Aims

A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients’ quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures.

Introduction

The National Joint Registry of England, Wales, Northern Ireland, and the Isle of Man (NJR) monitors the performance of primary total hip arthroplasty (THA) implants and summarizes usage and outcomes for specific hip systems. The objectives of this study were to 1) determine if survivorship for the PROCOTYL® L acetabular cup, a hemispherical press-fit cup coated with hydroxyapatite and a metal on XLPE articulation, is significantly different from all other cementless cups in the NJR and 2) to analyze patient reported outcomes measures (PROMs) at a minimum five year follow-up for the subject cup.

Objectives

Total hip replacement is increasingly being conducted in younger and more active patients, so surgeons often use bearing surfaces with improved wear characteristics, such as ceramic on ceramic. The primary objective of this study was to determine if survivorship for a BIOLOX® delta ceramic on delta ceramic couple used with the PROCOTYL® L acetabular cup is significantly different from all other cementless cups in a large arthroplasty registry. The secondary objective of this study was to analyze patient reported outcomes measures (PROMs) of the subject cup with a minimum five year follow-up.

Objectives

Modularity in total knee arthroplasty, particularly in revisions, is a common method to fit the implants to a patient's anatomy when additional stability or fixation is needed. In such cases, it may be necessary to employ multiple points of modularity to better match the anatomy. Taper junction strength at each of these levels is critical to maintain the mechanical stability of the implant and minimize micromotion. This effect of distributed assembly loads through multiple tapers and the resulting strength of the construct have not been previously evaluated on this revision tibial implant. The purpose of this study was to evaluate the possible dissipation of impaction force through multiple taper connections as compared to a single connection.

Introduction

Total knee replacement (TKR) implant designs and materials have been shown to have a significant impact on tibial insert wear. A medial-pivot (MP) design theoretically should generate less wear due to a large contact area in the medial compartment and lower contact stresses. Synovial fluid aspiration studies have confirmed that a first generation MP TKR system (ADVANCE®, MicroPort Orthopedics Inc., Arlington, TN, USA) generates less wear debris than is seen with other implant designs articulating against conventional polyethylene (CP).

Osteoarthritis (OA) is a common, debilitating joint disease involving degeneration of cartilage and bone. It has been suggested that subtle changes in the molecular structure of subchondral bone may precede cartilaginous changes in the osteoarthritic joint. To explore these changes Raman spectroscopy was employed as a diagnostic tool. Raman spectroscopy measures inelastic scattered laser light produced when photons interact with chemical materials. Resultant changes in wavelength form spectra relative to the chemical composition of the given sample: with bone this includes the mineral and matrix components, unlike conventional X-rays. The aim of our study is to explore the hypothesis: Changes in matrix composition of osteoarthritic subchondral bone can be detected with Raman spectroscopy. pQCT and Raman spectroscopy were employed to determine the bone mineral density (BMD) and bone quality, respectively. Ten medial compartment OA and five control (non-OA) tibial plateaus were interrogated and analysis performed to compare OA to control, and medial to lateral compartments. The subchondral bone of the medial OA compartments had higher BMD (p=0.05) and thickness compared to lateral and control samples. Spectral analysis revealed there is no difference between the medial and lateral compartments within either cohort. However, there is a statistically significant (p=0.02) spectral difference between the OA and control specimens. The detection of bone matrix changes in osteoarthritis using Raman spectroscopy contributes to the understanding of the biochemical signature of subchondral bone across diseased and control tibial plateaus. This technique has potential to shed light on the role of bone in osteoarthritis.

Manufacturing of autologous chondrocytes presents unique challenges, and robust and reliable release assays are required to ensure product quality. We have discovered markers that correctly identify chondrocytes and predict potency. Novel qPCR assays developed with these markers for our Matrix-induced Autologous Chondrocyte Implant product (MACI^® implant) are described. An identity assay must distinguish chondrocytes from potentially contaminating cell types, such as synovial fibroblasts. Microarray analysis of more than 47,000 transcripts led to the discovery of two markers, currently aliased “Cart1” and “Synov1”, that have been characterized as the two most differentially expressed mRNAs between chondrocyte and synovial fibroblast cultures. A potency assay must identify cells that have the potential to form hyaline-like cartilage. We examined expression of critical components of hyaline cartilage during the chondrocyte manufacturing process and in re-differentiation assays. From these studies a gene, which we call “Hyaline1”, was identified as a candidate potency marker. Using an assay measuring the ratio of Cart1:Synov1, a large population study of chondrocyte and synovial fibroblast cultures examined the assay’s suitability for identity classification with our proposed Cart1:Synov1 acceptance boundary. In this study, assay specificity and sensitivity were both observed to be 100%. The utility of the assay was further demonstrated in mixing experiments, where a majority of chondrocytes (in mixtures with synovial fibroblasts) was required to pass the assay acceptance. These results indicate that the assay is useful for determination of both culture identity and culture homogeneity, and thus represents a significant improvement over previous identity assays. The potency assay is also a real-time quantitative RT-PCR assay that measures levels of Hyaline1. Characterization of MACI^® implants indicated that Hyaline1 is stable in long-term culture of chondrocytes but not fibroblasts on ACI-Maix membrane, and is overexpressed in chondrocytes compared fibroblasts that had been recovered from MACI^® implants and tested in various redifferentiation assays. These data suggest that Hyaline1 is predictive of the chondrogenic potential of cells used to manufacture MACI^® implants. After comparing may cell strains, a threshold level which indicates product potency was established. The identification of genetic markers that unambiguously identify cultured chondrocytes has been a long-standing challenge. Another challenge has been the ability to predict re-differentiation capacity of cultured chondrocytes. Modern techniques like whole genome microarray analysis have enabled us to develop novel identity and potency assays for quality control of MACI^® implants.

Introduction: The ‘gold standard’ currently used to assess bone quality is bone mineral density (BMD) measured by Dual Energy X-ray Absorptiometry (DEXA). However BMD accounts for no more than 60 – 70% of bone strength. X-rays are affected primarily by the mineral phase of bone; the organic phase remains essentially invisible. Yet it is known that the material strength and toughness of bone is critically dependent on its organic phase. A Raman spectroscopic technique was used that permitted visualisation of both phases of bone deep to unbroken skin by successfully removing spectral information from the overlying tissues.

Hypothesis: Spectral features of both the mineral and organic phases of bone from different murine genotypes can be measured objectively through the unbroken skin using time-resolved Raman spectroscopy.

Methods: We used an 800 nm probe laser (1 kHz, 1 ps pulses, focussed to 1 mm diameter) with a synchronised 4 ps optical Kerr gate that had a variable picosecond delay that effectively shuttered out photons from the overlying tissues. We measured bone spectra at a point 2mm above the carpus from two mouse genotypes: wildtype and oim/oim (matched for age, sex and weight) at a typical depth 1.1mm. We then repeated the measurements once the overlying tissues had been carefully removed to expose the bones directly. Oim/oim mice produce only homotrimeric collagen I, (á1(I)3), associated with this change in collagen is a poor mineralisation of the bone tissue, making it an ideal model for a this study.

Results: We recorded the main spectral features in both phases of bone and showed that the ratios of spectral bands from the two phases were similar within each genotype, whether measured through the skin or directly from exposed bone. However, there was a significant difference in the same ratios between genotypes associated with a reduced mineralisation in the oim/oim mice; a significant difference that was apparent both directly from bone and through skin. The band associated with CH2 wag of collagen (organic phase) showed a frequency shift between the genotypes.

Discussion: Measurements of the spectra and their analysis were similar whether made directly on bone or transcutaneously. We were able to detect changes in mineralisation between genotypes and, unlike measurements of BMD, we showed also changes in collagen. Since the material strength of bone is critically dependent on collagen, this indicates an appreciable advantage of this technique over DEXA.

Conclusions: This novel technique allowed objective transcutaneous spectral measurements of bone tissue and was able to distinguish between normal and unhealthy bone tissue. With a laser focussed to 1 mm diameter that was readily moveable, these measurements were specific to that site (2 mm proximal to the carpus). After further optimisation, this technology is likely to improve fracture risk assessments in comparison to the use of DEXA alone, opening opportunities for screening in anticipation of the predicted increase in fragility fractures.