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The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1115 - 1121
1 Aug 2007
Messick KJ Miller MA Damron LA Race A Clarke MT Mann KA

The role of vacuum mixing on the reduction of porosity and on the clinical performance of cemented total hip replacements remains uncertain. We have used paired femoral constructs prepared with either hand-mixed or vacuum-mixed cement in a cadaver model which simulated intra-operative conditions during cementing of the femoral component. After the cement had cured, the distribution of its porosity was determined, as was the strength of the cement-stem and cement-bone interfaces. The overall fraction of the pore area was similar for both hand-mixed and vacuum-mixed cement (hand 6%; vacuum 5.7%; paired t-test, p = 0.187). The linear pore fractions at the interfaces were also similar for the two techniques. The pore number-density was much higher for the hand-mixed cement (paired t-test, p = 0.0013). The strength of the cement-stem interface was greater with the hand-mixed cement (paired t-test, p = 0.0005), while the strength of the cement-bone interface was not affected by the conditions of mixing (paired t-test, p = 0.275). The reduction in porosity with vacuum mixing did not affect the porosity of the mantle, but the distribution of the porosity can be affected by the technique of mixing used


Bone & Joint Research
Vol. 6, Issue 4 | Pages 196 - 203
1 Apr 2017
Jin Y Chen X Gao ZY Liu K Hou Y Zheng J

Objectives. This study aimed to explore the role of miR-320a in the pathogenesis of osteoarthritis (OA). Methods. Human cartilage cells (C28/I2) were transfected with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL-1β. Subsequently the expression of collagen type II alpha 1 (Col2α1) and aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay, qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co-transfected with miR-320a and PBX3 expressing vector, or cells were transfected with miR-320a and treated with a nuclear factor kappa B (NF-κB) antagonist MG132. The changes in Col2α1 and ACAN expression, and in sGAG and MMP-13 concentrations, were measured again. Statistical comparisons were made between two groups by using the two-tailed paired t-test. Results. Expression of miR-320a was elevated in OA cartilage tissues and chondrocytes, and in IL-1β-stimulated C28/I2 cells (p < 0.05 or p < 0.01). MiR-320a overexpression enhanced IL-1β-induced down-regulation of Col2α1 and ACAN and sGAG, and increased the IL-1β-induced overexpression of MMP-13 (p < 0.01). PBX3 was a direct target of miR-320a. PBX3 and MG132 co-transfection attenuated the effects of miR-320a on the expression of Col2α1, ACAN, sGAG and MMP-13(p < 0.01). Conclusion. Overexpression of miR-320a might enhance IL-1β-induced cartilage degradation factors. These effects might be via targeting PBX3 and regulating NF-κB. Cite this article: Y. Jin, X. Chen, Z. Y. Gao, K. Liu, Y. Hou, J. Zheng. The role of miR-320a and IL-1β in human chondrocyte degradation. Bone Joint Res 2017;6:–203. DOI: 10.1302/2046-3758.64.BJR-2016-0224.R1


Bone & Joint Research
Vol. 6, Issue 4 | Pages 208 - 215
1 Apr 2017
Decambron A Manassero M Bensidhoum M Lecuelle B Logeart-Avramoglou D Petite H Viateau V

Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion. Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1


Bone & Joint Research
Vol. 5, Issue 10 | Pages 492 - 499
1 Oct 2016
Li X Li M Lu J Hu Y Cui L Zhang D Yang Y

Objectives. To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention. Materials and Methods. The study included 20 male Sprague-Dawley rats, ten in the young group (aged four to five weeks) and ten in the adult group (aged 18 to 20 weeks). In each rat, the upper-left first molar was subjected to a seven-day orthodontic force loading followed by a seven-day retention period. The upper-right first molar served as a control. The amount of orthodontic tooth movement was measured after seven-day force application and seven-day post-orthodontic retention. The expression levels of RANKL and the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were evaluated on day 7 (end of mechanical force loading) and day 14 (after seven days of post-orthodontic retention). Statistical analysis was performed using the t-test, and significance was set at p < 0.05. Results. There was no significant difference between the amount of tooth movement in the young group (0.96, standard deviation (. sd. ) 0.30mm) and that in the adult group (0.80mm, . sd. 0.28) (p > 0.05) after the seven-day force application. On the compression side, the expression of RANKL and TRAP-positive osteoclasts in both the young and the adult groups increased after the application of force for seven days, and then decreased at the end of the seven-day retention period. However, by the end of the period, the expression of RANKL on the compression side dropped to the control level in the young group (p > 0.05), while it was still higher than that on the control side in the adult group (p < 0.05). The expression of RANKL on the compression side did not show significant difference between the young and the adult groups after seven-day force application (p > 0.05), but it was significantly higher in the adult group than that in the young group after seven-day post-orthodontic retention (p < 0.05). Similarly, the decreasing trend of TRAP-positive osteoclasts during the retention period in the adult group was less obvious than that in the young group. Conclusions. The bone-resorptive activity in the young rats was more dynamic than that in the adult rats. The expression of RANKL and the number of osteoclasts in adult rats did not drop to the control level during the post-orthodontic retention period while RANKL expression and the number of osteoclasts in young rats had returned to the baseline. Cite this article: X. Li, M. Li, J. Lu, Y. Hu, L. Cui, D. Zhang, Y. Yang. Age-related effects on osteoclastic activities after orthodontic tooth movement. Bone Joint Res 2016;5:492–499. DOI: 10.1302/2046-3758.510.BJR-2016-0004.R2


Bone & Joint Research
Vol. 1, Issue 2 | Pages 13 - 19
1 Feb 2012
Smith MD Baldassarri S Anez-Bustillos L Tseng A Entezari V Zurakowski D Snyder BD Nazarian A

Objectives. This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone. Methods. A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity. Results. The average structural rigidity-based axial rigidity was well correlated with the average mechanically-derived axial rigidity results (R. 2. = 0.74). This correlation improved significantly (p < 0.0001) when the CT-based Structural Rigidity Analysis (CTRA) minimum axial rigidity was correlated to the mechanically-derived minimum axial rigidity results (R. 2. = 0.84). Tests of slopes in the mixed model regression analysis indicated a significantly steeper slope for the average axial rigidity compared with the minimum axial rigidity (p = 0.028) and a significant difference in the intercepts (p = 0.022). The CTRA average and minimum axial rigidities were correlated with the mechanically-derived average and minimum axial rigidities using paired t-test analysis (p = 0.37 and p = 0.18, respectively). Conclusions. In summary, the results of this study suggest that structural rigidity analysis of micro-CT data can be used to accurately and quantitatively measure the axial rigidity of bones with metabolic pathologies in an experimental rat model. It appears that minimum axial rigidity is a better model for measuring bone rigidity than average axial rigidity


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1670 - 1674
1 Dec 2006
Rogers BA Murphy CL Cannon SR Briggs TWR

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage. Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test. Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02). We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 8 | Pages 1199 - 1204
1 Nov 2002
Race A Miller MA Ayers DC Cleary RJ Mann KA

We have compared the interface morphology at the stem-cement interface of standard Charnley stems with a satin finish (Ra = 0.75 μm) with identical stems which had been grit-blasted over their proximal third (Ra = 5.3 μm) to promote a proximal bond. The stems were cemented into cadaver femora using conventional contemporary cementing techniques. After transverse sectioning, we determined the percentage of the perimeter of the stem which had a gap at the interface. There were substantial gaps (mean 31.4 ± 17.1%) at the stem-cement interface in the grit-blasted region. This fraction was significantly (paired t-test, p = 0.0054) higher than that found around the contralateral satin-finished stems (mean 7.7 ± 11.7%). Although studies of isolated metal-cement interfaces have shown that the bond strength can increase with surface roughness it cannot be assumed that this effect will be observed under clinical conditions


Bone & Joint Research
Vol. 7, Issue 8 | Pages 511 - 516
1 Aug 2018
Beverly M Mellon S Kennedy JA Murray DW

Objectives

We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.

Materials and Methods

Needles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 494 - 500
1 Jul 2018
Jiang L Zhu X Rong J Xing B Wang S Liu A Chu M Huang G

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Methods

We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 414 - 421
1 Jun 2018
Yu CD Miao WH Zhang YY Zou MJ Yan XF

Objectives

The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy.

Methods

Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 157 - 165
1 Feb 2018
Sun Y Kiraly AJ Sun AR Cox M Mauerhan DR Hanley EN

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).

Methods

Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 343 - 350
1 May 2018
He A Ning Y Wen Y Cai Y Xu K Cai Y Han J Liu L Du Y Liang X Li P Fan Q Hao J Wang X Guo X Ma T Zhang F

Aim

Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.

Patients and Methods

Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).


Bone & Joint Research
Vol. 6, Issue 8 | Pages 499 - 505
1 Aug 2017
Morrison RJM Tsang B Fishley W Harper I Joseph JC Reed MR

Objectives

We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change.

Methods

We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 259 - 269
1 May 2017
McKirdy A Imbuldeniya AM

Objectives

To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA).

Methods

This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s t-tests were used for direct comparison, whilst segmented regression was employed for projection analysis.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 252 - 262
1 Mar 2018
Nishida K Matsushita T Takayama K Tanaka T Miyaji N Ibaraki K Araki D Kanzaki N Matsumoto T Kuroda R

Objectives

This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model.

Methods

Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).


Bone & Joint Research
Vol. 6, Issue 11 | Pages 631 - 639
1 Nov 2017
Blyth MJG Anthony I Rowe P Banger MS MacLean A Jones B

Objectives

This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group.

Methods

A total of 139 patients were recruited from a single centre. Patients were randomised to receive either a manual UKA implanted with the aid of traditional surgical jigs, or a UKA implanted with the aid of a tactile guided robotic arm-assisted system. Outcome measures included the American Knee Society Score (AKSS), Oxford Knee Score (OKS), Forgotten Joint Score, Hospital Anxiety Depression Scale, University of California at Los Angeles (UCLA) activity scale, Short Form-12, Pain Catastrophising Scale, somatic disease (Primary Care Evaluation of Mental Disorders Score), Pain visual analogue scale, analgesic use, patient satisfaction, complications relating to surgery, 90-day pain diaries and the requirement for revision surgery.


Bone & Joint Research
Vol. 6, Issue 9 | Pages 566 - 571
1 Sep 2017
Cheng T Zhang X Hu J Li B Wang Q

Objectives

Surgeons face a substantial risk of infection because of the occupational exposure to blood-borne pathogens (BBPs) from patients undergoing high-risk orthopaedic procedures. This study aimed to determine the seroprevalence of four BBPs among patients undergoing joint arthroplasty in Shanghai, China. In addition, we evaluated the significance of pre-operative screening by calculating a cost-to-benefit ratio.

Methods

A retrospective observational study of pre-operative screening for BBPs, including hepatitis B and C viruses (HBV and HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP), was conducted for sequential patients in the orthopaedic department of a large urban teaching hospital between 01 January 2009 and 30 May 2016. Medical records were analysed to verify the seroprevalence of these BBPs among the patients stratified by age, gender, local origin, type of surgery, history of previous transfusion and marital status.


Bone & Joint Research
Vol. 6, Issue 8 | Pages 481 - 488
1 Aug 2017
Caruso G Bonomo M Valpiani G Salvatori G Gildone A Lorusso V Massari L

Objectives

Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years.

Methods

A total of 571 patients were included in this study, which analysed the incidence of cut-out in relation to several clinical variables: age; gender; the AO Foundation and Orthopaedic Trauma Association classification system (AO/OTA); type of nail; cervical-diaphyseal angle; surgical wait times; anti-osteoporotic medication; complete post-operative weight bearing; and radiological parameters (namely the lag-screw position with respect to the femoral head, the Cleveland system, the tip-apex distance (TAD), and the calcar-referenced tip-apex distance (CalTAD)).


Bone & Joint Research
Vol. 6, Issue 8 | Pages 514 - 521
1 Aug 2017
Mannering N Young T Spelman T Choong PF

Objectives

Whilst gait speed is variable between healthy and injured adults, the extent to which speed alone alters the 3D in vivo knee kinematics has not been fully described. The purpose of this prospective study was to understand better the spatiotemporal and 3D knee kinematic changes induced by slow compared with normal self-selected walking speeds within young healthy adults.

Methods

A total of 26 men and 25 women (18 to 35 years old) participated in this study. Participants walked on a treadmill with the KneeKG system at a slow imposed speed (2 km/hr) for three trials, then at a self-selected comfortable walking speed for another three trials. Paired t-tests, Wilcoxon signed-rank tests, Mann-Whitney U tests and Spearman’s rank correlation coefficients were conducted using Stata/IC 14 to compare kinematics of slow versus self-selected walking speed.


Bone & Joint Research
Vol. 6, Issue 8 | Pages 489 - 498
1 Aug 2017
Mifuji K Ishikawa M Kamei N Tanaka R Arita K Mizuno H Asahara T Adachi N Ochi M

Objectives

The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing.

Methods

Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 439 - 445
1 Jul 2017
Sekimoto T Ishii M Emi M Kurogi S Funamoto T Yonezawa Y Tajima T Sakamoto T Hamada H Chosa E

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Methods

Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent’s region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher’s exact probability test, Pearson’s correlation test, and Student’s t-test).


Bone & Joint Research
Vol. 6, Issue 6 | Pages 358 - 365
1 Jun 2017
Sanghani-Kerai A Coathup M Samazideh S Kalia P Silvio LD Idowu B Blunn G

Objectives

Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration.

Methods

MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 331 - 336
1 May 2017
Yamauchi R Itabashi T Wada K Tanaka T Kumagai G Ishibashi Y

Objectives

Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants.

Methods

Ti and Ti6Al4V implants were treated with UV light, and the chemical composition and contact angle on the surfaces were evaluated to confirm photofunctionalisation. The implants were inserted into femurs in rats, and the rats were killed two or four weeks after the surgery. For histomorphometric analysis, both the bone–implant contact (BIC) ratio and the bone volume (BV) ratio were calculated from histological analysis and microcomputed tomography data.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 500 - 511
1 Oct 2016
Raina DB Gupta A Petersen MM Hettwer W McNally M Tägil M Zheng M Kumar A Lidgren L

Objectives

We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

Materials and Methods

We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 253 - 258
1 Apr 2017
Hsu C Lin C Jou I Wang P Lee J

Objectives

Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats.

Methods

Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot


Bone & Joint Research
Vol. 6, Issue 3 | Pages 154 - 161
1 Mar 2017
Liu J Li X Zhang H Gu R Wang Z Gao Z Xing L

Objectives

Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown.

Methods

We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 82 - 89
1 Feb 2017
Nagra NS Zargar N Smith RDJ Carr AJ

Objectives

All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors.

Materials and Methods

A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05.


Bone & Joint Research
Vol. 5, Issue 2 | Pages 26 - 32
1 Feb 2016
Wendling A Mar D Wischmeier N Anderson D McIff T

Objectives

The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength.

Methods

Three batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priorit-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 577 - 585
1 Nov 2016
Hase E Sato K Yonekura D Minamikawa T Takahashi M Yasui T

Objectives

This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing.

Materials and Methods

A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation.


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.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 523 - 530
1 Oct 2016
Yuan Y Zhang GQ Chai W Ni M Xu C Chen JY

Objectives

Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.

Materials and Methods

Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 412 - 418
1 Sep 2016
Ye S Ju B Wang H Lee K

Objectives

Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration.

Methods

Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 403 - 411
1 Sep 2016
Mrosek EH Chung H Fitzsimmons JS O’Driscoll SW Reinholz GG Schagemann JC

Objectives

We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling.

Materials and Methods

Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Methods

Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 218 - 224
1 Jun 2016
Cheng N Guo A Cui Y

Objectives

Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA.

Methods

Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.


Bone & Joint Research
Vol. 5, Issue 1 | Pages 1 - 10
1 Jan 2016
Burghardt RD Manzotti A Bhave A Paley D Herzenberg JE

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Methods

In this matched case study, 16 adult patients underwent 19 tibial lengthening over nails (LON) procedures. For the matched case group, 17 patients who underwent 19 Ilizarov tibial lengthenings were retrospectively matched to the LON group.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 862 - 868
1 Jun 2015
Corominas-Frances L Sanpera I Saus-Sarrias C Tejada-Gavela S Sanpera-Iglesias J Frontera-Juan G

Rebound growth after hemiepiphysiodesis may be a normal event, but little is known about its causes, incidence or factors related to its intensity. The aim of this study was to evaluate rebound growth under controlled experimental conditions.

A total of 22 six-week-old rabbits underwent a medial proximal tibial hemiepiphysiodesis using a two-hole plate and screws. Temporal growth plate arrest was maintained for three weeks, and animals were killed at intervals ranging between three days and three weeks after removal of the device. The radiological angulation of the proximal tibia was studied at weekly intervals during and after hemiepiphysiodesis. A histological study of the retrieved proximal physis of the tibia was performed.

The mean angulation achieved at three weeks was 34.7° (standard deviation (sd) 3.4), and this remained unchanged for the study period of up to two weeks. By three weeks after removal of the implant the mean angulation had dropped to 28.2° (sd 1.8) (p < 0.001). Histologically, widening of the medial side was noted during the first two weeks. By three weeks this widening had substantially disappeared and the normal columnar structure was virtually re-established.

In our rabbit model, rebound was an event of variable incidence and intensity and, when present, did not appear immediately after restoration of growth, but took some time to appear.

Cite this article: Bone Joint J 2015;97-B:862–8.


Bone & Joint Research
Vol. 4, Issue 5 | Pages 78 - 83
1 May 2015
Martinkevich P Rahbek O Møller-Madsen B Søballe K Stilling M

Objectives

Lengthening osteotomies of the calcaneus in children are in general grafted with bone from the iliac crest. Artificial bone grafts have been introduced, however, their structural and clinical durability has not been documented. Radiostereometric analysis (RSA) is a very accurate and precise method for measurements of rigid body movements including the evaluation of joint implant and fracture stability, however, RSA has not previously been used in clinical studies of calcaneal osteotomies. We assessed the precision of RSA as a measurement tool in a lateral calcaneal lengthening osteotomy (LCLO).

Methods

LCLO was performed in six fixed adult cadaver feet. Tantalum markers were inserted on each side of the osteotomy and in the cuboideum. Lengthening was done with a plexiglas wedge. A total of 24 radiological double examinations were obtained. Two feet were excluded due to loose and poorly dispersed markers. Precision was assessed as systematic bias and 95% repeatability limits.


Bone & Joint Research
Vol. 3, Issue 9 | Pages 273 - 279
1 Sep 2014
Vasiliadis ES Kaspiris A Grivas TB Khaldi L Lamprou M Pneumaticos SG Nikolopoulos K Korres DS Papadimitriou E

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

Methods

A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 998 - 1006
1 Jul 2012
Kodama A Kamei N Kamei G Kongcharoensombat W Ohkawa S Nakabayashi A Ochi M

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.


Bone & Joint Research
Vol. 2, Issue 9 | Pages 179 - 185
1 Sep 2013
Warwick DJ Shaikh A Gadola S Stokes M Worsley P Bain D Tucker AT Gadola SD

Objectives

We aimed to examine the characteristics of deep venous flow in the leg in a cast and the effects of a wearable neuromuscular stimulator (geko; FirstKind Ltd) and also to explore the participants’ tolerance of the stimulator.

Methods

This is an open-label physiological study on ten healthy volunteers. Duplex ultrasonography of the superficial femoral vein measured normal flow and cross-sectional area in the standing and supine positions (with the lower limb initially horizontal and then elevated). Flow measurements were repeated during activation of the geko stimulator placed over the peroneal nerve. The process was repeated after the application of a below-knee cast. Participants evaluated discomfort using a questionnaire (verbal rating score) and a scoring index (visual analogue scale).


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1249 - 1255
1 Sep 2008
Nishida H Tsuchiya H Tomita K

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured.

Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 41 - 50
1 Feb 2013
Cottrell JA Keshav V Mitchell A O’Connor JP

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Methods

Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 691 - 699
1 May 2009
Amin AK Huntley JS Simpson AHRW Hall AC

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture.

The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1176 - 1181
1 Aug 2010
Tayton E Evans S O’Doherty D

We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral prostheses of the same dimensions into five prosthetic femora. An abductor jig was attached and a 1 kN load applied. This was repeated with five control femora. Digital image correlation was used to give a detailed two-dimensional strain map of the medial cortex of the proximal femur. Both implants caused stress shielding around the calcar. Distally, the titanium implant showed stress shielding, whereas the CFRP prosthesis did not produce a strain pattern which was statistically different from the controls. There was a reduction in strain beyond the tip of both the implants.

This investigation indicates that use of the CFRP stem should avoid stress shielding in total hip replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 520 - 526
1 Apr 2008
Yau WP Leung A Liu KG Yan CH Wong LS Chiu KY

We have investigated the errors in the identification of the transepicondylar axis and the anteroposterior axis between a minimally-invasive and a conventional approach in four fresh-frozen cadaver knees. The errors in aligning the femoral prosthesis were compared with the reference transepicondylar axis as established by CT.

The error in the identification of the transepicondylar axis was significantly higher in the minimal approach (4.5° of internal rotation, sd 4) than in the conventional approach (3° of internal rotation, sd 4; p < 0.001). The errors in identifying the anteroposterior axis in the two approaches were 0° (sd 5) and 1.8° (sd 5) of internal rotation, respectively (p < 0.001).


Bone & Joint Research
Vol. 1, Issue 7 | Pages 145 - 151
1 Jul 2012
Sharma A Meyer F Hyvonen M Best SM Cameron RE Rushton N

Objectives

There is increasing application of bone morphogenetic proteins (BMPs) owing to their role in promoting fracture healing and bone fusion. However, an optimal delivery system has yet to be identified. The aims of this study were to synthesise bioactive BMP-2, combine it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide) (α-TCP/PLGA) nanocomposite and study its release from the composite.

Methods

BMP-2 was synthesised using an Escherichia coli expression system and purified. In vitro bioactivity was confirmed using C2C12 cells and an alkaline phosphatase assay. The modified solution-evaporation method was used to fabricate α-TCP/PLGA nanocomposite and this was characterised using X-ray diffraction and scanning electron microscopy. Functionalisation of α-TCP/PLGA nanocomposite by adsorption of BMP-2 was performed and release of BMP-2 was characterised using an enzyme-linked immunosorbent assay (ELISA).


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 5 | Pages 680 - 684
1 May 2008
Simon DWN Clarkin CE Das-Gupta V Rawlinson SCF Emery RJ Pitsillides AA

We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff.

We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity.

Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 277 - 284
1 Feb 2011
Amin AK Huntley JS Patton JT Brenkel IJ Simpson AHRW Hall AC

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury.

Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline.

These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 119 - 123
1 Jan 2009
Benson RT McDonnell SM Rees JL Athanasou NA Carr AJ

We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts.

At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1171 - 1175
1 Aug 2010
Hajipour L Gulihar A Dias J

We carried out lacerations of 50%, followed by trimming, in ten turkey flexor tendons in vitro and measured the coefficient of friction at the tendon-pulley interface with loads of 200 g and 400 g and in 10°, 30°, 50° and 70° of flexion. Laceration increased the coefficient of friction from 0.12 for the intact tendon to 0.3 at both the test loads. Trimming the laceration reduced the coefficient of friction to 0.2. An exponential increase in the gliding resistance was found at 50° and 70° of flexion (p = 0.02 and p = 0.003, respectively) following trimming compared to that of the intact tendon.

We concluded that trimming partially lacerated flexor tendons will reduce the gliding resistance at the tendon-pulley interface, but will lead to fragmentation and triggering of the tendon at higher degrees of flexion and loading. We recommend that higher degrees of flexion be avoided during early post-operative rehabilitation following trimming of a flexor tendon.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1033 - 1040
1 Jul 2010
Nishino T Chang F Ishii T Yanai T Mishima H Ochiai N

We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1261 - 1267
1 Sep 2007
Tohyama H Yasuda K Uchida H Nishihira J

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon.

Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1β than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1β was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-β1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1β had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 103 - 106
1 Jan 2008
Kettler M Tingart MJ Lunger J Kuhn V

Operative fixation is the treatment of choice for a rupture of the distal tendon of biceps. A variety of techniques have been described including transosseous sutures and suture anchors. The poor quality of the bone of the radial tuberosity might affect the load to failure of the tendon repair in early rehabilitation.

The aim of this study was to determine the loads to failure of different techniques of fixation and to investigate their association with the bone mineral density of the radial tuberosity.

Peripheral quantitative computed tomography was carried out to measure the trabecular and cortical bone mineral density of the radial tuberosity in 40 cadaver specimens. The loads to failure in four different techniques of fixation were determined.

The Endobutton-based method showed the highest failure load at 270 N (sd 22) (p < 0.05). The mean failure load of the transosseous suture technique was 210 N (sd 66) and that of the TwinFix-QuickT 5.0 mm was 57 N (sd 22), significantly lower than those of all other repairs (p < 0.05). No significant correlation was seen between bone mineral density and loads to failure.

The transosseous technique is an easy and cost-saving procedure for fixation of the distal biceps tendon. TwinFix-QuickT 5.0 mm had significantly lower failure loads, which might affect early rehabilitation, particularly in older patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 107 - 113
1 Jan 2008
Scheerlinck T Vandenbussche P Noble PC

Interfacial defects between the cement mantle and a hip implant may arise from constrained shrinkage of the cement or from air introduced during insertion of the stem. Shrinkage-induced interfacial porosity consists of small pores randomly located around the stem, whereas introduced interfacial gaps are large, individual and less uniformly distributed areas of stem-cement separation. Using a validated CT-based technique, we investigated the extent, morphology and distribution of interfacial gaps for two types of stem, the Charnley-Kerboul and the Lubinus SPII, and for two techniques of implantation, line-to-line and undersized.

The interfacial gaps were variable and involved a mean of 6.43% (sd 8.99) of the surface of the stem. Neither the type of implant nor the technique of implantation had a significant effect on the regions of the gaps, which occurred more often over the flat areas of the implant than along the corners of the stems, and were more common proximally than distally for Charnley-Kerboul stems cemented line-to-line. Interfacial defects could have a major effect on the stability and survival of the implant.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 3 | Pages 461 - 467
1 Mar 2010
Wik TS Østbyhaug PO Klaksvik J Aamodt A

The cortical strains on the femoral neck and proximal femur were measured before and after implantation of a resurfacing femoral component in 13 femurs from human cadavers. These were loaded into a hip simulator for single-leg stance and stair-climbing. After resurfacing, the mean tensile strain increased by 15% (95% confidence interval (CI) 6 to 24, p = 0.003) on the lateral femoral neck and the mean compressive strain increased by 11% (95% CI 5 to 17, p = 0.002) on the medial femoral neck during stimulation of single-leg stance. On the proximal femur the deformation pattern remained similar to that of the unoperated femurs.

The small increase of strains in the neck area alone would probably not be sufficient to cause fracture of the neck However, with patient-related and surgical factors these strain changes may contribute to the risk of early periprosthetic fracture.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 320 - 325
1 Feb 2010
Wang G Yang H Li M Lu S Chen X Cai X

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study.

The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 131 - 137
1 Jan 2009
Boraiah S Dyke JP Hettrich C Parker RJ Miller A Helfet D Lorich D

In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 558 - 565
1 Apr 2011
Xie X Wang X Zhang G Liu Z Yao D Hung L Hung VW Qin L

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis.

In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.

We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 557 - 564
1 Apr 2009
Rumian AP Draper ERC Wallace AL Goodship AE

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons.

The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1471 - 1474
1 Oct 2010
Chang Y Shih H Chen DW Lee MS Ueng SWN Hsieh P

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria.

We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1703 - 1709
1 Dec 2010
Aoki H Nagao Y Ishii S Masuda T Beppu M

In order to evaluate the relationship between acetabular and proximal femoral alignment in the initiation and evolution of osteoarthritis of the dysplastic hip, the acetabular and femoral angles were calculated geometrically from radiographs of 62 patients with pre-arthrosis and early osteoarthritis. The sum of the lateral opening angle of the acetabulum and the neck-shaft angle was defined as the lateral instability index (LII), and the sum of the anterior opening angle of the acetabulum and the anteversion angle of the femoral neck as the anterior instability index (AII). These two indices were compared in dysplastic and unaffected hips. A total of 22 unilateral hips with pre-arthrosis were followed for at least 15 years to determine whether the two indices were associated with the progression of osteoarthritis.

The LII of the affected hips (197.4 (sd 6.0)) was significantly greater than that of the unaffected hips (1830 (sd 6.9)). A follow-up study of 22 hips with pre-arthrosis showed that only the LII was associated with progression of the disease, and an LII of 196 was the threshold value for this progression.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 6 | Pages 823 - 827
1 Jun 2006
White TO Clutton RE Salter D Swann D Christie J Robinson CM

The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’).

Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 11 | Pages 1614 - 1620
1 Nov 2010
Fini M Tschon M Ronchetti M Cavani F Bianchi G Mercuri M Alberghini M Cadossi R

Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells.

Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing.

After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times.

Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1041 - 1044
1 Jul 2010
Loughenbury PR Harwood PJ Tunstall R Britten S

Anatomical atlases document safe corridors for placement of wires when using fine-wire circular external fixation. The furthest posterolateral corridor described in the distal tibia is through the fibula. This limits the crossing angle and stability of the frame. In this paper we describe a new, safe Retro-Fibular Wire corridor, which provides greater crossing angles and increased stability. In a cadaver study, 20 formalin-treated legs were divided into two groups. Wires were inserted into the distal quarter of the tibia using two possible corridors and standard techniques of dissection identified the distance of the wires from neurovascular structures.

In both groups the posterior tibial neurovascular bundle was avoided. In group A the peroneal artery was at risk. In group B this injury was avoided. Comparison of the groups showed a significant difference (p < 0.001).

We recommend the Retro-Fibular wire technique whereby wires are inserted into the tibia mid-way between the posteromedial border of the fibula and the tendo Achillis, at 30° to 45° to the sagittal plane, and introduced from a posterolateral to an anteromedial position. Subsequently, when using this technique in 30 patients, we have had no neurovascular complications or problems relating to tethering of the peroneal tendons.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 743 - 746
1 May 2010
Colegate-Stone T Allom R Singh R Elias DA Standring S Sinha J

The aim of this study was to establish a classification system for the acromioclavicular joint using cadaveric dissection and radiological analyses of both reformatted computed tomographic scans and conventional radiographs centred on the joint. This classification should be useful for planning arthroscopic procedures or introducing a needle and in prospective studies of biomechanical stresses across the joint which may be associated with the development of joint pathology.

We have demonstrated three main three-dimensional morphological groups namely flat, oblique and curved, on both cadaveric examination and radiological assessment. These groups were recognised in both the coronal and axial planes and were independent of age.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 889 - 893
1 Jun 2010
Kocaoglu B Agir I Nalbantoglu U Karahan M Türkmen M

We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups.

Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1292 - 1297
1 Sep 2005
Lietman SA Inoue N Rafiee B Deitz LW Chao EYS

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 595 - 601
1 Apr 2010
Kafchitsas K Kokkinakis M Habermann B Rauschmann M

In a study on ten fresh human cadavers we examined the change in the height of the intervertebral disc space, the angle of lordosis and the geometry of the facet joints after insertion of intervertebral total disc replacements. SB III Charité prostheses were inserted at L3-4, L4-5, and L5-S1. The changes studied were measured using computer navigation sofware applied to CT scans before and after instrumentation.

After disc replacement the mean lumbar disc height was doubled (p < 0.001). The mean angle of lordosis and the facet joint space increased by a statistically significant extent (p < 0.005 and p = 0.006, respectively). By contrast, the mean facet joint overlap was significantly reduced (p < 0.001). Our study indicates that the increase in the intervertebral disc height after disc replacement changes the geometry at the facet joints. This may have clinical relevance.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 164 - 168
1 Jan 2010
Chen MR Huang JI Victoroff BN Cooperman DR

In an osteological collection of 3100 specimens, 70 were found with unilateral clavicular fractures which were matched with 70 randomly selected normal specimens. This formed the basis of a study of the incidence of arthritis of the acromioclavicular joint and the effect of clavicular fracture on the development of arthritis in the ipsilateral acromioclavicular joint. This was graded visually on a severity scale of 0 to 3. The incidence of moderate to severe arthritis of the acromioclavicular joint in normal specimens was 77% (100 specimens). In those with a clavicular fracture, 66 of 70 (94%) had arthritis of the acromioclavicular joint, compared to 63 of 70 (90%) on the non-injured contralateral side (p = 0.35).

Clavicles with shortening of 15 mm or less had no difference in the incidence of arthritis compared to those with shortening greater than 15 mm (p = 0.25). The location of the fracture had no effect on the development of arthritis.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 298 - 303
1 Feb 2010
Toom A Suutre S Märtson A Haviko T Selstam G Arend A

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically.

Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (sd 4.5) versus 12.7% (sd 2.9, p < 0.019), respectively.

Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 3 | Pages 448 - 453
1 Mar 2010
Benson RT McDonnell SM Knowles HJ Rees JL Carr AJ Hulley PA

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 304 - 310
1 Feb 2010
Jia W Zhang C Wang J Feng Y Ai Z

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 7 | Pages 973 - 976
1 Jul 2009
Kralinger F Unger S Wambacher M Smekal V Schmoelz W

The medial periosteal hinge plays a key role in fractures of the head of the humerus, offering mechanical support during and after reduction and maintaining perfusion of the head by the vessels in the posteromedial periosteum. We have investigated the biomechanical properties of the medial periosteum in fractures of the proximal humerus using a standard model in 20 fresh-frozen cadaver specimens comparable in age, gender and bone mineral density. After creating the fracture, we displaced the humeral head medial or lateral to the shaft with controlled force until complete disruption of the posteromedial periosteum was recorded. As the quality of periosteum might be affected by age and bone quality, the results were correlated with the age and the local bone mineral density of the specimens measured with quantitative CT.

Periosteal rupture started at a mean displacement of 2.96 mm (sd 2.92) with a mean load of 100.9 N (sd 47.1). The mean maximum load of 111.4 N (sd 42.5) was reached at a mean displacement of 4.9 mm (sd 4.2). The periosteum was completely ruptured at a mean displacement of 34.4 mm (sd 11.1). There was no significant difference in the mean distance to complete rupture for medial (mean 35.8 mm (sd 13.8)) or lateral (mean 33.0 mm (sd 8.2)) displacement (p = 0.589).

The mean bone mineral density was 0.111 g/cm3 (sd 0.035). A statistically significant but low correlation between bone mineral density and the maximum load uptake (r = 0.475, p = 0.034) was observed.

This study showed that the posteromedial hinge is a mechanical structure capable of providing support for percutaneous reduction and stabilisation of a fracture by ligamentotaxis. Periosteal rupture started at a mean of about 3 mm and was completed by a mean displacement of just under 35 mm. The microvascular situation of the rupturing periosteum cannot be investigated with the current model.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 676 - 682
1 May 2009
Østbyhaug PO Klaksvik J Romundstad P Aamodt A

Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems.

Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or upper diaphyseal part of the proximal femur.

The customised stem induced a strain pattern more similar to that of the intact femur than the standard, anatomical stem.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 6 | Pages 868 - 872
1 Jun 2005
Metcalfe AJ Saleh M Yang L

Biomechanical studies involving all-wire and hybrid types of circular frame have shown that oblique tibial fractures remain unstable when they are loaded. We have assessed a range of techniques for enhancing the fixation of these fractures. Eight models were constructed using Sawbones tibiae and standard Sheffield ring fixators, to which six additional fixation techniques were applied sequentially.

The major component of displacement was shear along the obliquity of the fracture. This was the most sensitive to any change in the method of fixation. All additional fixation systems were found to reduce shear movement significantly, the most effective being push-pull wires and arched wires with a three-hole bend. Less effective systems included an additional half pin and arched wires with a shallower arc. Angled pins were more effective at reducing shear than transverse pins.

The choice of additional fixation should be made after consideration of both the amount of stability required and the practicalities of applying the method to a particular fracture.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1426 - 1433
1 Oct 2005
Kobayashi T Watanabe H Yanagawa T Tsutsumi S Kayakabe M Shinozaki T Higuchi H Takagishi K

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures.

Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 683 - 690
1 May 2009
Victor J Van Doninck D Labey L Van Glabbeek F Parizel P Bellemans J

The understanding of rotational alignment of the distal femur is essential in total knee replacement to ensure that there is correct placement of the femoral component. Many reference axes have been described, but there is still disagreement about their value and mutual angular relationship. Our aim was to validate a geometrically-defined reference axis against which the surface-derived axes could be compared in the axial plane. A total of 12 cadaver specimens underwent CT after rigid fixation of optical tracking devices to the femur and the tibia. Three-dimensional reconstructions were made to determine the anatomical surface points and geometrical references. The spatial relationships between the femur and tibia in full extension and in 90° of flexion were examined by an optical infrared tracking system.

After co-ordinate transformation of the described anatomical points and geometrical references, the projection of the relevant axes in the axial plane of the femur were mathematically achieved. Inter- and intra-observer variability in the three-dimensional CT reconstructions revealed angular errors ranging from 0.16° to 1.15° for all axes except for the trochlear axis which had an interobserver error of 2°. With the knees in full extension, the femoral transverse axis, connecting the centres of the best matching spheres of the femoral condyles, almost coincided with the tibial transverse axis (mean difference −0.8°, sd 2.05). At 90° of flexion, this femoral transverse axis was orthogonal to the tibial mechanical axis (mean difference −0.77°, sd 4.08). Of all the surface-derived axes, the surgical transepicondylar axis had the closest relationship to the femoral transverse axis after projection on to the axial plane of the femur (mean difference 0.21°, sd 1.77). The posterior condylar line was the most consistent axis (range −2.96° to −0.28°, sd 0.77) and the trochlear anteroposterior axis the least consistent axis (range −10.62° to +11.67°, sd 6.12). The orientation of both the posterior condylar line and the trochlear anteroposterior axis (p = 0.001) showed a trend towards internal rotation with valgus coronal alignment.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1635 - 1640
1 Dec 2008
Spence G Phillips S Campion C Brooks R Rushton N

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model.

Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively.

After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 6 | Pages 835 - 842
1 Jun 2009
Hart AJ Skinner JA Winship P Faria N Kulinskaya E Webster D Muirhead-Allwood S Aldam CH Anwar H Powell JJ

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders.

Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8+ lymphopenia) and 11 patients (13%) (CD3+ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8+ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 3 | Pages 417 - 424
1 Mar 2009
Millar NL Wei AQ Molloy TJ Bonar F Murrell GAC

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry.

We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008).

These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 11 | Pages 1522 - 1527
1 Nov 2008
Davis ET Olsen M Zdero R Waddell JP Schemitsch EH

A total of 20 pairs of fresh-frozen cadaver femurs were assigned to four alignment groups consisting of relative varus (10° and 20°) and relative valgus (10° and 20°), 75 composite femurs of two neck geometries were also used. In both the cadaver and the composite femurs, placing the component in 20° of valgus resulted in a significant increase in load to failure. Placing the component in 10° of valgus had no appreciable effect on increasing the load to failure except in the composite femurs with varus native femoral necks. Specimens in 10° of varus were significantly weaker than the neutrally-aligned specimens.

The results suggest that retention of the intact proximal femoral strength occurs at an implant angulation of ≥ 142°. However, the benefit of extreme valgus alignment may be outweighed in clinical practice by the risk of superior femoral neck notching, which was avoided in this study.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 120 - 127
1 Jan 2005
Skurla CP Pluhar GE Frankel DJ Egger EL James SP

Post-mortem retrieval of canine, cemented femoral components was analysed to assess the performance of these implants in the dog as a model for human total hip replacement (THR). Mechanical testing and radiological analysis were performed to determine the stability of the implant and the quality of the cement. Thirty-eight implants from 29 dogs were retrieved after time intervals ranging from 0.67 to 11.67 years. The incidence of aseptic loosening was 63.2%, much higher than in human patients (6% in post-mortem studies). Failure of the femoral implants began with debonding at the cement-metal interface, similar to that in implants in man. The incidence of aseptic loosening was much lower in bilateral than in unilateral implants. Significant differences were observed for three different designs of implant. While the dog remains the animal model of choice for THR, results from this study provide insight into interspecies differences in the performance of implants. For example, the performance of THR in dogs should be compared with that in young rather than in elderly human patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 6 | Pages 836 - 838
1 Jun 2007
Grechenig W Clement H Pichler W Tesch NP Windisch G

We have investigated the anatomy of the proximal part of the ulna to assess its influence on the use of plates in the management of fractures at this site. We examined 54 specimens from cadavers. The mean varus angulation in the proximal third was 17.5° (11° to 23°) and the mean anterior deviation 4.5° (1° to 14°). These variations must be considered when applying plates to the dorsal surface of the ulna for Monteggia-type fractures. A pre-operative radiograph of the contralateral elbow may also be of value.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 3 | Pages 388 - 392
1 Mar 2008
Virchenko O Aspenberg P Lindahl TL

Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair.

Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed.

Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections.

Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 6 | Pages 814 - 820
1 Jun 2008
Chu CR Izzo NJ Coyle CH Papas NE Logar A

We have studied the effects of bupivacaine on human and bovine articular chondrocytes in vitro. Time-lapse confocal microscopy of human articular chondrocytes showed > 95% cellular death after exposure to 0.5% bupivacaine for 30 minutes. Human and bovine chondrocytes exposed to 0.25% bupivacaine had a time-dependent reduction in viability, with longer exposure times resulting in higher cytotoxicity. Cellular death continued even after removal of 0.25% bupivacaine. After exposure to 0.25% bupivacaine for 15 minutes, flow cytometry showed bovine chondrocyte viability to be 41% of saline control after seven days. After exposure to 0.125% bupivacaine for up to 60 minutes, the viability of both bovine and human chondrocytes was similar to that of control groups.

These data show that prolonged exposure 0.5% and 0.25% bupivacaine solutions are potentially chondrotoxic.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 4 | Pages 557 - 560
1 Apr 2007
Davis ET Gallie P Macgroarty K Waddell JP Schemitsch E

A cadaver study using six pairs of lower limbs was conducted to investigate the accuracy of computer navigation and standard instrumentation for the placement of the Birmingham Hip Resurfacing femoral component. The aim was to place all the femoral components with a stem-shaft angle of 135°.

The mean stem-shaft angle obtained in the standard instrumentation group was 127.7° (120° to 132°), compared with 133.3° (131° to 139°) in the computer navigation group (p = 0.03). The scatter obtained with computer-assisted navigation was approximately half that found using the conventional jig.

Computer navigation was more accurate and more consistent in its placement of the femoral component than standard instrumentation. We suggest that image-free computer-assisted navigation may have an application in aligning the femoral component during hip resurfacing.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1666 - 1672
1 Dec 2007
Mizuno S Takebayashi T Kirita T Tanimoto K Tohse N Yamashita T

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation.

On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 μm to 10 μm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia.

The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly.

We consider that the sympathetic nervous system plays an important role in the generation of radicular pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 6 | Pages 830 - 835
1 Jun 2007
Hara Y Ochiai N Abe I Ichimura H Saijilafu Nishiura Y

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal.

Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 413 - 416
1 Mar 2007
van Riet RP van Glabbeek F de Weerdt W Oemar J Bortier H

We undertook a study on eight arms from fresh cadavers to define the clinical usefulness of the lesser sigmoid notch as a landmark when reconstructing the length of the neck of the radius in replacement of the head with a prosthesis. The head was resected and its height measured, along with several control measurements. This was compared with in situ measurements from the stump of the neck to the proximal edge of the lesser sigmoid notch of the ulna. All the measurements were performed three times by three observers acting independently.

The results were highly reproducible with intra- and interclass correlations of > 0.99. The mean difference between the measurement on the excised head and the distance from the stump of the neck and the lesser sigmoid notch was −0.02 mm (−1.24 to +0.97). This difference was not statistically significant (p = 0.78).

The proximal edge of the lesser sigmoid notch provides a reliable landmark for positioning a replacement of the radial head and may have clinical application.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 408 - 412
1 Mar 2007
Ma H Lu Y Kwok T Ho F Huang C Huang C

One of the most controversial issues in total knee replacement is whether or not to resurface the patella. In order to determine the effects of different designs of femoral component on the conformity of the patellofemoral joint, five different knee prostheses were investigated. These were Low Contact Stress, the Miller-Galante II, the NexGen, the Porous-Coated Anatomic, and the Total Condylar prostheses. Three-dimensional models of the prostheses and a native patella were developed and assessed by computer. The conformity of the curvature of the five different prosthetic femoral components to their corresponding patellar implants and to the native patella at different angles of flexion was assessed by measuring the angles of intersection of tangential lines.

The Total Condylar prosthesis had the lowest conformity with the native patella (mean 8.58°; 0.14° to 29.9°) and with its own patellar component (mean 11.36°; 0.55° to 39.19°). In the other four prostheses, the conformity was better (mean 2.25°; 0.02° to 10.52°) when articulated with the corresponding patellar component. The Porous-Coated Anatomic femoral component showed better conformity (mean 6.51°; 0.07° to 9.89°) than the Miller-Galante II prosthesis (mean 11.20°; 5.80° to 16.72°) when tested with the native patella. Although the Nexgen prosthesis had less conformity with the native patella at a low angle of flexion, this improved at mid (mean 3.57°; 1.40° to 4.56°) or high angles of flexion (mean 4.54°; 0.91° to 9.39°), respectively. The Low Contact Stress femoral component had the best conformity with the native patella (mean 2.39°; 0.04° to 4.56°). There was no significant difference (p > 0.208) between the conformity when tested with the native patella or its own patellar component at any angle of flexion.

The geometry of the anterior flange of a femoral component affects the conformity of the patellofemoral joint when articulating with the native patella. A more anatomical design of femoral component is preferable if the surgeon decides not to resurface the patella at the time of operation.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 133 - 138
1 Jan 2007
Oe K Miwa M Sakai Y Lee SY Kuroda R Kurosaka M

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 127 - 129
1 Jan 2007
Tang TT Lu B Yue B Xie XH Xie YZ Dai KR Lu JX Lou JR

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 686 - 692
1 May 2007
Bolland BJRF New AMR Madabhushi SPG Oreffo ROC Dunlop DG

The complications of impaction bone grafting in revision hip replacement includes fracture of the femur and subsidence of the prosthesis. In this in vitro study we aimed to investigate whether the use of vibration, combined with a perforated tamp during the compaction of morsellised allograft would reduce peak loads and hoop strains in the femur as a surrogate marker of the risk of fracture and whether it would also improve graft compaction and prosthetic stability.

We found that the peak loads and hoop strains transmitted to the femoral cortex during graft compaction and subsidence of the stem in subsequent mechanical testing were reduced. This innovative technique has the potential to reduce the risk of intra-operative fracture and to improve graft compaction and therefore prosthetic stability.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 5 | Pages 692 - 695
1 May 2006
Karataglis D Kapetanos G Lontos A Christodoulou A Christoforides J Pournaras J

The aim of this biomechanical study was to investigate the role of the dorsal vertebral cortex in transpedicular screw fixation. Moss transpedicular screws were introduced into both pedicles of each vertebra in 25 human cadaver vertebrae. The dorsal vertebral cortex and subcortical bone corresponding to the entrance site of the screw were removed on one side and preserved on the other. Biomechanical testing showed that the mean peak pull-out strength for the inserted screws, following removal of the dorsal cortex, was 956.16 N. If the dorsal cortex was preserved, the mean peak pullout strength was 1295.64 N. The mean increase was 339.48 N (26.13%; p = 0.033). The bone mineral density correlated positively with peak pull-out strength.

Preservation of the dorsal vertebral cortex at the site of insertion of the screw offers a significant increase in peak pull-out strength. This may result from engagement by the final screw threads in the denser bone of the dorsal cortex and the underlying subcortical area. Every effort should be made to preserve the dorsal vertebral cortex during insertion of transpedicular screws.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 258 - 264
1 Feb 2007
Nagura I Fujioka H Kokubu T Makino T Sumi Y Kurosaka M

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group.

Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p < 0.05).

Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1105 - 1109
1 Aug 2006
Kandemir U Allaire RB Jolly JT Debski RE McMahon PJ

Our aim was to determine the most repeatable three-dimensional measurement of glenoid orientation and to compare it between shoulders with intact and torn rotator cuffs. Our null hypothesis was that glenoid orientation in the scapulae of shoulders with a full-thickness tear of the rotator cuff was the same as that in shoulders with an intact rotator cuff.

We studied 24 shoulders in cadavers, 12 with an intact rotator cuff and 12 with a full-thickness tear. Two different observers used a three-dimensional digitising system to measure glenoid orientation in the scapular plane (ie glenoid inclination) using six different techniques. Glenoid version was also measured. The overall precision of the measurements revealed an error of less than 0.6°.

Intraobserver reliability (correlation coefficients of 0.990 and 0.984 for each observer) and interobserver reliability (correlation coefficient of 0.985) were highest for measurement of glenoid inclination based on the angle obtained from a line connecting the superior and inferior points of the glenoid and that connecting the most superior point of the glenoid and the most superior point on the body of the scapula. There were no differences in glenoid inclination (p = 0.34) or glenoid version (p = 0.12) in scapulae from shoulders with an intact rotator cuff and those with a full-thickness tear. Abnormal glenoid orientation was not present in shoulders with a torn rotator cuff.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1394 - 1400
1 Oct 2006
Eid K Labler L Ertel W Trentz O Keel M

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects.

The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031).

Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 129 - 133
1 Jan 2006
Lee SY Miwa M Sakai Y Kuroda R Niikura T Kurosaka M

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with β-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)2D3, a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced.

Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 741 - 744
1 May 2005
Beaulé PE Krismer M Mayrhofer P Wanner S Le Duff M Mattesich M Stoeckl B Amstutz HC Biedermann R

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse - femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers.

The accuracy of the method was found to be ± 1.6 mm for the x-direction and ± 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively.

EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.