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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_9 | Pages 11 - 11
16 May 2024
Kendal A Brown R Loizou C Rogers M Sharp R Carr A
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Tendinopathy can commonly occur around the foot and ankle resulting in isolated rupture, debilitating pain and degenerative foot deformity. The pathophysiology and key cells involved are not fully understood. This is partly because the dense collagen matrix that surrounds relatively few resident cells limits the ability of previous techniques to identify and target those cells of interest. In this study, we apply novel single cell RNA sequencing (CITE-Seq) techniques to healthy and tendinopathic foot/ankle tendons. For the first time we have identified multiple sub-populations of cells in human tendons. These findings challenge the view that there is a single principal tendon cell type and open new avenues for further study. Healthy tendon samples were obtained from patients undergoing tendon transfer procedures; including tibialis posterior and FHL. Diseased tendon samples were obtained during debridement of intractable Achilles and peroneal tendinopathy, and during fusion of degenerative joints. Single cell RNA sequencing with surface proteomic analysis identified 10 sub-populations of human tendon derived cells. These included groups expressing genes associated with fibro-adipogenic progenitors (FAPs) as well as ITGA7+VCAM1- recently described in mouse muscle but, as yet, not human tendon. In addition we have identified previously unrecognised sub-classes of collagen type 1 associated tendon cells. Each sub-class expresses a different set of extra-cellular matrix genes suggesting they each play a unique role in maintaining the structural integrity of normal tendon. Diseased tendon harboured a greater proportion of macrophages and cytotoxic lymphocytes than healthy tendon. This inflammatory response is potentially driven by resident tendon fibroblasts which show increased expression of pro-inflammatory cytokines. Finally, identification of a previously unknown sub-population of cells found predominantly in tendinopathic tissue offers new insight into the underlying pathophysiology. Further work aims to identify novel proteins targets for possible therapeutic pathways


Bone & Joint Research
Vol. 7, Issue 5 | Pages 373 - 378
1 May 2018
Johnson-Lynn SE McCaskie AW Coll AP Robinson AHN

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1


Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.


Introduction. The prevalence of symptomatic osteoarthritis (OA) in the knee is 11–11% compared to 3.4–4.4% in the ankle. In addition to this, 70% of ankle arthritis is post-traumatic while the vast majority of knee arthritis is primary OA. Several reports have previously implicated biochemical differences in extracellular matrix composition between these joint cartilages; however, it is unknown whether there is an inherent difference in their transcriptome and how this might affect their respective functionality under load, inflammatory environment etc. Therefore, we have analysed the transcriptome of ankle and knee cartilage chondrocytes to determine whether this could account for the lower prevalence and altered aetiology of ankle OA. Methods. Human full-depth articular cartilage was taken from the talar domes (n=5) and the femoral condyles (n=5) following surgical amputation. RNA was extracted and next generation sequencing (NGS) performed using the NextSeq®500 system. Statistical analysis was performed to identify differentially regulated genes (p adj < 0.05). Data was analysed using Integrated Pathway Analysis software and genes of interest validated by quantitative PCR. Results. 809 genes were differentially expressed in this NGS study: 781 genes were significantly up-regulated and 27 significantly down-regulated in ankle cartilage with respect to knee. Preliminary analysis has identified several pathways which are differentially regulated including ‘inflammation mediated by cytokines’, ‘glutamate receptor pathway, ‘heterotrimeric-G-protein signalling pathways’, ‘WNT signalling’ and ‘integrin signalling’. Discussion. This is the first report identifying genes that are differentially expressed in ankle cartilage compared to the knee. Validation is currently being performed to ascertain the importance of these gene changes and correlation with their protein expression in the different joints. An understanding of the inherent biological differences in the cartilage between these two joints will provide invaluable insight into why the ankle is relatively spared from primary OA and the majority of ankle arthritis occurs following trauma


Bone & Joint Research
Vol. 9, Issue 9 | Pages 613 - 622
1 Sep 2020
Perucca Orfei C Lovati AB Lugano G Viganò M Bottagisio M D’Arrigo D Sansone V Setti S de Girolamo L

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Methods

A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXII | Pages 59 - 59
1 May 2012
Paringe V Vannet N Ferran N Gandour A
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ECSWT has been on the medical horizon for last 30 years mainly in urology for urolithiasis and has found a parallel use in orthopaedics for various chronic soft tissue conditions like Tendoachilles tendinoses and plantar fasciitis etc. ECSWT acts a piezoelectric device releasing acoustic energy and causing micro-trauma activating cytokine mediated response stimulating local angiogenesis and tissue repair. Methodology. 56 patients were recruited for the trial after ethics approval was achieved. The diagnosis was confirmed with ultrasound scan and measuring the width of the swelling and the local hypervascularity. The cohort of the patients was randomised in groups for physiotherapy [n=23] and shockwave therapy [n= 23]. The patient groups with shockwave therapy received a 3-week treatment with typical 2000 impulses per session once a week and physiotherapy group was subjected to eccentric loading exercises. Patients were assessed at 12 week with AOFAS, VISA-A scores and repeat ultrasound scan. Results. The average age of the average age was 51 years [36- 73 years] Mean duration of symptoms prior to treatment was 25 months (range 6-60 months). AOFAS scores increased in both groups: from 64□86 in the ECSWT group and 72□79 in the physiotherapy group. VISA-A scores also increased in both groups from 39□73 in the ECSWT group and from 36□56 in the physiotherapy group. Scores were significantly higher in the ECWST group post treatment. The ultrasound scan findings suggested the tendon girth receding from 10.9 mm□9.9 mm in physiotherapy group while 9.8 mm□8.7 mm in the ECSWT group with hypervascularity decreasing from marked to mild in both groups. Statistical significance was established using SPSS 16 p < 0.001in post treatment group. Conclusion. Clinically significant improvement was found in the patients treated with ECSWT as compared to the physiotherapy sessions while radiological evidence showed parallel improvement in both the groups


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 345 - 351
1 Mar 2020
Pitts C Alexander B Washington J Barranco H Patel R McGwin G Shah AB

Aims

Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion.

Methods

We retrospectively reviewed the medical records of 101 patients who underwent TTC fusion at the same institution between 2011 and 2019. Risk ratios (RRs) associated with age, sex, diabetes, cardiovascular disease, smoking, preoperative ankle deformity, and the use of bone graft during surgery were related to the postoperative complications. We determined from these data which pre- and perioperative factors significantly affected the outcome.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 809 - 813
1 Jun 2015
Butt DA Hester T Bilal A Edmonds M Kavarthapu V

Charcot neuro-osteoarthropathy (CN) of the midfoot presents a major reconstructive challenge for the foot and ankle surgeon. The Synthes 6 mm Midfoot Fusion Bolt is both designed and recommended for patients who have a deformity of the medial column of the foot due to CN. We present the results from the first nine patients (ten feet) on which we attempted to perform fusion of the medial column using this bolt. Six feet had concurrent hindfoot fusion using a retrograde nail. Satisfactory correction of deformity of the medial column was achieved in all patients. The mean correction of calcaneal pitch was from 6° (-15° to +18°) pre-operatively to 16° (7° to 23°) post-operatively; the mean Meary angle from 26° (3° to 46°) to 1° (1° to 2°); and the mean talometatarsal angle on dorsoplantar radiographs from 27° (1° to 48°) to 1° (1° to 3°).

However, in all but two feet, at least one joint failed to fuse. The bolt migrated in six feet, all of which showed progressive radiographic osteolysis, which was considered to indicate loosening. Four of these feet have undergone a revision procedure, with good radiological evidence of fusion. The medial column bolt provided satisfactory correction of the deformity but failed to provide adequate fixation for fusion in CN deformities in the foot.

In its present form, we cannot recommend the routine use of this bolt.

Cite this article: Bone Joint J 2015; 97-B:809–13


The Bone & Joint Journal
Vol. 96-B, Issue 2 | Pages 164 - 171
1 Feb 2014
Hannon CP Smyth NA Murawski CD Savage-Elliott BA Deyer TW Calder JDF Kennedy JG

Osteochondral lesions (OCLs) occur in up to 70% of sprains and fractures involving the ankle. Atraumatic aetiologies have also been described. Techniques such as microfracture, and replacement strategies such as autologous osteochondral transplantation, or autologous chondrocyte implantation are the major forms of surgical treatment. Current literature suggests that microfracture is indicated for lesions up to 15 mm in diameter, with replacement strategies indicated for larger or cystic lesions. Short- and medium-term results have been reported, where concerns over potential deterioration of fibrocartilage leads to a need for long-term evaluation.

Biological augmentation may also be used in the treatment of OCLs, as they potentially enhance the biological environment for a natural healing response. Further research is required to establish the critical size of defect, beyond which replacement strategies should be used, as well as the most appropriate use of biological augmentation. This paper reviews the current evidence for surgical management and use of biological adjuncts for treatment of osteochondral lesions of the talus.

Cite this article: Bone Joint J 2014;96-B:164–71.


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 305 - 313
1 Mar 2013
Ribbans WJ Collins M

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases.

This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry.

Cite this article: Bone Joint J 2013;95-B:305–13.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 10 | Pages 1322 - 1325
1 Oct 2009
El-Gafary KAM Mostafa KM Al-adly WY

Charcot osteoarthropathy of the foot is a chronic and progressive disease of bone and joint associated with a risk of amputation. The main problems encountered in this process are osteopenia, fragmentation of the bones of the foot and ankle, joint subluxation or even dislocation, ulceration of the skin and the development of deep sepsis. We report our experience of a series of 20 patients with Charcot osteoarthropathy of the foot and ankle treated with an Ilizarov external fixator. The mean age of the group was 30 years (21 to 50). Diabetes mellitus was the underlying cause in 18 patients. Five had chronic ulcers involving the foot and ankle. Each patient had an open lengthening of the tendo Achillis with excision of all necrotic and loose bone from the ankle, subtalar and midtarsal joints when needed. The resulting defect was packed with corticocancellous bone graft harvested from the iliac crest and an Ilizarov external fixator was applied. Arthrodesis was achieved after a mean of 18 weeks (15 to 20), with healing of the skin ulcers. Pin track infection was not uncommon, but no frame had to be removed before the arthrodesis was sound.

Every patient was able to resume wearing regular shoes after a mean of 26.5 weeks (20 to 45).


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 907 - 914
1 Jul 2009
Koivu H Kohonen I Sipola E Alanen K Vahlberg T Tiusanen H

Between 2002 and 2008, 130 consecutive ankles were replaced with an hydroxyapatite (HA) and titanium-HA-coated Ankle Evolutive System total ankle prosthesis. Plain radiographs were analysed by two independent observers. Osteolytic lesions were classified by their size and location, with cavities > 10 mm in diameter considered to be ‘marked’. CT scanning was undertaken in all patients with marked osteolysis seen on the plain radiographs.

Osteolytic lesions were seen on the plain films in 48 (37%) and marked lesions in 27 (21%) ankles. The risk for osteolysis was found to be 3.1 (95% confidence interval 1.6 to 5.9) times higher with implants with Ti-HA porous coating.

Care should be taken with ankle arthroplasty until more is known about the reasons for these severe osteolyses.