ceramics, billions for polyethylene, and trillions for metal. In recent years, studies have revealed new information on the biological response to various types of wear debris. Factors such as number of particles, particle morphology (size and shape), and surface to volume ratio are becoming keys to a partial comprehension of this biological response and osteolysis. Recent studies have demonstrated that smaller particles (<
0.1 microns) may be more toxic to cells than larger particles (>
0.1 microns). Studies have shown that crosslinking of polyethylene reduces the size of the wear debris particles and that for gamma irradiated polyethylene this reduction in size is proportional to the radiation dose. It has also been shown that crosslinking results in a significant reduction in fibril particles. Therefore, large reductions in wear rate do not necessarily mean that the total joint will be more successful. Thus, two factors, which interact, are the volume rate of wear and the morphology of the wear debris particles. Some investigators have developed a biological ind
Ceramic on ceramic hip-joint replacements (THR) are known for their excellent wear resistance. Such rigid-rigid bearings generally exhibit a biphasic wear-performance, i.e. a rapid run-in phase decreasing into a steady-state phase. However, due to the ultra-low wear of ceramics, few studies have adequately characterized these wear phases. Since this behavior was not well defined for modern alumina-on-alumina hips, we studied this phenomenon using hip simulator techniques. We also compared all-ceramic THR to UHMWPE wear-rates for exact comparison. Run-in wear was measured at 200,000 cycle intervals to 1 million cycles (1 Mc) followed by 500,000 cycle intervals to 14 Mc. Alumina heads started off with high wear but then demonstrated a curvilinear run-in phase that smoothly transited into steady-state wear. The alumina liners had linear run-in to 0.6 Mc and then abruptly transited into steady-state by 0.8 Mc. During run-in, the liner wear was 40% greater than for the mating heads. Steady-state liner wear varied from 0.002 to 0.007 mm3/Mc. It was also clear that at least 10 million cycles were required to define the steady-state wear for alumina implants due to their ultra-low wear magnitudes. Combined head and cup run-in wear averaged 0.33 mm3/Mc and was completed within 0.8 Mc while steady-state wear was <
0.01 mm3/Mc up to 20 Mc. This was a remarkable 30-fold reduction from run-in. The run-in phase would probably be completed by the first year of follow-up. Compared to UHMWPE cups, the alumina implants demonstrated a 9,000-fold wear-reduction over 20 million cycles in the simulator. This may correspond to 20 years in the typical patient. In addition, the alumina/UHMWPE combination has been favored historically because using CoCr/ UHMWPE bearings resulted in a doubling of the wear-rates in comparative clinical studies. Clearly the all-ceramic THR offers a much superior alternative with its massive reduction in wear-debris volume.
Lubricated metal-on-metal (MOM) bearing surfaces are not easily separated, unlike ceramic- or metal-on-UHMWPE (COP, MOP), due to interfacial forces and low diametric clearance that provides a ‘suction-fit’. In vivo videofluoroscopic studies have shown that patients with MOP/COP THRs exhibit separation of bearing surfaces by up to 3.1 mm during normal gait and 5.4 mm during active abduction while patients with MOM bearings do not. In this regard, MOM bearings may have similarities to constrained bearings with the potential to lower dislocation rates. All patients under 70 years old undergoing primary THRs for primary osteoarthritis were prospectively registered on a computer database. From 1993–8, patients were offered a 28 mm COP bearing. After 1998, as part of a clinical trial, a 28 mm MOM bearing was inserted instead. For all cases, we used a metal-backed, uncemented acetabulum allowing a modular 10-degrees posteriorly augmented insert (Duraloc/PFC/Ultima, J&
J) and the same cemented femoral stem (Ultima, J&
J). The same experienced surgeon performed all operations using the posterior approach. Interfacial forces between bearing surfaces were assessed in vitro with a variable-speed-motor winch (APT) and a load-cell (E375/RDP) by recording peak-retaining-forces of bearing couples during separation with variable impact-distraction velocities. Statistical analysis used the Chi-square and student’s t-test. We identified 140 COP THRs in 129 patients and 109 MOM THRs in 100 patients. Nine of 140 (6.4%) COP bearings dislocated within 3 months of surgery compared to 1 of 109 (0.9%) in the MOM group (p=0.024). No significant differences were identified between groups when comparing patient and prosthesis factors. In vitro assessment demonstrated that MOM bearing possessed interfacial retaining forces up to 30N more than COP bearing (p<
0.001). This study demonstrates a significantly lower dislocation rate in THR with MOM bearing compared with COP. A potential explanation is the differential ease of separation that the two lubricated bearing couples possess due to interfacial retaining forces (viscous tension and ionic adhesive forces) exerted by the lubricating fluid.
According to the knee simulator test results in 1970s, the total decrease in thickness of UHMWPE tibial tray in combination with ceramic femoral component [F-Comp] was less than one tenth as that of the combination with metal [ The retrieved TKP was implanted in 1979, and retrieved on January 9th in 2002. This TKP consisted of an alumina ceramic F-Comp and a UHMWPE tray combined with a alumina ceramic tibial component. Observations of the surface of alumina F-Comp and UHMWPE tray were carried out using SEM. Shape of UHMWPE tray was determined three-dimensionally. Comparing the result with original shape based on the product’s plan, liner wear and volumetric wear were calculated. Oxidation index was determined by Fourier transform infrared spectrophotometry. Alumina F-Comp did not have any scratch on the surface by seeing with naked eye. UHMWPE tray had deformation and scratches obviously. The liner wear rate was 37 micrometer/year and volumetric wear rate was 18.8 mm3/year. The oxidation indexes were 0.6 in the unworn area, 1.2 in the worn area and 0.2 in the inner area. SEM observations of the F-Comp demonstrated no scratch or pit. In contrast, many scratches were clearly observed on the UHMWPE tray. However, higher magnification observations did not demonstrate severe wear, which was shown on the wear analysis of a metallic F-Comp. Oxidation degradation is a problem to solve. However, the low wear rate and mild wear pattern demonstrate that ceramic F-Comp reduced UHMWPE wear.