Hip resurfacing may be a useful surgical procedure when patient selection is correct and only implants with superior performance are used. In order to establish a body of evidence in relation to hip resurfacing, pseudotumour formation and its genetic predisposition, we performed a case-control study investigating the role of HLA genotype in the development of pseudotumour around MoM hip resurfacings. All metal-on-metal (MoM) hip resurfacings performed in the history of the institution were assessed. A total of 392 hip resurfacings were performed by 12 surgeons between February 1st 2005 and October 31st 2007. In all cases, pseudotumour was confirmed in the preoperative setting on Metal Artefact Reduction Sequencing (MARS) MRI. Controls were matched by implant (ASR or BHR) and absence of pseudotumour was confirmed on MRI. Blood samples from all cases and controls underwent genetic analysis using Next Generation Sequencing (NGS) assessing for the following alleles of 11 HLA loci (A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPB1, DPA1). Statistical significance was determined using a Fisher's exact test or Chi-Squared test given the small sample size to quantify the clinical association between HLA genotype and the need for revision surgery due to pseudotumour. Both groups were matched for implant type (55% ASR, 45% BHR in both the case and control groups). According to the ALVAL histological classification described by Kurmis et al., the majority of cases (63%, n=10) were found to have group 2 histological findings. Four cases (25%) had group 3 histological findings and 2 (12%) patients had group 4 findings. Of the 11 HLA loci analysed, 2 were significantly associated with a higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) and 4 were noted to be protective against pseudotumour formation (DQA1*03:01:01, DRB1*04:04:01, C*01:02:01, B*27:05:02). These findings further develop the knowledge base around specific HLA genotypes and their role in the development of pseudotumour formation in MoM hip resurfacing. Specifically, the two alleles at higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) in MoM hip resurfacing should be noted, particularly as patient-specific genotype-dependent surgical treatments continue to develop in the future.
Revision hip arthroplasty requires a comprehensive appreciation of abnormal bony anatomy. Advances in radiology and manufacturing technology have made three-dimensional representation of actual osseous anatomy obtainable. These models provide a visual and tactile reproduction of the bony abnormality in question. Life size three dimensional models were manufactured from CT scans of two patients. The first had multiple previous hip arthroplasties and bilateral hip infections. There was a pelvic discontinuity on the right and a severe postero-superior deficiency on the left. The second patient had a first stage revision for infection and recurrent dislocations. Specific metal reduction protocols were used to reduce artefact. The dicom images were imported into Mimics, medical imaging processing software. The models were manufactured using the rapid prototyping process, Selective Laser Sintering (SLS). The models allowed accurate templating using the actual prosthesis templates prior to surgery. Acetabular cup size, augment and buttress sizes, as well as cage dimensions were selected, adjusted and re-sterilised in advance. This reduced operative time, blood loss and improved surgical decision making. Screw trajectory simulation was also carried out on the models, thus reducing the chance of neurovascular injury. With 3D printing technology, complex pelvic deformities can be better evaluated and can be treated with improved precision. The life size models allow accurate surgical simulation, thus improving anatomical appreciation and pre-operative planning. The accuracy and cost-effectiveness of the technique were impressive and its use should prove invaluable as a tool to aid clinical practice.
Osteoporosis is a common skeletal disorder characterised by a reduced bone mass and a progressive micro-architectural deterioration in bone tissue leading to bone fragility and susceptibility to fracture. With a progressively aging population, osteoporosis is becoming an increasingly important public health issue. The Wnt/β-catenin pathway is a major signalling cascade in bone biology, playing a key role in regulating bone development and remodelling, with aberrations in signalling resulting in disturbances in bone mass. To assess the effects of silencing the expression of the Wnt antagonist Dickkopf-1 (Dkk1) on the bone profile of primary human osteoblasts exposed in vitro to 10-8M dexamethasone.Introduction
Objectives
Osteoporosis is a common skeletal disorder characterised by a reduced bone mass and a progressive microarchitectural deterioration in bone tissue leading to bone fragility and susceptibility to fracture. The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in regulating bone development and remodeling, with aberrations in signalling resulting in disturbances in bone mass. Our objectives were to assess the gene expression profile of primary human osteoblasts (HOBs) exposed to dexamethasone with a view to identifying key genes driving bone mass regulation and to assess the effects of the Wnt antagonist Dickkopf-1 (Dkk1) on the bone profile of primary human osteoblasts exposed in vitro to dexamethasone. HOBs were cultured in vitro and exposed to 10–8M dexamethasone over a time course of 4hr, 12hr and 24hr. RNA isolation, cDNA synthesis, in vitro transcription and microarray analysis were performed. Microarray data was validated by quantitative real time RT-PCR. Dkk1 expression was silenced using small interfering RNA (siRNA). Quantitative RT-PCR was performed to confirm gene knockdown. Control and Dex-treated HOBs were compared with respect to bone turnover. Markers of bone turnover analyzed included alkaline phosphatase activity, calcium deposition, osteocalcin expression, along with cell proliferation and cellular apoptosis. Global changes in HOB gene expression were elicited by dexamethasone. Development associated gene pathways were co-ordinately dysregulated with the expression profile of key genes of the Wnt Pathway significantly altered. Dkk1 expression in HOBs was increased in response to dexamethasone exposure with an associated reduction in alkaline phosphatase activity, calcium deposition and osteocalcin expression. Silencing of Dkk1 expression, as confirmed by quantitative RT-PCR, was associated with an increase in alkaline phosphatase activity and calcium deposition, along with increased cell proliferation and reduced cellular apoptosis. Dkk1 is an antagonist of Wnt/β-catenin signalling and plays a key role in regulating bone development and remodeling. Silencing the expression of Dkk1 in primary human osteoblasts has been shown to rescue the effects of dexamethasone-induced bone loss in vitro. The pharmacological targeting of the Wnt/β-catenin signaling pathway offers an exciting opportunity for the development of novel anabolic bone agents to treat osteoporosis and disorders of bone mass.
Case studies: Case 1: Metastatic Leiomyosarcoma Case 2: Metastatic Ewings sarcoma Case 3: Metastatic Epithelioid sarcoma
Surgical treatment of complex deformities necessitates a detailed appreciation of the complex three dimensional abnormal anatomies involved. Preoperative planning for these complex cases traditionally involves x-ray and computerised tomography (CT). These modalities offer only two-dimensional images to represent three-dimensional anatomy. Advances in digital imaging have allowed three-dimensional reconstructions to be derived from CT images. These greatly improve understanding of complex deformities, but will never be able to replace the intuitive understanding that is gained by handling a physical model. The Rapid Prototyping technique Selective Laser Sintering (SLS) is used in the industrial setting to manufacture prototype models from Computer Aided Designs (CAD). This technology can be utilised to convert CT images into accurate three-dimensional physical models of the human bony anatomy. We present the use of SLS modelling to aid in the preoperative planning of complex reconstructive surgery in children. Cases include bladder exstrophy, developmental dysplasia of the hip and reconstruction of a complex elbow malunion. The models provide invaluable visual and tactile information to the operating surgeon, accurately demonstrating the abnormal anatomy in an easily comprehensible manner. They allow estimation of the magnitude and degree of corrections necessary and evaluation of bony deficiencies.