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Bone & Joint Research
Vol. 3, Issue 3 | Pages 82 - 88
1 Mar 2014
Abdel MP Morrey ME Barlow JD Grill DE Kolbert CP An KN Steinmann SP Morrey BF Sanchez-Sotelo J

Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 291 - 295
1 Mar 2005
Farmer SE Woollam PJ Patrick JH Roberts AP Bromwich W


Bone & Joint Research
Vol. 6, Issue 3 | Pages 162 - 171
1 Mar 2017
Walker JA Ewald TJ Lewallen E Van Wijnen A Hanssen AD Morrey BF Morrey ME Abdel MP Sanchez-Sotelo J

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193


Bone & Joint Research
Vol. 9, Issue 6 | Pages 302 - 310
1 Jun 2020
Tibbo ME Limberg AK Salib CG Turner TW McLaury AR Jay AG Bettencourt JW Carter JM Bolon B Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen AJ Abdel MP

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1168 - 1176
1 Sep 2019
Calder PR McKay JE Timms AJ Roskrow T Fugazzotto S Edel P Goodier WD

Aims. The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients. Patients and Methods. A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications. Results. The mean lengthening was 4.65 cm (1.5 to 8) in the antegrade group and 4.64 cm (1.6 to 8) in the retrograde group. Of the 107 lengthenings, 100 had sufficient datapoints to calculate the mean HI. This was 31.6 days/cm (15 to 108). There was a trend toward a lower (better) HI with an antegrade nail and better outcomes in adolescent patients, but these were not statistically significant. Hip and knee ROM was maintained and/or improved following commencement of femoral lengthening in 44 patients (60%) of antegrade nails and 13 patients (38%) of retrograde nails. In female patients, loss of movement occurred both earlier and following less total length achieved. Minor implant complications included locking bolt migration and in one patient deformity of the nail, but no implant failed to lengthen and there were no deep infections. Three patients had delayed union, five patients required surgical intervention for joint contracture. Conclusion. This study confirms excellent results in femoral lengthening with antegrade and retrograde Precice nails. There is a trend for better healing and less restriction in hip and knee movement following antegrade nails. There are clinical scenarios, that mandate the use of a retrograde nail. However, when these are not present, we recommend the use of antegrade nailing. Cite this article: Bone Joint J 2019;101-B:1168–1176


Bone & Joint Research
Vol. 7, Issue 3 | Pages 213 - 222
1 Mar 2018
Tang X Teng S Petri M Krettek C Liu C Jagodzinski M

Objectives. The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo. Methods. Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents. Results. Dexamethasone maintained the viability and promoted the proliferation of AFib. Diclofenac decreased the viability and inhibited the cell proliferation during the first week of cultivation. However, decorin inhibited AFib proliferation and downregulated the expressions of fibrotic markers. Additionally, decorin could improve the flexion contracture angle and inhibit the deposition of interstitial matrix components in the rabbit joint model. Conclusion. Decorin decreased the expression of myofibroblast markers in AFib, inhibited the proliferation of AFib, and prevented the initial procedure of arthrofibrosis in vivo, suggesting that decorin could be a promising treatment to inhibit the development of arthrofibrosis. Cite this article: X. Tang, S. Teng, M. Petri, C. Krettek, C. Liu, M. Jagodzinski. The effect of anti-inflammatory and antifibrotic agents on fibroblasts obtained from arthrofibrotic tissue: An in vitro and in vivo study. Bone Joint Res 2018;7:213–222. DOI: 10.1302/2046-3758.73.BJR-2017-0219.R2


Bone & Joint Research
Vol. 5, Issue 1 | Pages 11 - 17
1 Jan 2016
Barlow JD Morrey ME Hartzler RU Arsoy D Riester S van Wijnen AJ Morrey BF Sanchez-Sotelo J Abdel MP

Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (. sd. ) 11) vs 37° (. sd. 14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Open
Vol. 4, Issue 1 | Pages 19 - 26
13 Jan 2023
Nishida K Nasu Y Hashizume K Okita S Nakahara R Saito T Ozaki T Inoue H

Aims

There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA).

Methods

We retrospectively reviewed the records of 26 elbows of 21 patients with RA who were aged less than 50 years who underwent primary TEA with an unlinked elbow prosthesis. The mean patient age was 46 years (35 to 49), and the mean follow-up period was 13.6 years (6 to 27). Outcome measures included pain, range of motion, Mayo Elbow Performance Score (MEPS), radiological evaluation for radiolucent line and loosening, complications, and revision surgery with or without implant removal.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 1090 - 1096
1 Aug 2008
Chotel F Unnithan A Chandrasekar CR Parot R Jeys L Grimer RJ

We have analysed the pattern of symptoms in patients presenting with synovial sarcoma to identify factors which led to long delays in diagnosis. In 35 children, the early symptoms and the results of clinical and radiological investigation were reviewed, along with the presumed diagnoses. The duration of symptoms was separated into patient delay and doctor delay. Only half of the patients had one or more of the four clinical findings suggestive of sarcoma according to the guidance of the National Institute for Clinical Excellence at the onset of symptoms. Of the 33 children for whom data were available, 16 (48.5%) presented with a painless mass and in ten (30.3%) no mass was identified. Seven (21.2%) had an unexplained joint contracture. Many had been extensively investigated unsuccessfully. The mean duration of symptoms was 98 weeks (2 to 364), the mean patient delay was 43 weeks (0 to 156) and the mean doctor delay was 50 weeks (0 to 362). The mean number of doctors seen before referral was three (1 to 6) and for 15 patients the diagnosis was obtained after unplanned excision. Tumours around the knee and elbow were associated with a longer duration of symptoms and longer doctor delay compared with those at other sites. Delays did not improve significantly over the period of our study of 21 years, and we were unable to show that delay in diagnosis led to a worse prognosis. Our findings highlight the variety of symptoms associated with synovial sarcoma and encourage greater awareness of this tumour as a potential diagnosis in childhood


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 815 - 820
1 Jul 2023
Mitchell PD Abraham A Carpenter C Henman PD Mavrotas J McCaul J Sanghrajka A Theologis T

Aims

The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems.

Methods

A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation.


The Bone & Joint Journal
Vol. 104-B, Issue 11 | Pages 1273 - 1278
1 Nov 2022
Chowdhury JMY Ahmadi M Prior CP Pease F Messner J Foster PAL

Aims

The aim of this retrospective cohort study was to assess and investigate the safety and efficacy of using a distal tibial osteotomy compared to proximal osteotomy for limb lengthening in children.

Methods

In this study, there were 59 consecutive tibial lengthening and deformity corrections in 57 children using a circular frame. All were performed or supervised by the senior author between January 2013 and June 2019. A total of 25 who underwent a distal tibial osteotomy were analyzed and compared to a group of 34 who had a standard proximal tibial osteotomy. For each patient, the primary diagnosis, time in frame, complications, and lengthening achieved were recorded. From these data, the frame index was calculated (days/cm) and analyzed.


Bone & Joint 360
Vol. 11, Issue 4 | Pages 21 - 25
1 Aug 2022


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 236 - 240
1 Feb 2005
Belthur MV Bradish CF Gibbons PJ

Between 1990 and 2001, 24 children aged between 15 months and 11 years presented with late orthopaedic sequelae after meningococcal septicaemia. The median time to presentation was 32 months (12 to 119) after the acute phase of the disease. The reasons for referral included angular deformity, limb-length discrepancy, joint contracture and problems with prosthetic fitting. Angular deformity with or without limb-length discrepancy was the most common presentation. Partial growth arrest was the cause of the angular deformity. Multiple growth-plate involvement occurred in 14 children. The lower limbs were affected much more often than the upper. Twenty-three children underwent operations for realignment of the mechanical axis and limb-length equalisation. In 15 patients with angular deformity around the knee the deformity recurred. As a result we recommend performing a realignment procedure with epiphysiodesis of the remaining growth plate when correcting angular deformities


Bone & Joint Research
Vol. 11, Issue 1 | Pages 32 - 39
27 Jan 2022
Trousdale WH Limberg AK Reina N Salib CG Thaler R Dudakovic A Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen A Abdel MP

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Methods

A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 704 - 710
1 Apr 2021
van den Berge BA Werker PMN Broekstra DC

Aims

With novel promising therapies potentially limiting progression of Dupuytren’s disease (DD), better patient stratification is needed. We aimed to quantify DD development and progression after seven years in a population-based cohort, and to identify factors predictive of disease development or progression.

Methods

All surviving participants from our previous prevalence study were invited to participate in the current prospective cohort study. Participants were examined for presence of DD and Iselin’s classification was applied. They were asked to complete comprehensive questionnaires. Disease progression was defined as advancement to a further Iselin stage or surgery. Potential predictive factors were assessed using multivariable regression analyses. Of 763 participants in our original study, 398 were available for further investigation seven years later.


Bone & Joint 360
Vol. 10, Issue 6 | Pages 18 - 20
1 Dec 2021


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 6 | Pages 891 - 894
1 Aug 2003
Kobayashi D Kumagai H Satsuma S

We describe the treatment of three boys with cavernous lymphangioma of the legs. The suggested guidelines for treatment are extensive surgical resection, although complete resection is usually impossible, and approximately two weeks after the operation aspiration of serous fluid which has accumulated at the operation site, followed by injection of OK-432 (Picibanil). There was pyrexia and local inflammation for several days but the accumulation of serous fluid disappeared after the injection. There were no complications with no recurrence, joint contracture, or pain during a mean follow-up of 48 months (24 to 72). We conclude that an injection of OK-432 after surgical resection of cavernous lymphangioma of the legs in children is an effective treatment


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1088 - 1091
1 Aug 2007
Khan MA

In developed countries, children with cerebral palsy are treated from the time of diagnosis. This is usually not the case in developing countries where such patients often present at an age when it is traditionally believed that if walking has not already commenced, it is unlikely to. This study reports the outcome of the surgical treatment of 85 spastic diplegic patients at a mean of 8.5 years (5 to 12). All presented as untreated non-walkers and had achieved sitting balance by the age of five to six years. They underwent single-event multilevel surgery followed by physiotherapy and orthotic support. For outcome assessment, a modified functional walking scale was used at a mean of 3.5 years (2 to 5) post-operatively. At all levels, static joint contractures had resolved almost completely. All patients improved and became walkers, 18 (21.2%) as exercise, 39 (45.9%) as household and 28 (33%) as community walkers. This study shows that children with cerebral palsy who cannot walk and have not been treated can be helped by single-event multilevel surgery, provided that inclusion criteria are followed and a structural, supervised rehabilitation programme is in place