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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 73 - 73
17 Apr 2023
Condell R Flanagan C Kearns S Murphy C
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Despite considerable legacy issues, Girdlestone's Resection Arthroplasty (GRA) remains a valuable tool in the armoury of the arthroplasty surgeon. When reserved for massive lysis in the context of extensive medical comorbidities which preclude staged or significant surgical interventions, and / or the presence of pelvic discontinuity, GRA as a salvage procedure can have satisfactory outcomes. These outcomes include infection control, pain control and post-op function. We describe a case series of 13 cases of GRA and comment of the indications, peri, and post-operative outcomes.

We reviewed all cases of GRA performed in our unit during an 8 year period, reviewing the demographics, indications, and information pertaining to previous surgeries, and post op outcome for each. Satisfaction was based on a binary summation (happy/unhappy) of the patients’ sentiments at the post-operative outpatient consultations.

13 cases were reviewed. They had a mean age of 75. The most common indication was PJI, with 10 cases having this indication. The other three cases were performed for avascular necrosis, pelvic osteonecrosis secondary to radiation therapy and end stage arthritis on a background of profound learning disability in a non-ambulatory patient. The average number of previous operations was 5 (1-10). All 13 patients were still alive post girdlestone. 7 (54%) were satisfied, 6 were not. 3 patients were diabetic. 5 patients developed a sinus tract following surgery.

With sufficient pre-op patient education, early intensive physiotherapy, and timely orthotic input, we feel this procedure remains an important and underrated and even compassionate option in the context of massive lysis and / or the presence of pelvic discontinuity / refractory PJI. GRA should be considered not a marker of failure but as a definitive procedure that gives predictability to patients and surgeon in challenging situations.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 109 - 109
11 Apr 2023
Amado I Hodgkinson T Mathavan N Murphy C Kennedy O
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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic joint injury which is known to cause pathological changes to the osteochondral unit. Articular cartilage degradation is a primary hallmark of OA, and is normally associated with end-stage disease. However, subchondral bone marrow lesions are associated with joint injury, and may represent localized bone microdamage. Changes in the osteochondral unit have been traditionally studied using explant models, of which the femoral-head model is the most common. However, the bone damage caused during harvest can confound studies of microdamage. Thus, we used a novel patellar explant model to study osteochondral tissue dynamics and mechanistic changes in bone-cartilage crosstalk.

Firstly, we characterized explants by comparing patella with femoral head models. Then, the patellar explants (n=269) were subjected to either mechanical or inflammatory stimulus. For mechanical stimulus 10% strain was applied at 0.5 and 1 Hz for 10 cycles. We also studied the responses of osteochondral tissues to 10ng/ml of TNF-α or IL-1β for 24hrs.

In general the findings showed that patellar explant viability compared extremely well to the femoral head explant. Following IL-1β or TNF-α treatment, MMP13, significantly increased three days post exposure, furthermore we observed a decrease in sulfate glycoaminoglycan (sGAG) content. Bone morphometric analysis showed no significant changes. Contrastingly, mechanical stimulation resulted in a significant decrease sGAG particularly at 0.5Hz, where an increase in MMP13 release 24hrs post stimulation and an upregulation of bone and cartilage matrix degradation markers was observed. Furthermore, mechanical stimulus caused increases in TNF-α, MMP-8, VEGF expression.

In summary, this study demonstrates that our novel patella explant model is an excellent system for studying bone-cartilage crosstalk, which responds well to both mechanical and inflammatory stimulus and is thus of great utility in the study of PTOA.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 26 - 26
1 Nov 2021
Amado I Hodgkinson T Murphy C Kennedy O
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Introduction and Objective

Traditionally, osteoarthritis (OA) has been associated mostly with degradation of cartilage only. More recently, it has been established that other joint tissues, in particular bone, are also centrally involved. However, the link between these two tissues remains unclear. This relationship is particularly evident in post-traumatic OA (PTOA), where bone marrow lesions (BMLs), as well as fluctuating levels of inflammation, are present long before cartilage degradation begins. The process of bone-cartilage crosstalk has been challenging to study due to its multi-tissue complexity. Thus, the use of explant model systems have been crucial in advancing our knowledge. Thus, we developed a novel patellar explant model, to study bone cartilage crosstalk, in particular related to subchondral bone damage, as an alternative to traditional femoral head explants or cylindrical core specimens. The commonly used osteochondral explant models are limited, for our application, since they involve bone damage during harvest. The specifics aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response and mechanical stimulation to determine the subsequent developments of PTOA.

Materials and Methods

Lewis rats (n=48) were used to obtain patellar and femoral head explants which were harvested under an institutional ethical approval license. Explants were maintained in high glucose media (containing supplements), under sterile culture conditions. Initially, we characterised undamaged patellar explants and compared them with the commonly used femoral head. First, tissue viability was assessed using an assay of metabolic activity and cell damage. Second, we created chemical and mechanical damage in the form of IL-1B treatment, and mechanical stimulation, to replicate damage. Standard biochemical assays, histological assays and microstructural assays were used to evaluate responses. For chemical damage, explants were exposed to 10ng/ml of IL-1B for 24 hours at 0, 1, 3 and 7 days after harvesting. For mechanical damage, tissues were exposed to mechanical compression at 0.5 Hz, 10 % strain for 10 cycles, for 7 days. Contralateral patellae served as controls. In both groups, sGAG, ADAMTS4, and MMP-13 were measured as an assessment of representative cartilage responses while ALP, TRAP and CTSK were assessed as a representative of bone responses. In addition to this, histomorphometric, and immunohistochemical, evaluations of each explant system were also carried out.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 28 - 28
1 Mar 2021
Amado I Mathavan N Cavanagh B Murphy C Kennedy O
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Osteoarthritis (OA) is a disease that affects both bone and cartilage. Typically, this disease leads to cartilage degradation and subchondral bone sclerosis but the link between the two is unknown. Also, while OA was traditionally thought of as non-inflammatory condition, it now seems that low levels of inflammation may be involved in the link between these responses. This is particularly relevant in the case of Post-Traumatic OA (PTOA), where an initial phase of synovial inflammation occurs after injury. The inflammatory mediator interleukin 1 beta (IL-1B) is central to this response and contributes to cartilage degradation. However, whether there is a secondary effect of this mediator on subchondral bone, via bone-cartilage crosstalk, is not known. To address this question, we developed a novel patellar explant model, to study bone cartilage crosstalk which may be more suitable than commonly used femoral head explants. The specific aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response after joint injury and the subsequent development of PTOA.

Female Sprague Dawley rats (n=48) were used to obtain patellar explants, under an institutional ethical approval license. Patellae were maintained in high glucose media, under sterile culture conditions, with or without IL-1B (10ng/ml), for 7 days. Contralateral patellae served as controls. One group (n= 12) of patellae were assessed for active metabolism, using two both Live and Dead (L/D) staining and an Alamar Blue assay (AB). A second group (n=12) was used for tissue specific biochemical assays for both bone (Alkaline Phosphatase) and cartilage (sulfated proteoglycan and glycosaminoglycan (sGaG)). Finally, a third group (n=28) of explants were used for histologically analysis. Samples were decalcified, embedded in paraffin and sectioned to 7µm thickness, and then stained using H&E; and Safranin O with fast green. Additionally, toluidine blue and alkaline phosphatase staining were also performed.

Our results demonstrate that our system can maintain good explant viability for at least 7 days, but that IL-1B reduces cell viability in patellar cartilage, as measured by both L/D and AB assays after 0, 2, 4 and 7 days in culture. In contrast, sGaG content in cartilage were increased by this treatment. Additionally, ALP, a marker of osteoblastic activity, was increased in IL-1B treated group 4 and 7 days, but was also showed some increase in control groups. Histological analyses showed that IL-1B treatment resulted in reduced proteoglycan staining, demonstrating the powerful effect of this factor in injury response over time.

Thus, we conclude that IL-1B affects both bone and cartilage tissues independently in this system, which may have relevance in understanding bone-cartilage crosstalk after injury and how this is involved in PTOA development.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_1 | Pages 14 - 14
1 Jan 2019
Martin J Murphy C Gregory J Aspden R Riemen A Saunders F
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An increased prevalence of osteoarthritis (OA) in post-menopausal women has led to the suggestion that hormonal factors may play a role in the pathogenesis. This study aims to examine if undergoing a hysterectomy, both with retention and removal of ovaries, predisposes women to OA and secondly if the development is influenced by hormone replacement therapy (HRT).

Statistical shape modelling (SSM) is a method of image analysis allowing for detection of subtle shape variation described by landmark points. Through the generation of linearly independent modes of variation, each image can be described in terms of numerical scores. 149 radiographs from female participants of the Osteoarthritis Initiative (OAI) were examined to compare hip morphology in those who had undergone hysterectomies compared to controls.

No differences were observed in BMI, age, height or weight between groups. ANOVA and Games-Howell post-hoc analysis showed that modes 3 and 5 were statistically significant. Lower mode 3 scores were associated with hysterectomy (p=0.019), with narrowing of the femoral neck and increased acetabular coverage. Lower mode 5 scores were associated with hysterectomy and oophorectomy (p=0.049), displaying reduced coverage of the femoral head, superolateral migration of the femoral head and larger greater trochanter. No associations were observed between HRT use and OA.

The subtle morphologic features of hip OA present in only hysterectomised women suggests undergoing a hysterectomy may be a predisposing factor and a clinical consideration. The use of HRT was not observed to influence the development of OA and thus cannot be suggested as a protective measure.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 135 - 135
1 Nov 2018
Galbraith A Glynn S Coleman C Murphy C
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The international literature base demonstrates that individuals living with diabetes mellitus (DM) are at increased risk of mortality and post-operative complications following hip fracture surgery (HFS) than non-diabetics. Studies investigating databases in American, European or Asiatic populations highlight the impact geography can have on the resultant investigation. We aim to quantify the impact DM has on HFS patients in a single university hospital. The HIPE dataset of fragility fractures occurring in Galway University Hospital from 2014–2016 were analysed and cross referenced with hospital laboratory and public databases. A database of 759 individuals was created including 515 females and 237 males, with a mean age of 78+/−12.2 years, of which 110 patients had DM. The patient length-of-stay (PLOS) was comparable in all groups with patient age being the primary influencing factor. An extended PLOS correlated with an increased long-term mortality. A trend toward increased occurrence of sub-trochanteric fractures was observed in diabetics with fewer periprosthetic and intertrochanteric fractures. Patients with DM had a significant increased risk of post-operative mortality compared to non-diabetics. Males with DM where at a greater risk of death after HFS [HR 2.29, 95% CI 1.26–4.17. p=0.006] than females with DM [HR 1.69, 95% CI 0.99–2.91. p=0.056]. The presence of DM did not directly impact a patient's PLOS or increase the need for a re-operation. DM is associated with increased post-operative patient mortality and may influence the anatomical fracture pattern. This observation will support further investigation into the mechanical and biochemical changes occurring in the femur in individuals living with DM.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 122 - 122
1 Nov 2018
Parle E Tio S Behre A Carey J Murphy C O'Brien T Curtin W Kearns S McCabe J Coleman C Vaughan T McNamara L
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Recent studies have shown that bone mineral distribution is more heterogeneous in bone tissue from an animal model of osteoporosis and osteoporotic human vertebral trabeculae. These tissue alterations may play a role in bone fragility seen in osteoporosis, albeit that they are not detectable by current diagnostic techniques (dual-energy X-ray absorptiometry, DXA). Type II Diabetes Mellitus (T2DM) also increases a patient's fracture risk beyond what can be explained or diagnosed by DXA, and is associated with impaired bone cell function, compromised collagen structure and reduced mechanical properties. However, it is not currently known whether osteoporosis or T2DM leads to an increased mineral heterogeneity in the femoral head of humans, a common osteoporotic fracture site. In this study, we examine bone microarchitecture, mineralisation and mechanical properties of trabecular bone from osteoarthritic, diabetic and osteoporotic patients. We report that while osteoporotic trabecular bone has significantly deteriorated mechanical properties and microarchitecture compared to the other groups, there is also a significant increase in mean mineral content. Moreover, the heterogeneity of the mineral content in osteoporotic bone is significantly higher than osteoarthritic (+35%) and diabetic (+13%) groups. We propose that the compromised architecture following bone loss at the onset of osteoporosis alters the mechanical environment, which initiates compensatory changes in mineral content. We show for the first time that trabecular bone mineralisation is significantly more heterogeneous (+20%) in T2DM compared to osteoarthritic controls. Interestingly, bone microarchitecture and mechanical properties are not significantly different between diabetic and osteoarthritic groups despite this increase in mineral heterogeneity.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIX | Pages 189 - 189
1 Sep 2012
Murphy C O'Flanagan S Keogh P Kenny P
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Introduction

The emergence of a new variant of subtrochanteric stress fractures of the femur affecting patients on oral bisphosphonate therapy has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes, and associated with a characteristic fracture pattern. We undertook a review of this cohort of patients in our service.

Method

A retrospective review was carried out looking for patients with subtrochanteric fractures who were taking oral bisphosphonates presenting with a low velocity injury over a two year period. Clinical data and radiographs were assessed.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVII | Pages 2 - 2
1 May 2012
Murphy C O'Sullivan M
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Introduction

The productivity of trainees, consultants and institutions is frequently judged by the quantity of articles published in medical journals. While personnel may change, an institution should pride itself on its publication record. The aim of the study was to assess the publication history of Irish orthopaedic units over the last 5 years, and to identify patterns of publication.

Methods

Using the same criteria used to differentiate candidates applying for the specialist registrar posts, we performed an extensive Pub Med search of each consultant affiliated with each orthopaedic unit in the country for the last 5 years (2004-2008) to assess the number of publications by each respective consultant and unit. Only the most senior publishing orthopaedic consultant, and the specific institution cited received credit for each paper. Publications were classified by individuals, institutions, publication type and impact factor.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 133 - 133
1 Mar 2012
Murphy C Chen G Winter D Bouchier-Hayes D
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Introduction

Long bone surgery and marrow instrumentation represent significant surgical insults, and may cause severe local and systemic sequelae following both planned and emergent surgery. Preconditioning is a highly conserved evolutionary endogenous protective mechanism, but finding a clinically safe and acceptable method of induction has proven difficult. Glutamine, a known inducer of the heat shock protein (HSP) response, offers pharmacological modulation of injury through clinically acceptable preconditioning. This effect has not been previously demonstrated in an orthopaedic model.

Aims

The aim of the study was to test the hypothesis that glutamine preconditioning protects against the local and systemic effects of long bone trauma in a rodent model.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 43 - 43
1 Mar 2010
Cashman J Murphy C Quinlan W O’Byrne J
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Background: The Wrightington Frusto-Conical 2 (FC2) hip is a tapered stem with derotation flutes designed to withstand physiological loads in normal gait. There is a paucity of literature with regard to the outcome of this stem. This study was designed to determine the medium term outcome of the FC2 hip

Methods: We identified 217 consecutive patients who underwent total hip arthroplasty using the FC2 stem in one institution. Patients were recalled for clinical review. Pain, function and movement were assessed using the Harris Hip Score (HHS) and the D’Aubigne Postel Score. General quality of life and hip specific assessed were made using the WOMAC and SF-36 self directed questionnaires. Statistical analysis was performed.

Results: 86 patients were assessed with a mean follow-up of 7.3 years. Objective clinical outcomes were judged to be good or excellent according to the HHS and the D’Aubigne Postel scores. WOMAC assessment of disease specific outcome demonstrated excellent results particularly in relation to pain and stiffness. SF-36 demonstrated a quality of life score in keeping with an aging study population. There was a 95% survival at 7.3 years.

Conclusions: The FC2 hip has demonstrated a good outcome in the medium term. It shows outcomes that are similar to the Exeter and Charnley hips at this length of followup. Longitudinal follow-up studies are necessary to determine the results of hip implants


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 391 - 391
1 Jul 2008
Rogers B Murphy C Cannon S Briggs T
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Introduction: The load bearing status of articular cartilage has been shown to affect its biochemical composition. This study investigates the topographical variation of glycosaminoglycan (GAG) relative to DNA content in human distal femoral articular cartilage.

Methods: 26-paired specimens of distal femoral articular cartilage, from weight bearing and non-weight regions, were obtained from thirteen patients undergoing amputation. Following papain enzyme digestion, spectropho-tometric (GAG) and fluorometric (DNA) assays assessed the biochemical composition of the explants. Data was analysed using a paired T test.

Results: Despite no significant differences in absolute DNA concentrations, weight-bearing regions of articular cartilage showed a significantly higher concentration of GAG relative to DNA compared with non-weight bearing areas (p=0.021).

Discussion: This study suggests that chondrocytes in weight bearing regions of human articular cartilage produce a greater quantity of GAG than those located in non-weight bearing areas. We conclude that mechanical loading is essential in maintaining the biochemical composition of human articular cartilage.