Local and systemic concentrations of cobalt (Co) and chromium (Cr) ions may be elevated in patients with accelerated tribo-corrosion at prosthesis bearing surfaces and modular taper junctions. Previous studies by us and others have shown that exposure to these metals negatively affect the viability and function of osteoblasts and osteoclasts in vitro, with implications for bone health. More recently, we have observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum.

Patients with well-functioning MOMHR (n=18) at median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with metal-on-polyethylene total hip arthroplasty (THA). The median circulating concentrations of Co and Cr for the MOMHR group were 2.53µg/L and 2.5µg/L respectively, compared to 0.02µg/L and 0.03µg/L for the THA group. Monocyte fraction of peripheral blood was isolated from these patients, seeded onto dentine wafers and differentiated into osteoclasts using media supplemented with RANKL and M-CSF (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, following which they were treated with OM, autologous serum or serum from the other individual within the matched MOMHR - THA pair, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP stained and quantified for total osteoclast number, number of resorbing osteoclasts and percentage resorption using the CellD Software Package (Olympus, Southend-on-Sea, U.K.).

For cells differentiated in osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced by 30% (P=0.046) compared to THA. Correlation analyses showed that chronic exposure to Co and Cr trends towards negative association with resorption ability of these osteoclasts (r = −0.3, P=0.06). Furthermore, the resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33% (p < 0 .0001), whilst matched THA serum caused a smaller reduction of 14% (p < 0 .01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35% (p < 0 .0001), whilst the matched MOMHR serum also caused a reduction of 21% (p < 0 .0001).

Reduced osteoclastogenic response of precursor cells from patients with higher circulating Co and Cr suggests an inherent change in their potential to differentiate into functional osteoclasts. The data also suggests that functional response of mature osteoclasts generated from patient precursor cells are dependent on the prior systemic metal concentrations and the presence of higher circulating CoCr in patients with MOMHR. These effects are modest, but may explain the subtle increase in systemic bone mineral density and decreased bone turnover observed in patients after 8 years exposure compared to age, sex, and exposure-time matched patients who received a conventional THA.

Introduction

Periprosthetic osteolysis resulting in aseptic loosening is a leading cause for total hip arthroplasty (THA) failure. Individuals vary in their susceptibility to osteolysis, and it is thought that heritable factors contribute to this variation. We conducted two genome-wide association studies to identify genetic risk loci associated with osteolysis and genetic risk loci associated with time to prosthesis failure due to osteolysis.

Introduction

Despite recent national advances in the care for the hip fracture patient, significant morbidity and mortality persists. Some of this morbidity is attributable to the analgesia provided in the hospital setting. The National Institute of Clinical Excellence recommends the use of simple oral analgesia including opioids, with fascia-iliac blocks used as an adjunct. Literature review reveals a paucity of evidence on this topic. The aim of this study was to evaluate the efficacy of fascia iliac blocks through analysis of pre and post-operative opioid usage, post-operative delirium, time to bowel opening and naloxone use.

Purpose

Total and partial joint arthroplasty has been clinically proven to successfully relieve pain and improve function in patients with hip and knee degenerative arthrosis. It has been shown that early return to ambulation correlates well with functional scores. Moreover, the benefits of reduced narcotic use are multi-fold and range from reduced risk of addiction, gastrointenstinal and cardiopulmonary side effects. Establishing realistic pre-operative expectations regarding functional improvement and pain control will nevertheless impact patient satisfaction. Thus, the purpose of this study was to establish safe, achievable and data-driven benchmarks for post-operative ambulation and pain control in patients undergoing elective total joint arthroplasty.

We have previously observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum.

Patients with well-functioning MOMHR (cases, n=18) at a median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with THA (controls, n=18). The monocyte fraction of patient peripheral blood was isolated and differentiated into osteoclasts on dentine wafers using RANKL and M-CSF supplemented media (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, at which point the cells were treated with OM, autologous serum or serum from matched MOMHR/THA donors, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP-stained and quantified using CellD Software Package, Olympus.

When cells were differentiated in standard osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced 22%(p<0.0079) compared to THA. The resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33%(p<0.0001), whilst matched THA serum caused a smaller reduction of 14%(p<0.01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35%(p<0.0001), whilst the matched MOMHR serum also caused a reduction of 21%(p<0.0001).

This data suggests that prior exposure to higher circulating Co and Cr in patients with MOMHR reduces osteoclastogenesis, and that the detrimental effect on the functionality of mature osteoclasts is transferable through the serum. This has implications for systemic bone health of patients with MOMHR or modular taper junctions.

Systemic concentrations of metal ions (cobalt and chromium) are persistently elevated in patients with metal-on-metal hip resurfacing (MOMHR) compared to conventional total hip arthroplasty (THA). Several studies by us and others have described the detrimental effects of metal exposure on survival and function of various cell types in-vitro, but the mechanisms for these effects remain unclear. Epigenetic modifications following chronic metal exposure is a possible mechanism that could mediate these effects. Here we test the methylation status in genomic DNA from MOMHR (“cases”) and THA (“controls”) patient-groups, and its correlation with circulating metal levels.

The cohort consisted of 34 patients with a well-functioning MOMHR at a median follow-up of 9.75 years. These were individually matched for gender, age and time-since-surgery to a non-exposure group consisting of patients with THA. Genomic DNA was isolated from blood samples and cell composition estimated using the ‘estimateCellCounts’ function in ‘minfi R-package’. Methylation was assessed using the Illumina 450k BeadChip array analysing 426,225 probes. Logit model was fitted at each probe with case/control status as independent variable and covariates of gender, age, time-since-surgery, smoking, non-arthroplasty metal exposure, and cell composition. DNA methylation age was assessed using an online calculator (https://dnamage.genetics.ucla.edu/) and comparisons made between cases and controls, and correlated with circulating metal levels.

Cell distributions did not differ between the cases and controls (Wilcoxon test p<0.17) with no probe having an association at 5% FDR. Circulating metal levels and LVEDD also had no association with any probe at 5% FDR. There was no preferential age acceleration between cases and controls (Wilcox p<0.7), and it had no correlation with plasma-chromium or blood-cobalt levels (p<0.9).

In summary, large methylation changes following MOMHR seem to be absent, compared to THA. Future research with larger samples will be needed to clarify the presence and extent of small methylation changes.

Aims

We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks.

Introduction

Although DDH is one of the most common skeletal dysplasias (incidence 1.5 cases per 1000 births), it remains slow and costly to recruit large-scale patient cohorts for powerful genetic association studies. In this work we have successfully used the NJR as a platform to generate a DDH biobank of 907 individuals, upon which we have conducted the first ever genome-wide association study (GWAS) for DDH.

Background-

Health care is best delivered face to face, doctor to patient. However, in some places like Scotland, patients can be in remote areas, far from the nearest health care provider. Medical video conferencing (VC) enables patients and doctors to meet for consultations from wherever they may be without the need for travel, and is already used widely in countries like Australia and Canada.

Cheilectomy of the big toe is offered in the early stages of arthritis affecting the big toe MTPJ, with the understanding that if it fails then a more definitive surgical treatment (e.g. MTPJ fusion or replacement) may be required. When considering treatment options, patients want to know how long will a cheilectomy procedure last. There is limited evidence available about the long term results after cheliectomy, particularly with regards to time to revision surgery. Our aim was to establish the long-term results of cheilectomy with regards to revision surgery and patient-satisfaction over a period of 10 years.

A retrospective review of big toe MTPJ cheilectomies was performed at our institute from 2002 to 2012. The patients were identified using a combination of medical coding system, clinical records, operative log, and radiographs. A systemic review of chielectomy by Roukis (2010) was identified as the clinical standard and revision surgery after cheilectomy, average time to revision and patient satisfaction was assessed.

204 cheilectomies were identified in 192 patients over a period of 10 years. Majority had grade 2 OA (n = 106, 54 %) with grade 3 (n= 65, 33 %) and grade 1 (n= 24, 12 %). The mean follow-up was 4 yrs. (range 6 m to 9 yrs. and 8 m). The overall revision rate to any surgery was 4.4% (n=9), and revision to MTPJ arthrodesis was 3.4% (n =7). The average time to revision was 1 yr. 4 m. 101 patients (55%) were contactable over the phone, and majority (82 %) of them were satisfied with the clinical outcome.

This study shows slightly better overall revision rate (4.4% vs. 8.8%), with revision to arthrodesis being similar (3.4% vs. 3.25%) as compared to the clinical standard. It also suggests that cheilectomy of the big toe can last for a minimum of up to 4 years in 95 % of cases. The 5 % of cases that may require revision surgery are likely to present within the first 2 years. This information is very useful to a patient who wants to know “how long will my cheilectomy last?” whilst making an informed choice

The incidence of wound complications after a hip or a knee replacement is well established, but there is no such data about foot/ankle surgery. Without this data it is difficult to compare performance between different care-providers. It is also difficult to benchmark services that could potentially be provided by a wide range of care providers (chiropodists, podiatrists, podiatric surgeons, general orthopaedic surgeons with a small foot/ankle practice, etc).

Our aim was to establish the incidence of wound complications after foot/ankle surgery and provide a baseline for future comparison.

Our study was done in two parts. First part was to conduct an opinion-survey of BOFAS members with a substantial foot/ankle practice, on wound complications from foot/ankle surgery in their own practice. Second part was to conduct a prospective study on the incidence of wound complications from our own foot/ankle practice. The study was registered as an audit and did not require ethical approval. All wound complications (skin necrosis, wound dehiscence, superficial and deep infections) were recorded prospectively. Record of such data was obtained by an independent observer, and from multiple sources, to avoid under-reporting.

60 % of the responders to our survey had a predominant foot/ankle practice (exclusive or at least 75 % of their practice was foot/ankle surgery) and were included for further analysis of their responses. A large majority of these responders (64%) reported a rate of 2–5 % for superficial infection, and a significant majority (86 %) reported a deep infection rate of less than 2 %. Results from our own practice showed an incidence of superficial infection of 2.8 % and deep infection of 1.5 %.

With increasing focus on clinical outcome measures as an indicator of quality, it is imperative to publish data on wound complications/ infection after foot/ankle surgery, and in the absence of such data, our two-armed study (survey-opinion and prospective audit) provides a useful benchmark for future comparisons.

Pin-on-disk studies have demonstrated the role that cross-shear plays in polyethylene wear. It has been found that applying shear stresses on the polyethylene surface in multiple directions will increase wear rates significantly compared to linear sliding. Hip and knee joint replacements utilize polyethylene as a bearing surface and are subjected to cross-shear motions to various degrees. This is the mechanism that produces wear particles in hip and knee arthroplasty bearings and if excessive may lead to osteolysis, implant loosening, and failure. The amount of cross-shear is dependent on the bearing diameter and the angular motion exerted onto the bearing due to the gait of the patient. This study will determine the effect of sliding curvature (angular change per linear sliding distance) on the wear rate of polyethylene. Virgin polyethylene blocks were machined with a 28mm diameter bearing surface and against 28mm cobalt chromium femoral heads in a hip simulator. Dynamic loading was applied simulating walking gait but the motion differed between testing groups. Typical walking gait testing utilizes 23° biaxial rocking motion, in this study, 10°, 15°, 20°, and 23° biaxial rocking motions resulting in various sliding curvatures. Sliding motion path is described in Figure 1 and is a function of the bearing radius and the rocking angle. With increased rocking angle, the sliding distance reduces per cycle and the sliding path becomes more curved (more angular change per linear distance of sliding). Despite a significant increase in sliding distance at higher rocking angles, wear rates were relatively unchanged and ranged from 57mm3/mc to 62mm3/mc. Wear rates per millimeter increased exponentially with reduced sliding arc radius (smaller rocking angle) as shown in Figure 2. This study suggests that wear of polyethylene is highly dependent on sliding path curvature. The sliding path is largely a function of the bearing diameter and the patient activity. Large bearing diameter implants have been recently introduced to increase joint stability. Sliding distance increases proportional to the bearing radius which has led to some concerns regarding increased wear in larger bearings. However, in vitro wear studies have not shown this trend. Increased bearing diameter also increases the sliding path curvature which this study has shown to cause a reduction in wear roughly proportional to the radius of the bearing. Therefore, the increase in wear due to sliding distance is offset by the reduction in wear caused by the sliding curvature resulting in no significant change in wear with increased bearing diameter. Curved sliding path causes a change in surface shear direction which has been shown to increase wear of polyethylene. This study confirms that increased cross-shear in the form of more angular change per linear sliding distance can increase wear of polyethylene exponentially

Bone related adverse events including failure of implant osseo-integration, periprosthetic fracture, femoral neck narrowing, and unexplained pain occur more frequently following metal-on-metal hip resurfacing (MoMHR) versus total hip arthroplasty (THA). The exact mechanism for the adverse effects is still unclear and may be due to the direct effect on bone cells of metal ions released from the prostheses.

The aim of the present study was to determine the effect of clinically relevant combinations of metal ions on osteoblast cell survival and function. To assess cell proliferation and alkaline phosphatase (ALP) activity of osteoblasts, human osteoblast cells (SaOS-2), were cultured in 96-well plates for 24-hours and then treated with metal ions. Cell proliferation was measured at day 3 and day 7 using MTS assay, whilst ALP activity was assessed at day 3 by measuring pNPP substrate hydrolysis by the cell lysate. Mineralisation ability of the cells was assessed in 24-well plates cultured until day 21 and staining the calcium deposits using Alizarin red. All cultures were treated with the IC50 concentration of Co(II) (135μM) and an equivalent Cr(III) concentration (1Co(II):1Cr(III)).

After 3 days, Co(II) at an IC50 concentration decreased osteoblast proliferation as expected, but no further decrease in proliferation was observed with the 1Co(II):1Cr(III) combination treatment. However, after 7 days, a further significant decrease (P<0.05) in proliferation was observed with the combination treatment compared to Co(II) IC50. A similar significant decrease (P<0.01) was observed for ALP activity at day 3 with 1Co(II):1Cr(III) compared to Co(II) alone. For mineralization, a significant reduction (P<0.0001) was observed for Co(II) IC50 concentration, however no further reduction was seen with the 1Co(II):1Cr(III) combination treatment.

The observed decrease in cell proliferation and ALP activity with combination treatments suggest an additive detrimental effect compared to single ions alone. The mineralisation ability did not show any additive effect due to cell toxicity of chronic exposure to IC50 concentrations calculated from 3 day proliferation cultures. The results suggest that presence of both cobalt and chromium ions in the periprosthetic environment have more severe detrimental effect on osteoblasts than single ions alone and extend our understanding of the periprosthetic bone health.

Background: In developing countries, many patients are seen with neglected, residual or recurrent CTEV. Treatment of resistant & neglected CTEV has been a subject of much controversy as the pathoanatomy becomes complex & the true cause of disability becomes difficult to ascertain at times. We treated such patients by controlled, differential, distraction using Joshi’s external stabilisation system (JESS).

Aim of study: To explore the role & long term results (minimum follow up 3 years) of controlled, differential, distraction using JESS in relapsed & neglected clubfeet.

Methods: 82 patients with 24 bilateral cases (106 feet) treated by JESS at the department of Orthopaedics, KGMU, India from 1992 onwards; followed up for a minimum of 3 years post surgery (average follow up 6.5 years). Patients with non-idiopathic club foot were not included in this study. Outcome evaluation was done by clinical, podographic(footprint), radiological & functional outcomes using Hospital for Joint diseases Orthopaedic Institute functional rating system for clubfoot surgery.

Results: Excellent results were obtained in 63%, good in 30% & poor in 7% of the cases. 21% had a partial relapse with only 5% requiring further surgery for deformity correction. 11% of cases needed further surgery in the form of flexor tenotomies, subtalar & mid-foot fusion for persistent pain

Conclusion: Controlled, differential, fractional distraction with JESS is a safe & effective procedure for neglected, resistant & relapsed CTEV. It is effective even in patients after skeletal maturity in correcting the deformity. The procedure is less invasive and the results are good irrespective of the severity of the deformity or age of the patient.

Introduction: It has been shown in several studies that cytokine (IL-6, TNF-alpha, IL-10, IL-8 etc) concentrations in the peripheral blood are associated with inflammatory activity and surgical trauma. These exhibit more rapid rise and quicker return-to-normal values than either the CRP or the ESR (few hours to few days) and have also been found to be better predictors of postoperative infection compared to CRP/ESR in some studies. Threshold levels of IL-6 after joint replacement surgery have been determined, but levels of other potentially useful cytokines (TNF-alpha, IL-8, IL-10 etc) are not yet known.

Aim: We sought to measure the serum levels of 25 different cytokines before and after hip/knee replacement surgery and identify those associated with postoperative inflammation.

Method: Peripheral venous blood samples were collected from 80 patients undergoing hip/knee replacement. Each patient had one preoperative and three postoperative (total four) blood samples. Samples were stored at −70 degree before being analysed by laser chromatography.

Results: Three out of the 25 cytokines we measured had a significant relationship with postoperative inflammation. The relationship of these three cytokines with a single case of deep infection in our study appeared to be of clinical significance.

Conclusion: It may be possible to use the serum levels of these three cytokines to diagnose periprosthetic infections in the early postoperative period when the CRP and ESR are elevated.