Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

To propose a modified approach to measuring femoro-epiphyseal acetabular roof (FEAR) index while still abiding by its definition and biomechanical basis, and to compare the reliabilities of the two methods. To propose a classification for medial sourcil edges.

We retrospectively reviewed a consecutive series of patients treated with periacetabular osteotomy and/or hip arthroscopy. A modified FEAR index was defined. Lateral center-edge angle, Sharp's angle, Tonnis angle on all hips, as well as FEAR index with original and modified approaches were measured. Intra- and inter-observer reliability were calculated as intraclass correlation coefficients (ICC) for FEAR index with both approaches and other alignments. A classification was proposed to categorize medial sourcil edges. ICC for the two approaches across different sourcil groups were also calculated.

After reviewing 411 patients, 49 were finally included. Thirty-two patients (40 hips) were identified as having borderline dysplasia defined by an LCEA of 18 to 25 degrees. Intra-observer ICC for the modified method were good to excellent for borderline hips; poor to excellent for DDH; moderate to excellent for normal hips. As for inter-observer reliability, modified approach outperformed original approach with moderate to good inter-observer reliability (DDH group, ICC=0.636; borderline dysplasia group, ICC=0.813; normal hip group, ICC=0.704). The medial sourcils were classified to 3 groups upon its morphology. Type II(39.0%) and III(43.9%) sourcils were the dominant patterns. The sourcil classification had substantial intra-observer agreement (observer 4, kappa=0.68; observer 1, kappa=0.799) and moderate inter-observer agreement (kappa=0.465). Modified approach to FEAR index possessed greater inter-observer reliability in all medial sourcil patterns.

The modified FEAR index has better intra- and inter-observer reliability compared with the original approach. Type II and III sourcils accounts for the majority to which only the modified approach is applicable.

Aims

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

Aims

The rate of dislocation when traditional single bearing implants are used in revision total hip arthroplasty (THA) has been reported to be between 8% and 10%. The use of dual mobility bearings can reduce this risk to between 0.5% and 2%. Dual mobility bearings are more expensive, and it is not clear if the additional clinical benefits constitute value for money for the payers. We aimed to estimate the cost-effectiveness of dual mobility compared with single bearings for patients undergoing revision THA.

The purpose of this investigation is to assess the rate of wear the effect once the “bedding in period”/ poly creep had been eliminated. Creep is the visco-elastic deformation that polyethylene exhibits in the first 6–12 weeks. We also assessed the wear pattern of four different bearing couples in total hip arthroplasty (THA): cobalt-chrome (CoCr) versus oxidized zirconium (OxZir) femoral heads with ultra-high molecular weight polyethylene (UHMWPE) versus highly-crosslinked polyethylene (XLPE) acetabular liners.

This was a randomized control study involving 92 patients undergoing THA. They were randomized to one of four bearing couples: (1) CoCr/UHMWPE (n= 23), (2) OxZir/UHMWPE (n=21), (3) CoCr/XLPE (n=24), (4) OxZir/XLPE (n=24). Patients underwent a posterior approach from one of three surgeons involved in the study. All patients received a porous-coated cementless acetabular shell and a cylindrical proximally coated stem with 28 mm femoral heads. Each patient was reviewed clinically and radiographically at six weeks, three and 12 months, two, five and 10 years after surgery. Standardized anteroposterior and lateral radiographs were taken. All polyethylene wear was measured by an independent blinded reviewer. Linear and volumetric wear rates were measured on radiographs using a validated computer software (Polyware Rev. 5). Creep was defined as the wear at 6 or 12 weeks, depending on if there was a more than 10% difference between both measurements. If a greater than 10% difference occurred than the later period's wear would be defined as creep.

72 hips were included in analysis after exclusion of seven revisions, three deaths and 10 losses to follow-up. The annual linear wear rates (in mm/y) at 10 years were (1) 0.249, (2) 0.250, (3) 0.074 and (4) 0.050. After adjusting for creep these rates become were (1) 0.181, (2) 0.142, (3) 0.040 and (4) 0.023. There is statistical differences between raw and adjusted linear wear rates for all bearing couples. The percentage of the radiographically measured wear at 10 years due to creep is (1) 30% (2) 44%, (3) 58.5% and (4) 51.5% with significant differences in couples with XLPE versus those with UHMWPE. There was no significant correlation between age, gender, cup size, tilt, planar anteversion and the linear or volumetric wear rates.

The linear wear rate of both UHMWPE and XLPE are even lower thxdsxzan previously described when creep is factored out. XLPE has again demonstrated far superior linear wear rates at 10 years than UHMWPE. There were no significant differences in wear rate at 10 years between CoCr and OxZir, this may be due to an underpowered study. XLPE exhibits proportionally more creep than UHMWPE within the first 6–12 weeks and accounts for more of the total wear at 10 years as measured radiographically at the end period.

High resolution imaging techniques such as atomic force microscopy, provide a platform to study the fibrillary architecture of biological tissues, but are not capable of imaging the internal microstructure of tissues in 3D. Conversely, multiphoton microscopes facilitate 3D imaging to study the spatial relationship of micro-components within tissues, but without the resolution of atomic force microscopy. The lamina splendens is the most superficial layer of articular cartilage. It is believed to play a crucial role in the health of the tissue. However, the precise form of this layer is uncertain as it has never been independently studied. Here, we use multiphoton microscopy and atomic force microscopy to demonstrate the anatomic form of the lamina splendens. The lamina splendens were peeled from the femoral condyles of healthy, adult sheep (n=20). Using atomic force microscopy, we show that the collagen and elastin form an interweaving fibrillary network at the surface of the lamina splendens and at the interface of the lamina splendens with the underlying cartilage. Moreover, using fluorescent stains; sulforhodamine B and acridine orange, multiphoton microscopy shows the heterogeneous distribution of collagen, elastin and chondrocytes throughout the depth of the lamina splendens. Our results demonstrate the fibrillary and component level architecture of the lamina splendens. We believe our findings provide the backbone of knowledge to advance tissue engineering techniques that will lead to more promising strategies to treat cartilage pathologies, including osteoarthritis. Furthermore, our results provide a starting point to determine the role of the lamina splendens in cartilage pathology.

The health of a synovial joint is relied on normal function and coordination of a group of tissues such as articular cartilage (AC), ligaments, tendons and muscles. Osteoarthritis (OA), which is the most common joint disease, is clinically characterised by lesion of AC. Despite this, injury of a ligament or tendon or muscle generates a joint instability, which accelerates deterioration of AC and progression of OA. Traditional histology is often used to study the pathology of biological tissues. It requires tissue biopsy, which traumatises the donor tissues. Therefore, it is not an idea method for assessing AC, ligaments and tendons as the tissues have a poor healing capability. There is a worldwide demand of an imaging technique that diagnoses the microstructural changes of chondral and connective tissues without biopsy. Confocal arthroscopy (Optiscan Pty Ltd, Australia) possesses a Ø 6.3 mm probe and offers a 0.7 µm lateral imaging resolution and 7 µm axial resolution. It has been successfully used for examining the internal microstructural disorders in rotator cuff tendons of human cadavers without tissue biopsy (WU et al., 2015). This study investigates the capability of confocal arthroscopy as optical histology for assessing the internal microstructure of AC, ligaments, tendons and muscles in a knee joint.

Four sheep keen joints were freshly donated by other research unrelated to this study. After 5 ml clinical grade fluorescein solution at 0.05 g/L was injected into the joint cavity of a knee joint, the joint was passively exercising for about 10 minutes. The joint was then open collaterally and washed thoroughly using PBS for acquiring the microstructure of AC, ligaments, tendons and muscles using the confocal arthroscopy.

Results: without biopsy, confocal arthroscopy offers an imaging resolution for onsite distinguishing the subtle microstructural difference of AC in the weight-bearing and non-weight bearing region. It also permitted visualising the hierarchical collagen structure in ligaments and tendons at a fibre level, and characterising the muscle nuclei, motor-neurons, moto-neuron synapse and striates of myofibres.

Confocal arthroscopy showed the early promise to act as optical histology for studying the microstructure of chondral and a range of connective tissues, which allows understand better the health status of a knee joint. Since a sheep knee joint is very small for operating a normal procedure of an arthroscopic examination, an open knee joint surgery was performed in this study to allow imaging the microstructure of AC and a range of connective tissues. This is accounted as a limitation in the study. Nevertheless, this study demonstrated the development of confocal arthroscopy may lead to optical histology of the internal microstructure of AC and a group of connective tissues, which offers understanding more comprehensively the healthy status of a knee joint.

A tendon is a fibrous connective tissue that acts to transmit tensile forces between muscles and bones. It mainly consists of soluble substance, collagen and small volume of elastic fibres, which are produced by tenoblasts and tenocytes. The Achilles tendon is the thickest tendon in the human body that subjects to some of the highest tensile force, thus disorders and ruptures commonly happen. As the insoluble fibrous components in Achilles tendons, the collagen fibrils and elastic fibres have unique spatial structure that plays important functional roles. Despite this, the understanding of relationship between them is still limited due to the lack of imaging evidence. Using confocal and second harmonic generation microscopy, this study aims to comprehensively investigate the spatial relationship of collagen, elastic fibres and tenocytes in hydrated tendons.

Longitudinal sections of 50 µm thick and transverse sections of 20 µm thick were cryo-sectioned respectively from the mid-portion of ten rabbit Achilles tendons. Sections were stained with 0.03g/L Acridine Orange (AO) and 1mg/ml Sulforhodamine B (SRB) solution respectively for labelling the nucleus and elastic fibres. The Leica TCS SP2 multiphoton microscopy containing second harmonic generation microscopy can image collagen without labelling. The sections were scanned by the multiphoton microscopy, and images were processed and reconstructed into 3D images to study the spatial structure of collagen, elastic fibres and cells in Achilles tendons

A rabbit Achilles tendon consists of three sub-tendons named flexor digitorum superficialis tendon, medial gastrocnemius tendon and lateral gastrocnemius tendon. Loose connective tissue connects the three sub-tendons and ensures efficient sliding between sub-tendons. The 3D network shows that the mid-portion of Achilles tendons is composed of longitudinal collagen and elastic fibres, while spindle tenocytes rest along the collagen and elastic fibres. Tenocytes appear to have a closer microstructural relationship with the elastic fibres. In comparison with the collagen, tenocytes and elastic fibres only occupy a very small volume in the 3D network. The elastic fibres exist in both tendon proper and endotenons. The tendon sheath and loose connective tissue have a higher cell density, and the cells are large and round while compared with tenocytes.

As a component of the extracellular matrix (ECM) in Achilles tendons that closely mediates with the tenocytes, the elastin may participate in the force transition and interaction between tenocytes and the ECM. The elastic fibres may also endow Achilles tendons with unique mechanical properties to stand for tensile force.

Objectives

To employ a simple and fast method to evaluate those patients with neurological deficits and misplaced screws in relatively safe lumbosacral spine, and to determine if it is necessary to undertake revision surgery.

During a retrospective case note analysis, a significant difference was found in prosthesis survival, between two cohorts of patients who underwent different total knee replacements. The first cohort included 70 patients who underwent Kinemax Plus total knee replacement, the second cohort included 58 patients who underwent PFC Total Knee replacement. All patients were under the care of one Consultant Orthopaedic Surgeon. Interestingly, the Kinemax Plus cohort was found to have a higher rate of revision compared to the PFC cohort. A detailed comparison was carried out between the two groups to identify any obvious cause for the disparity.

The two cohorts were found to be well matched with respect to age, sex, ASA grade, underlying pathology and operative technique. Median follow up being 6 years and 5 years for the Kinemax Plus and PFC groups respectively.

There were 11 failed prostheses in the Kinemax Plus cohort, 7 undergoing revision with the remaining 4 patients offered revision but unwilling to have surgery. Wear of the polyethylene tibial insert was the most obvious finding at revision, present in six of the seven revisions. 97% of the Kinemax Plus Prostheses were intact at 5 years but by 8 years only 87% were intact. There were no revisions performed in the PFC cohort.

Post-operative x-ray analysis was undertaken to rule out prosthesis malalignment as a cause for the increased failure rate. The coronal alignment of the prostheses (CAK) was calculated and all post operative x-rays were within the normal limits of 4-10 degrees.

Analysis of the explanted Kinemax Plus polyethylene liners was undertaken. In six cases, the polyethylene bearing surfaces displayed severe surface and subsurface delamination. This suggests massive fatigue and fatigue wear. Only one implant showed localised delamination.

These findings suggest the hypothesis of weak polyethylene particle interface strength.

Orthopaedic grade ultra-high molecular weight polyethylene (UHMWPE) remains the preferred material for one of the bearing surfaces in total joint prostheses because of its high wear resistance and proven biocompatibility. Since the 1970s, UHMWPE has served as the only widely used bearing material for articulation with metallic components in total knee arthroplasty (TKA). However, polyethylene-related total knee failures have limited the lifetime of total knee joint replacements. The present study is focused on improving material integrity and reducing the probability of material failure. The hypothesis examined here is that there is a correlation between material failure of UHMWPE knee-joint components and the precise time-temperature history employed during fabrication, due to their strong effect on interparticle cohesion. The presence of fusion defects due to incomplete consolidation and incomplete polymer self-diffusion has been implicated in the failure of UHMWPE joints [1, 2]. Computer-aided methodology used in this study allowed quantitative prediction and optimisation of the extent of interparticle cohesion to ensure that inter-particle boundaries are of high integrity during moulding [3]. The current study has investigated the correlation between inter-particle cohesion governed by reputation theory and wear performance.

We have investigated the wear performance of direct compression moulded UHMWPE plates with different degree of inter-particle diffusion. Direct compression moulding was used in the present study because of its uniformly excellent surface finish which is better than machined surfaces. UHMWPE plates (44×24×3mm) were direct compression moulded using GUR1050 powder (Ticona). Various moulding temperature (e.g. 145°C, 150°C, 175°C) and dwell time (e.g. 15mins and 30mins) were investigated.

The wear tests were carried out at 37°C using a Durham four-station multidirectional pin-onplate machine, which generates both reciprocating and rotating motions simultaneously. The material combination of the flat-ended metallic indentors loaded against UHMWPE plates was constructed to mimic conformal contact conditions in knee prostheses. The articulating surfaces were lubricated using 25% diluted bovine serum. Meanwhile the experimental method was validated by evaluating the wear generation under the conventional configuration (i.e. UHMWPE pins on metal plates); results were comparable with the data in the literature [4].

For the direct compression moulded UHMWPE plates, experimental wear factors were determined and found to correlate well with numerically calculated degree of inter-particle diffusion. Increasing moulding temperature and dwell time decreased the wear factors and increased inter-particle diffusion. Surface structures were characterised before and after every 0.5 million cycles. The observed surface features on UHMWPE plates in ESEM and optical microscopy is very similar to those in retrieved knee prostheses [5] and those found in our own recent work with knee wear simulator testing.

The Kinemax Plus knee replacement has a reported 10 year survival of around 96%. However we found the survival rate of this implant in our cohort to be 75% at 9 years. No abnormalities were found for clinical and radiological parameters. At reoperation the most striking feature was that of significant ultra-high molecular weight polyethylene (UHMWPE) failure. Oxidative and structural analysis of the polyethylene components was therefore undertaken.

Ten Kinemax Plus tibial inserts were analysed; one was a shelf-aged unused implant, the others were explants. An FTIR analysis of the data showed that oxidation is present in all samples. The degree of oxidation however varied with depth and location. Except for a sharp oxidative peak approximately half way into the sample, the shelf aged samples had a fairly constant level of oxidation. The retrieved implants had an overall higher level of oxidation in both bearing and non-bearing regions. The latter had less of a variation in oxidation which implies that in vivo loading exaggerates the degree of oxidation. In the non-articulating regions oxidation of the explants was found to peak often at the region of about 40% from the bottom surface in all retrieved samples. By contrast, most articulating region had two oxidative peaks; one occurring at approximately 1–1.5mm from the surface, which is consistent with findings on subsurface oxidation, and another occurring about 2–3mm from the bottom surface.

SEM imaging provided evidence for the presence of fusion defects by indicating grain boundaries through-out the explants. This indicates a compromised material which is more susceptible to damage. Fatigue loading of the implant has also been seen to produce a subsurface stress maximum at approximately 1 to 2mm below the articulating surface. It is thought that maximum contact stresses within this region cause Type 1 and Type 2 defects to open or become more pronounced. This in turn will increase the local concentration of oxygenating material as it will be present in these defects and voids where surface areas are greater for oxidative reaction. We therefore hypothesise that these fusion defects are the cause for the early failure of the Kinemax implants.

We aim to explain the significant difference in survivor-ship found between two cohorts of patients who underwent different total knee replacements. The first cohort included 70 patients who underwent Kinemax Plus total knee replacement, the second cohort included 58 patients who underwent PFC Total Knee replacement. All patients were under the care of one Consultant Orthopaedic Surgeon.

Interestingly, the Kinemax Plus cohort was found to have a higher rate of revision as compared to the PFC cohort. A detailed comparison was then carried out between the two groups to identify any obvious cause for the disparity.

The two cohorts were found to be well matched with respect to age, sex, ASA grade, underlying pathology and operative technique. Median follow up being 6 years and 5 years for the Kinemax and PFC groups respectively. There were 11 failed prostheses in the kinemax cohort, 7 undergoing revision with the remaining 4 patients offered revision but unwilling have surgery. Wear of the polyethylene tibial insert was the most obvious finding at revision, present in six out of the 7 revisions. 97% of the Kinemax Plus Prostheses were intact at 5 years but by 8 years only 87% were intact.

There were no revisions performed in the PFC cohort.

Post operative x-ray analysis was undertaken to rule out prosthesis misalignment as a cause for the increased failure rate. The coronal alignment of the prostheses (CAK) was calculated and all post operative x-rays were within the normal limits of 4–10 degrees.

Analysis of the explanted Kinemax Plus polyethylene liners was undertaken. In six cases, the polyethylene bearing surfaces displayed severe surface and subsurface delamination at both medial and lateral sides. This suggests massive fatigue and fatigue wear. Only one inplant showed localised delamination. The surface characterisation suggests the hypothesis of weak UHMWPE particle interface strength.

Aseptic loosening caused by UHMWPE wear debris induced osteolysis is a major cause of revision in total hip arthroplasty (THA)¹. While second generation hard-on-hard bearings, metal-on-metal (MOM) and ceramic-on-ceramic (COC), have been shown clinically to address the wear issues associated with conventional UHMWPE bearings, there remain some concerns over the potential effects of metal ions produced by MOM and the risk of liner fracture in COC. Recently, hybrid ceramic-on-metal (COM) articulation has received a great deal of attention as a promising alternative bearing.

Advantages include reduced wear and metal ion release compared with MOM. In addition, it is thought that there may be a reduced tendency for fracture of the ceramic component due to the softer metallic cup.

In this study a 5 million cycle wear test was carried out on the Mark II Durham Hip Wear Simulator. A set of six, 38mm diameter HIPed alumina heads and as-cast CoCr alloy cups were tested in bovine serum. Surface topography analysis was carried out at 0, 2, 3 and 5 million cycles. Additionally imaging of the bearing surfaces using ESEM and AFM was undertaken on the final bearing surface. Friction testing, using the Durham Hip Friction Simulator was carried out on one of the joints worn to 5 million cycles and the results were compared with theoretical calculations.

Wear of the ceramic heads was virtually undetectable using the conventional gravimetric methods. However, minor surface damage in the form of grain pull out and abrasive scratches was observed in the wear patch when the bearing surfaces were analysed using ESEM and AFM. The grains were not visible in the unworn sections of the head. The average surface roughness remained constant throughout the test. The CoCr cups showed a decrease in roughness between 0 and 2 million cycles, after which it remained relatively constant. This was consistent with the wear results in which a biphasic wear rate was found. The more frequently obtained wear results showed running in wear rate of 1.02±0.078 mm3/million cycles between 0–0.5 million cycles, followed by a steady state wear rate of 0.030±0.011 mm3/million cycles. These results are consistent with those of a recent study undertaken elsewhere².

Friction testing produced a Stribeck curve which was indicative of full fluid film lubrication with a friction factor of 0.027±0.002 for 25% bovine serum (η=0.0014 Pa s-1). Other tests were also carried out using carboxy methyl cellulose fluid as the lubricant to investigate the effect of proteins. This showed that there was a small decrease in friction factor when proteins were absent from the lubricant. It is thought that the difference in friction factors is due to adsorption of the proteins onto the bearing surfaces, when lubricated in bovine serum. This introduces large proteins between the bearing surfaces, which penetrate the lubricant film, causing protein on protein interactions, in addition to the friction caused by shearing of the lubricant film.

We describe a cohort of patients with a high rate of mid-term failure following Kinemax Plus total knee replacement inserted between 1998 and 2001. This implant has been recorded as having a survival rate of 96% at ten years. However, in our series the survival rate was 75% at nine years. This was also significantly lower than that of subsequent consecutive series of PFC Sigma knee replacements performed by the same surgeon. No differences were found in the clinical and radiological parameters between the two groups. At revision the most striking finding was polyethylene wear. An independent analysis of the polyethylene components was therefore undertaken. Scanning electron microscopy revealed type 2 fusion defects in the ultra-high molecular weight polyethylene (UHMWPE), which indicated incomplete boundary fusion. Other abnormalities consistent with weak UHMWPE particle interface strength were present in both the explanted inserts and in unused inserts from the same period.

We consider that these type 2 fusion defects are the cause of the early failure of the Kinemax implants. This may represent a manufacturing defect resulting in a form of programmed polyethylene failure.

Intoduction: There is a general consensus with regard to the treatment of extacapsular fractures of the hip, however the surgical treatment and the choice of implant in displaced intracapsular fractures remains controversial. Evidence has not definitively established the relative merits of the optimal device for internal fixation. The management of displaced intracapsular femoral neck fractures depends on surgeon’s preference.

Methods: We have done a study using synbone (Corticocancellous with similar properties of natural bone) comparing three methods of fixation (three parallel cannulated screws, two hole dynamic hip screw with and without a derotation screw, four constructs of each fixation). We looked at the ultimate peak loads that a construct can withstand before failure.

Results: There is a significant difference between the cannulated screws and two hole Dynamic hip screw, the latter being stronger of the two. However there is no biomechanical advantage of using the derotation screw.

Discussion: Although this study provides evidence of superiority of dynamic hip screw over cannulated screws, this is limited to the biomechanical properties of the construct. The ultimate clinical failure can depend on numerous other factors. Based on our study we recommend two-holed Dynamic Hip Screw fixation for displaced intracapsular fractures of proximal femur.

Introduction and Aims: Autologous chondrocyte implantation (ACI) is emerging as a leading technique for the treatment of articular cartilage defects. However, there exists some debate regarding which ACI technique is best able to regenerate hyaline cartilage. To this end, the development of a non-invasive technique enabling the examination of microstructure after ACI is essential.

Method: In this study, we have developed a novel 2D Laser Scanning Confocal Arthroscope (LSCA) in the assessment of articular cartilage and examined the microstructure of knee articular cartilage from rabbits and patients with total knee arthroplasty. The LSCA system consists of the LSA handheld probe, a Launch and Detection Unit (LDU) with a built in 488nm–514nm Krypton Argon Laser and Master Control unit (MCU). Human and rabbit knee articular cartilage stained with Fluoroscein (5g/L) and Acriflavine (0.5g/L) were used to examine the microstructure of cartilage by LSCA.

Results: By LSCA we have generated optical histology images of normal human and rabbit articular cartilage from the femoral condyle. Optical histology of normal articular cartilage tissue reveals typically smooth surface texture with relatively homogenous sub-surface distribution of viable chondrocyte cells. The general orientation of collagen fibres is occasionally visible in surface images. Optical histology of arthritic cartilage of humans showed clusters of round-shaped chondrocytes mixed with spindle-shaped cells. Surface cracking typically indicative of tissue damage is also evident by LSCA observation. Examination of rabbit knee six weeks after ACI showed high density of chondrocytes and homogeneous matrix on the site of the defect.

Conclusion: In short, we have shown the efficacy of LSCA in the non-destructive assessment of articular cartilage in vivo. Further study is required to evaluate the clinical significance of optical histology of LSCA.

Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein’s triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95).

Our findings indicate that tryptophan polymorphisms predispose carriers to the development of symptomatic spinal stenosis associated with spondylolisthesis which requires surgery.