There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA. A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers. During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage. This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.
Fascia iliaca compartment block (FIB), performed in the Emergency Department (A&E) in patients presenting with femoral neck fracture, has gained increasing recognition as an adjunctive analgesic. The purpose of this study was to investigate whether FIB significantly reduced the requirement for systemic opiates in the pre-operative setting. Analgesia requirements for all patients admitted with fractured neck of femur to one unit over a four month period were gathered prospectively. 33% patients had received FIB at diagnosis in ED, dependant on the expertise of the attending physician. Morphine requirements on arrival on the ward between groups were analysed. Over a four month period 144 patients were admitted with fractured neck of femur. Over this time period, introduction of an informal educational programme in A&E increased the incidence of FIB provision at diagnosis and reduced the average amount of morphine administered. Administration of FIB reduced the average morphine requirement in A&E by 56%, when compared with those who received systemic analgesia alone (CI 0.4–3.5, p=0.014). No adverse effects were reported with FIB. Fascia Iliaca Compartment Block is a safe and effective method of providing analgesia to patients with fractured neck of femur and reduces morphine requirement.
Between January 1996 and July 2002, 60 patients (65 hips) were treated in our unit by 5 consultant surgeons using the Corin Cobalt-Chrome metal-on-metal hip resurfacing. 41 procedures were performed on male patients and 24 female. All 65 cases used the Cormet Hip resurfacing (Corin, UK). Of these, 12 cases (18.5%) have required revision for mechanical failure. 5 of these patients were male and 7 female. The time to failure was defined as the interval between the date of primary and the date of revision surgery. The mean time to failure was 10.2 months (range 48 hours to 53 months). 8 out of 12 patients required revision within 6 months of the primary procedure. The mean age at the time of revision was 56 years (range 22–71 years). The commonest mechanism of failure in our series is fractured neck of femur and 4 out of the 6 fractured neck of femur occurred in females over the age of 60. Only 12 of our primary hip resurfacings were women over 60 with the result that 33% of this group were complicated by fractured neck of femur. In 4 cases, the indication for revision was acetabular loosening. One patient underwent revision surgery for chronic pain of unknown aetiology and one developed progressive avascular necrosis of the femoral head. Our early results suggest that the procedure is operator-dependent and associated with a steep learning curve. The procedure would appear to be contraindicated in women over 60 and others at risk of osteoporosis.
One of the most commonly cited advantages of hip resurfacing is the technical ease of revision surgery on the femoral side of the joint. It is therefore reasonable to suggest that such surgery ought to be associated with reduced operative times, reduced blood loss and more rapid mobilisation than conventional hip revision. However, there is little objective evidence in the literature to support this view. In our own unit, 6 consultants have now revised 15 hip resurfacings (13 Corins and 2 MMT Birmingham Hip Resurfacings). A retrospective study of the hospital records was performed to compare three well recorded parameters 1) On table operative times 2) Post Operative blood transfusion requirement 3) In patient length of stay. Average on table time was 195 minutes for conventional THR revision and 120 minutes for revision of resurfacing i.e. a 1 third reduction in theatre time for resurfacing with attendant advantages in costs and risks. However, post operative length of stay was little different between the two groups. Average blood transfusion requirement was 4.6 units for conventional THR revision (n=190) and 0.9 units for revision of resurfacing. However, these crude figures do not take into account the difference in physiological state between the two groups of patients. A more complex comparison of age matched revision THR patients shows and average transfusion requirement of 1.8 to 2.2 units for revision of THR versus 0.9 units for revision resurfacing. In conclusion, there is now objective evidence of the advantages of resurfacing in the revision situation but that these advantages are more modest than those anticipated.
In recent years there has been a resurgence of interest in the concept of hip resurfacing. Since 1996, we have treated 60 patients (65 hips) with the Corin Hip Resurfacing. Of the 65 primary procedures, 13 have now required revision. 1 case was complicated by early deep infection and 12 (17%) for mechanical failure. 5 of these patients were male and 8 female. Mean time to failure was 11 months (range 48 hours to 53 months). 8 out of the 12 mechanical failures required revision within 6 months of the primary procedure. Mean age of the revision patients was 57 years (range 22 – 71 years). The most common failure modality (6 cases) was fractured neck of femur. 4 out of 6 of these cases occurred in women over 60 years of age. All of these fractures occurred without a specific history of trauma. Since only 12 patients were women over 60, 1 in 3 women over 60 years of age in our series were complicated by fractured neck of femur. In 4 cases, the indication for revision was acetabular loosening. One patient had ongoing pain of unknown aetiology and one developed progressive avascular necorsis of the femoral head with subsequent collapse. Of the 12 cases requiring revision for mechanical failure, two cases required revision of the femoral component only and this was performed using the stemmed modular CTI prosthesis produced by Corin for this purpose. Three cases required revision of the socket only and the others were revised to total joint replacement. The one case of early deep infection was treated by two stage revision. There were no dislocations in our series and there was no evidence of metallosis. Not for the first time in the history of orthopaedics, a DGH has been unable to repeat the excellent results reported by a specialist centre with a new technique. However, analysis of the above data has led us to believe that our results may be much improved by careful patient selection. It is also apparent that formal revision strategies need to be developed for hips resurfacing.
