Abstract

Using a femoral head from one manufacturer on the stem of another manufacturer poses the risk that the taper interface between the components do not contact correctly and the performance of the joint will be impaired. The cohorts in this study are a combination of modular Birmingham Hip Resurfacing (BHR) and Adept femoral heads on CPT stems. The study reviews the geometry of the taper interfaces to establish if the taper clearance angles was outside of the normal range for other taper interfaces. In addition the rates of material loss from the bearings and taper and a ranking of the stem damage were reviewed to determine if the levels of loss were above that seen for other similar joints.

The material loss analysis demonstrated that the rates or levels of loss from the bearings, taper and stem are no different to levels published for manufacturer matched joints and in many cases are lower. The results demonstrate that the taper clearance angles for the mixed manufacturer joints (BHR-CPT: 0.067 to −0.116, Adept-CPT: 0.101 to −0.056) were within the range of other studies and manufacturer matched clearances (0.134 to −0.149).

Using components from different manufacturers has not in this instance increased the level of material loss from the joints, when compared to other similar manufacturer matched joints.

Aims

This retrospective study aimed to determine the causes of in-hospital death after Neck of Femur (NOF) fracture in Southampton General Hospital (SGH) over a 6 year period, comparing the clinical cause of death with findings at post-mortem. A previous study showed discrepancies between pre-mortem clinical diagnosis and autopsy findings after in-hospital deaths in SGH.

Pseudotumour formation is being reported with increasing frequency in failing metal-on-metal hip resurfacings and replacements. This mode of failure complication has also been reported with metal-on-polyethylene bearing bearings when it is usually associated with evidence of surface corrosion and no apparent wear at the head–neck taper.

We present a case with evidence of taper wear and damage secondary to corrosion in an uncemented total hip replacement with a metal on polyethylene articulation (TMZF (Titanium, Molybdenum, Zirconium and Ferrous) Accolade® stem, Trident® HA coated acetabular shell, Low Friction Ion Treatment (LFIT™) Cobalt-Chrome anatomic head (40 mm), X3® polyethylene liner)

Aim

Alumina ceramic on ceramic bearings in total hip arthroplasty (THA) may reduce the prevalence of osteolysis due to its properties of low wear and chemical inertness. This is critical in the younger patient population as they place increased demands over a longer period. This study reports on the clinical and radiographic outcomes of a series of modern cementless ceramic on ceramic THA at a minimum of 10 years in this younger group.

Introduction

Controversy exists as to whether the short external rotator tendons and capsule of the hip should be repaired after posterior approach primary total hip arthroplasty (THA). Recent studies using radiopaque markers have demonstrated that reimplantation of these muscle tendons fail early and may not prevent post operative dislocation.

Introduction

Traditional TKR designs exhibit abnormal and unpredictable kinematics: with posterior subluxation in extension and anterior slide with flexion. These can contribute to restricted knee flexion and reduced quadriceps efficiency. Newer designs attempt to provide “guided motion” with the aim of mimicking normal knee kinematics. The Journey (Smith & Nephew) BCS TKR incorporates both an anterior and a posterior cam/post mechanism while Triathlon PS TKR (Stryker) incorporates a posterior cam/post mechanism. This study compares the in-vivo kinematics of these two designs and compares it with normal knee.

OBJECTIVE

To examine the short term patient assessed functional results of the Journey BCS ¯(Smith & Nephew) and Triathlon ¯(Stryker Orthopaedics, Mahwah, NJ) total knee replacements when compared to the Scorpio ¯(Stryker) total knee replacement using a multi-surgeon case control design in a single centre.

Background: The use of fresh morsellised allograft in impaction bone grafting for revision hip surgery remains the gold standard. Bone marrow contains osteogenic progenitor cells that arise from multipotent mesenchymal stem cells and we propose that in combination with allograft will produce a living composite with biological and mechanical potential. This study aimed to determine if human bone marrow stromal cells (HBMSC) seeded onto highly washed morsellised allograft could survive the impaction process, differentiate and proliferate along the osteogenic lineage and confer biomechanical advantage in comparison to impacted allograft alone

Methods: HBMSC were isolated and culture expanded in vitro under osteogenic conditions. Cells were seeded onto prepared morsellised allograft and impacted with a force equivalent to a standard femoral impaction (474J/m2). Samples were incubated for either two or four week periods under osteogenic conditions and analysed for cell viability, histology, immunohistochemistry, and biochemical analysis of cell number and osteogenic enzyme activity. Mechanical shear testing, using a Cam shear tester was performed, under three physiological compressive stresses (50N, 150N, 250N) from which the shear strength, internal friction angle and particle interlocking values were derived.

Results: Cell viability of HBMSC post impaction, was confirmed with cell tracker green staining, a marker of viable cells, and observed throughout all samples. There was a significant increase in DNA content and specific alkaline phosphatase activity compared to impacted seeded allograft samples. Immunohistochemical staining for type I collagen confirmed cell differentiation along the osteogenic lineage. Mechanical shear testing demonstrated a statistical significant increase in shear strength and interparticulate cohesion in the allograft/hBMSC group over allograft alone at 2 and 4 week intervals (p< 0.001).

Conclusion: HBMSC seeded onto allograft resulted in the formation of a living composite capable of withstanding the forces equivalent to a standard femoral impaction. HBMSC under osteogenic conditions were observed to differentiate and proliferate along the osteogenic lineage. In addition, an allograft/HBMSC living composite confers a biomechanical advantage over allograft alone These changes resulting in enhancement of biological and mechanical properties of bone graft within impaction bone grafting have implications for translation and future change in orthopaedic practice in an increasing ageing population.

Introduction: Bone is unique with a vast potential for regeneration from cells with stem cell characteristics. With an increasing aging population, clinical imperatives to augment and facilitate tissue repair have highlighted the therapeutic potential of harnessing mes-enchymal populations from bone. We describe laboratory and clinical findings from two clinical cases, where different proximal femoral conditions (AVN, bone cyst) were treated with impacted allograft augmented with marrow-derived allogeneic progenitor cells.

Methods: Marrow was aspirated from the posterior superior iliac crest and seeded onto prepared washed morsellised allograft. The seeded graft was left for 40 minutes to allow adherence of the marrow-derived osteoprogenitor cells prior to impaction into the defect. Samples of the impacted graft were taken for in-vitro analysis of cell viability, histology and biochemical analysis of cell number and osteogenic enzyme activity. The total force imparted during impaction was calculated using a load cell, with three independent surgeons performing a laboratory simulation of the impaction technique.

Results: Both patients made a rapid clinical recovery after an overnight stay. Imaging confirmed filling of the defects with increased density on plain radiographs suggesting good impaction of the graft composite. Immu-nohistochemical staining of graft samples demonstrated that a living composite graft with osteogenic activity had been introduced into the defects as evidenced by cell tracker green viability and alkaline phosphatase (osteogenic marker) expression and specific activity. The average peak forces during impaction were 0.7kN corresponding to average peak stresses within the graft of 8.3MPa. Similar forces were seen between operators.

Discussion: Replacement of bone loss remains a major challenge in orthopaedic practice. Although allograft remains the gold standard where large volumes preclude autograft, allograft has little osteoinductive potential. We demonstrate that marrow-derived cells can adhere to highly washed morsellised allograft, survive the impaction process, and are of the osteoblastic phenotype creating a living composite. Thus we conclude, impacted allograft seeded with autologous marrow cells allows the delivery of a biologically active scaffold for the treatment of bone deficiency. In addition this is a novel straightforward technique, surgeon independent and with applications in a number of orthopaedic scenarios.

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.

Results. Less than 5% of the chondrocytes in superficial layer from #NOF cartilage expressed degradative enzymes, whereas all cloned chondrocytes from advanced-stage OA cartilage were immunopositive. The overall % of CpG demethylation in the promoters of control patients (whose chondrocytes did not express the enzymes) was 20.1%, whereas 48.6% of CpG sites were demethylated in degradative chondrocytes of OA patients (p< 0.001). For MMP-13, the increase in demethylation between control and OA was from 4 ^..20%; for MMP-9 from 47 ^..81% and for MMP-3 from 30 ^..57%. However, not all available CpG sites were equally demethylated. Some sites were uniformly methylated in both OA and controls, others were demethylated even in controls. However, there was at least one crucial site for each degradative enzyme, where the differences in the degree of methylation were greatest and statistically different. These sites were at −110 for MMP-13; −36 for MMP-9; −635 for MMP-3. There was no relation between the % demethylation and the patient fs age and no apparent difference between males and females.

Conclusions: We have demonstrated an association between abnormal gene expression of MMP-3, MMP-9 and MMP-13 and promoter DNA demethylation. This epigenetic dysregulation of genes appeared to be clonally inherited by daughter cells and may be typical for osteoarthritis and other complex, late-onset diseases.

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

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.

The demographic challenges of an advancing aged population emphasise the need for innovative approaches to tissue reconstruction to augment and repair tissue lost as a consequence of trauma or degeneration. Currently, the demand for bone graft outstrips supply, a key issue in the field of revision hip surgery where impaction bone grafting of the femur and acetabulum has impressive results in the short and medium term but often requires up to 6 donated femoral heads. Spine and selected tumour and trauma cases are also eminently suitable for this mode of bone stock replacement. In the current study, we examined the histological and biochemical findings of two parallel in-vitro and in-vivo studies using human mesenchymal stem cells on synthetic scaffolds for possible bone augmentation. The first study confirmed that culture expanded bone marrow cells from 3 patients (mean age 76 +/−4) could be successfully seeded onto washed morsellised allograft. The seeded graft was then exposed to a force equivalent to a standard femoral impaction (impulse=474 J/m2) and cultured for 4 weeks in osteogenic media. Examination of cell viability using cell tracker green and ethidium homodimer-1 and confocal microscopy confirmed extensive cell proliferation and viability following impaction and culture. Alcian blue/ Sirius red confirmed matrix production, alkaline phosphatase immunocytochemistry production of enzyme activity and Goldners trichrome enhanced osteoid formation. The second study compared 3 scaffolds; bone allograft, a ß – Tricalcium Phosphate (ß-TCP) graft substitute and a 50:50 mixture of allograft and ß-TCP. The scaffolds were seeded with either immunoselected STRO-1+ human mesenchymal stem cells or unselected marrow cells. The scaffolds were similarly exposed to impaction forces and cultured for 4 weeks in vitro or in vivo, implanted subcutaneously in MF1nu/nu mice. Both studies demonstrated cellular viability, activity and osteogenesis as assessed using confocal microscopy, Goldners trichrome and alcian blue/Sirius cytochemistry. The demonstration of enhanced osteoid formation as a consequence of stem cell proliferation after impaction grafting augers well for the success of autologous stem cell implantation on impacted graft substitute with or without the addition of morsellised allograft. The implications therein for clinical use in the future await clinical trials.

Introduction and Aims: Retrospective analysis of 25 consecutive metal-on-metal proximal femoral replacements performed at our unit between 1965 and 1979.

Method: Patients were clinically evaluated using the Modified Harris hip and Enneking Scoring Systems and radiologically evaluated using the ISOLOS scoring system. The concentration of Cr, Co, Ti, Al, V, Mo & Ni in whole blood and urine was also measured by High-Resolution Inductively Coupled Mass Spectrometry and compared with controls and patients with other implants.

Retrieved prostheses (in-situ for in excess of 25 years) were analysed for roughness and wear using a Mitutoya form tracer and an electron microscope.

Results: Thirteen patients have since died, nine from metastatic disease and four from other causes. Of the remainder, 11 (44%) are still alive, five still retaining metal-on-metal articulations and one has been lost to follow-up. They have been in-situ for an average of 32 years. The average modified Harris hip score is 76 (53–93) and the average Enneking Score is 74 (63–90).

In the retrieved prostheses the contact zones were found to be smoother (Ra 0.05mm), have fewer and smaller carbides, together with evidence of ‘self-healing’ when compared to the original surface (Ra 0.32mm).

Blood and urine levels of Co & Cr were significantly elevated. Co levels were exceptionally elevated in loose prostheses, but levels quickly fell following revision.

Conclusion: We have shown the potential longevity of metal-on-metal arthroplasty. The wear seen in retrieved specimens is low and we might expect to improve the fixation by reducing the torque with apical bearing and encouraging extra-cortical bone bridging with hydroxy-apatite-coated collars. Elevated serum and urine Co levels may well predict a loose prosthesis and may be useful as a screening tool.

Retrospective analysis of 25 consecutive metal on metal proximal femoral replacements performed at our unit between 1965 and 1979.

Methods. Patients were: clinically evaluated using the Modified Harris Hip and Enneking Scoring Systems and radiologically using the ISOLOS scoring system.

The concentration of Cr, Co, Ti, Al, V, Mo & Ni in whole blood and urine was also measured by High-Resolution Inductively Coupled Mass Spectrometry and compared with controls and patients with other implants.

Retrieved prostheses (in situ for in excess of 25 years) were analysed for roughness and wear using a Mitutoya form tracer and an electron microscope.

Results. Thirteen patients have since died; nine from metastatic disease and four from other causes. Of the remainder, eleven (44%) are still alive, five still retaining metal on metal articulations and one has been lost to follow up. They have been in situ for an average of 32 years. The average modified Harris Hip score is 76 (53–93) and the average Enneking Score is 74 (63–90).

In the retrieved prostheses the contact zones were found to be smoother (Ra 0.05?m), have fewer and smaller carbides together with evidence of ‘self-healing’ when compared to the original surface (Ra 0.32?m).

Blood & urine levels of Co & Cr were significantly elevated. Co levels were exceptionally elevated in loose prostheses but levels quickly fell following revision.

Conclusion. We have shown the potential longevity of metal on metal arthroplasty. The wear seen in retrieved specimens is low and we might expect to improve the fixation by reducing the torque with apical bearing and encouraging extra-cortical bone bridging with hydroxy-apatite coated collars. Elevated serum and urine Co levels may well predict a loose prosthesis and may be useful as a screening tool.