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The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 144 - 147
1 Jan 2001
Mayr-Wohlfart U Kessler S Puhl W Günther KP Knöchel W

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 3 | Pages 426 - 432
1 Mar 2005
Mueller CA Eingartner C Schreitmueller E Rupp S Goldhahn J Schuler F Weise K Pfister U Suedkamp NP

The treatment of fractures of the proximal tibia is complex and makes great demands on the implants used. Our study aimed to identify what levels of primary stability could be achieved with various forms of osteosynthesis in the treatment of diaphyseal fractures of the proximal tibia. Pairs of human tibiae were investigated. An unstable fracture was simulated by creating a defect at the metaphyseal-diaphyseal junction. Six implants were tested in a uniaxial testing device (Instron) using the quasi-static and displacement-controlled modes and the force-displacement curve was recorded. The movements of each fragment and of the implant were recorded video-optically (MacReflex, Qualysis). Axial deviations were evaluated at 300 N. The results show that the nailing systems tolerated the highest forces. The lowest axial deviations in varus and valgus were also found for the nailing systems; the highest axial deviations were recorded for the buttress plate and the less invasive stabilising system (LISS). In terms of rotational displacement the LISS was better than the buttress plate. In summary, it was found that higher loads were better tolerated by centrally placed load carriers than by eccentrically placed ones. In the case of the latter, it appears advantageous to use additive procedures for medial buttressing in the early phase


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 2 | Pages 278 - 282
1 Mar 2001
Wimhurst JA Brooks RA Rushton N

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO. 4. , Palacos R with ZrO. 2. and from CMW3 which contains BaSO. 4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 7 | Pages 962 - 970
1 Jul 2007
Albert C Patil S Frei H Masri B Duncan C Oxland T Fernlund G

This study explored the relationship between the initial stability of the femoral component and penetration of cement into the graft bed following impaction allografting.

Impaction allografting was carried out in human cadaveric femurs. In one group the cement was pressurised conventionally but in the other it was not pressurised. Migration and micromotion of the implant were measured under simulated walking loads. The specimens were then cross-sectioned and penetration of the cement measured.

Around the distal half of the implant we found approximately 70% and 40% of contact of the cement with the endosteum in the pressure and no-pressure groups, respectively. The distal migration/micromotion, and valgus/varus migration were significantly higher in the no-pressure group than in that subjected to pressure. These motion components correlated negatively with the mean area of cement and its contact with the endosteum.

The presence of cement at the endosteum appears to play an important role in the initial stability of the implant following impaction allografting.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 726 - 730
1 Jul 1998
Iwabu S Sasaki T Kameyama M Teruya T Horiuchi Y Yabe Y

We observed the healing process under rigid external fixation after Salter-Harris type-1 or type-2 physeal separation at the proximal tibia in immature rabbits.

Metaphyseal vessels grew across the gap with little delay; the site of separation then came to lie in the metaphysis and was bridged by endochondral ossification. Union was achieved within two days in all rabbits.

Progression of endochondral ossification repaired the separated physis, thus showing ‘primary healing of physeal separation’. This depends on accurate reduction and stable fixation to allow the survival of vessels across the gap.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 5 | Pages 758 - 764
1 Jul 2003
Granchi D Savarino L Ciapetti G Cenni E Rotini R Mieti M Baldini N Giunti A

We aimed to assess whether the immunological abnormalities which have been observed in patients with loose total hip replacements (THRs) are present in patients with a well-fixed prosthesis.

We examined blood samples from 39 healthy donors, 22 patients before THR and 41 with well-fixed THRs of different types (15 metal-on-metal, 13 metal-on-polyethylene, 13 ceramic-on-ceramic). Before THR, the patients showed a decrease in leukocytes and myeloid cells in comparison with healthy donors, and a prevalence of type-1 T lymphocytes, which was confirmed by the increase in ratio of interferon-γ to interleukin 4. Moreover, patients with metal-on-metal or metal-on-polyethylene implants showed a significant decrease in the number of T lymphocytes and a significant increase in the serum level of chromium and cobalt, although no significant correlation was observed with the immunological changes. In the ceramic-on-ceramic group, leukocytes and lymphocyte subsets were not significantly changed, but a significant increase in type-2 cytokines restored the ratio of interferon-γ to interleukin 4 to normal values.

We conclude that abnormalities of the cell-mediated immune response may be present in patients with a well-fixed THR, and that the immunological changes are more evident in those who have at least one metal component in the articular coupling.


Bone & Joint 360
Vol. 12, Issue 4 | Pages 44 - 46
1 Aug 2023
Burden EG Whitehouse MR Evans JT


Bone & Joint 360
Vol. 11, Issue 6 | Pages 49 - 50
1 Dec 2022
Evans JT Whitehouse MR


Bone & Joint 360
Vol. 12, Issue 5 | Pages 49 - 50
1 Oct 2023
Marson BA

This edition of Cochrane Corner looks at some of the work published by the Cochrane Collaboration, covering pharmacological interventions for the prevention of bleeding in people undergoing definitive fixation or joint replacement for hip, pelvic, and long bone fractures; interventions for reducing red blood cell transfusion in adults undergoing hip fracture surgery: an overview of systematic reviews; and pharmacological treatments for low back pain in adults: an overview of Cochrane Reviews


Bone & Joint 360
Vol. 13, Issue 4 | Pages 43 - 45
2 Aug 2024
Evans JT Evans JP Whitehouse MR


Bone & Joint 360
Vol. 13, Issue 2 | Pages 47 - 49
1 Apr 2024
Burden EG Krause T Evans JP Whitehouse MR Evans JT


Bone & Joint 360
Vol. 13, Issue 5 | Pages 51 - 52
1 Oct 2024
Marson BA

The Cochrane Collaboration has produced three new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner. These are relevant to a wide range of musculoskeletal specialists, and include reviews in lateral elbow pain, osteoarthritis of the big toe joint, and cervical spine injury in paediatric trauma patients.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 48 - 49
3 Jun 2024
Marson BA

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.


Bone & Joint 360
Vol. 12, Issue 6 | Pages 49 - 51
1 Dec 2023
Burden EG Whitehouse MR Evans JT


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint 360
Vol. 11, Issue 4 | Pages 44 - 46
1 Aug 2022
Evans JT Walton TJ Whitehouse MR


Bone & Joint 360
Vol. 11, Issue 1 | Pages 50 - 51
1 Feb 2022
Das A


Bone & Joint 360
Vol. 10, Issue 6 | Pages 48 - 50
1 Dec 2021
Evans JT French JMR Whitehouse MR


Bone & Joint 360
Vol. 10, Issue 4 | Pages 49 - 51
1 Aug 2021
Evans JT Welch M Whitehouse MR


Bone & Joint 360
Vol. 10, Issue 3 | Pages 38 - 39
1 Jun 2021
Das A


Bone & Joint 360
Vol. 10, Issue 2 | Pages 57 - 59
1 Apr 2021
Evans JT Whitehouse MR Evans JP


Bone & Joint Research
Vol. 8, Issue 2 | Pages 41 - 48
1 Feb 2019
Busse P Vater C Stiehler M Nowotny J Kasten P Bretschneider H Goodman SB Gelinsky M Zwingenberger S

Objectives. Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. Methods. Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. Results. Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. Conclusion. The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability. Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41–48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1


Bone & Joint Research
Vol. 8, Issue 2 | Pages 101 - 106
1 Feb 2019
Filardo G Petretta M Cavallo C Roseti L Durante S Albisinni U Grigolo B

Objectives. Meniscal injuries are often associated with an active lifestyle. The damage of meniscal tissue puts young patients at higher risk of undergoing meniscal surgery and, therefore, at higher risk of osteoarthritis. In this study, we undertook proof-of-concept research to develop a cellularized human meniscus by using 3D bioprinting technology. Methods. A 3D model of bioengineered medial meniscus tissue was created, based on MRI scans of a human volunteer. The Digital Imaging and Communications in Medicine (DICOM) data from these MRI scans were processed using dedicated software, in order to obtain an STL model of the structure. The chosen 3D Discovery printing tool was a microvalve-based inkjet printhead. Primary mesenchymal stem cells (MSCs) were isolated from bone marrow and embedded in a collagen-based bio-ink before printing. LIVE/DEAD assay was performed on realized cell-laden constructs carrying MSCs in order to evaluate cell distribution and viability. Results. This study involved the realization of a human cell-laden collagen meniscus using 3D bioprinting. The meniscus prototype showed the biological potential of this technology to provide an anatomically shaped, patient-specific construct with viable cells on a biocompatible material. Conclusion. This paper reports the preliminary findings of the production of a custom-made, cell-laden, collagen-based human meniscus. The prototype described could act as the starting point for future developments of this collagen-based, tissue-engineered structure, which could aid the optimization of implants designed to replace damaged menisci. Cite this article: G. Filardo, M. Petretta, C. Cavallo, L. Roseti, S. Durante, U. Albisinni, B. Grigolo. Patient-specific meniscus prototype based on 3D bioprinting of human cell-laden scaffold. Bone Joint Res 2019;8:101–106. DOI: 10.1302/2046-3758.82.BJR-2018-0134.R1


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. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1


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). Results. The OARSI score was significantly lower in mice treated with SRT1720 than in control mice at eight and 12 weeks associated with the decreased size of osteophytes at four and eight weeks. The delayed OA progression in the mice treated with SRT1720 was also associated with increased SIRT1-positive chondrocytes and decreased MMP-13-, ADAMTS-5-, cleaved caspase-3-, PARP p85-, and acetylated NF-κB p65-positive chondrocytes and decreased synovitis at four and eight weeks. SRT1720 treatment partially rescued the decreases in collagen type II alpha 1 (COL2A1) and aggrecan caused by IL-1β, while also reducing the induction of MMP-13 by IL-1β in vitro. Conclusion. The intraperitoneal injection of SRT1720 attenuated experimental OA progression in mice, indicating that SRT1720 could be a new therapeutic approach for OA. Cite this article: K. Nishida, T. Matsushita, K. Takayama, T. Tanaka, N. Miyaji, K. Ibaraki, D. Araki, N. Kanzaki, T. Matsumoto, R. Kuroda. Intraperitoneal injection of the SIRT1 activator SRT1720 attenuates the progression of experimental osteoarthritis in mice. Bone Joint Res 2018;7:252–262. DOI: 10.1302/2046-3758.73.BJR-2017-0227.R1


Bone & Joint Research
Vol. 7, Issue 1 | Pages 12 - 19
1 Jan 2018
Janz V Schoon J Morgenstern C Preininger B Reinke S Duda G Breitbach A Perka CF Geissler S

Objectives. The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). Methods. The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. Results. The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. Conclusion. The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species. Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12–19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2


Bone & Joint 360
Vol. 9, Issue 5 | Pages 49 - 50
1 Oct 2020
Das MA


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. Results. From the first post-operative day through to week 8 post-operatively, the median pain scores for the robotic arm-assisted group were 55.4% lower than those observed in the manual surgery group (p = 0.040). At three months post-operatively, the robotic arm-assisted group had better AKSS (robotic median 164, interquartile range (IQR) 131 to 178, manual median 143, IQR 132 to 166), although no difference was noted with the OKS. At one year post-operatively, the observed differences with the AKSS had narrowed from a median of 21 points to a median of seven points (p = 0.106) (robotic median 171, IQR 153 to 179; manual median 164, IQR 144 to 182). No difference was observed with the OKS, and almost half of each group reached the ceiling limit of the score (OKS > 43). A greater proportion of patients receiving robotic arm-assisted surgery improved their UCLA activity score. Binary logistic regression modelling for dichotomised outcome scores predicted the key factors associated with achieving excellent outcome on the AKSS: a pre-operative activity level > 5 on the UCLA activity score and use of robotic-arm surgery. For the same regression modelling, factors associated with a poor outcome were manual surgery and pre-operative depression. Conclusion. Robotic arm-assisted surgery results in improved early pain scores and early function scores in some patient-reported outcomes measures, but no difference was observed at one year post-operatively. Although improved results favoured the robotic arm-assisted group in active patients (i.e. UCLA ⩾ 5), these do not withstand adjustment for multiple comparisons. Cite this article: M. J. G. Blyth, I. Anthony, P. Rowe, M. S. Banger, A. MacLean, B. Jones. Robotic arm-assisted versus conventional unicompartmental knee arthroplasty: Exploratory secondary analysis of a randomised controlled trial. Bone Joint Res 2017;6:631–639. DOI: 10.1302/2046-3758.611.BJR-2017-0060.R1


Bone & Joint 360
Vol. 9, Issue 2 | Pages 46 - 48
1 Apr 2020
Evans JT Whitehouse MR


Bone & Joint Research
Vol. 9, Issue 4 | Pages 162 - 172
1 Apr 2020
Xie S Conlisk N Hamilton D Scott C Burnett R Pankaj P

Aims

Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA.

Methods

This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living.


Bone & Joint 360
Vol. 9, Issue 1 | Pages 10 - 14
1 Feb 2020
Ibrahim M Reito A Pidgaiska O


Bone & Joint Research
Vol. 4, Issue 3 | Pages 45 - 49
1 Mar 2015
Thompson MJ Ross J Domson G Foster W

Objectives. The clinical utility of routine cross sectional imaging of the abdomen and pelvis in the screening and surveillance of patients with primary soft-tissue sarcoma of the extremities for metastatic disease is controversial, based on its questionable yield paired with concerns regarding the risks of radiation exposure, cost, and morbidity resulting from false positive findings. Methods. Through retrospective review of 140 patients of all ages (mean 53 years; 2 to 88) diagnosed with soft-tissue sarcoma of the extremity with a mean follow-up of 33 months (0 to 291), we sought to determine the overall incidence of isolated abdominopelvic metastases, their temporal relationship to chest involvement, the rate of false positives, and to identify disparate rates of metastases based on sarcoma subtype. Results. A total of four patients (2.9%) exhibited isolated abdominopelvic metastatic disease during the surveillance period. In all cases of concomitant chest and abdominopelvic disease, chest involvement preceded abominopelvic involvement. There was a significant false positive rate requiring invasive workup. Conclusions. In the setting of a relative paucity of evidence concerning a rare disease process and in difference to recently published investigations, we add a clinical cohort not supportive of routine cross sectional imaging of the abdomen and pelvis. Cite this article: Bone Joint Res 2015;4:45–9


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 143 - 147
1 Jan 2004
Kaya M Wada T Nagoya S Kawaguchi S Isu K Yamashita T

Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom postoperative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 179 - 185
1 Jan 2010
Väänänen P Pajamäki I Paakkala A Nurmi JT Pajamäki J

We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score. All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement


Bone & Joint Research
Vol. 4, Issue 1 | Pages 6 - 10
1 Jan 2015
Goudie ST Deakin AH Deep K

Objectives. Acetabular component orientation in total hip arthroplasty (THA) influences results. Intra-operatively, the natural arthritic acetabulum is often used as a reference to position the acetabular component. Detailed information regarding its orientation is therefore essential. The aim of this study was to identify the acetabular inclination and anteversion in arthritic hips. Methods. Acetabular inclination and anteversion in 65 symptomatic arthritic hips requiring THA were measured using a computer navigation system. All patients were Caucasian with primary osteoarthritis (29 men, 36 women). The mean age was 68 years (SD 8). Mean inclination was 50.5° (SD 7.8) in men and 52.1° (SD 6.7) in women. Mean anteversion was 8.3° (SD 8.7) in men and 14.4° (SD 11.6) in women. . Results. The difference between men and women in terms of anteversion was significant (p = 0.022). In 75% of hips, the natural orientation was outside the safe zone described by Lewinnek et al (anteversion 15° ± 10°; inclination 40° ± 10°). Conclusion. When using the natural acetabular orientation to guide component placement, it is important to be aware of the differences between men and women, and that in up to 75% of hips natural orientation may be out of what many consider to be a safe zone. Cite this article: Bone Joint Res 2015;4:6–10


Bone & Joint 360
Vol. 8, Issue 4 | Pages 46 - 47
1 Aug 2019
Das A


Bone & Joint Research
Vol. 3, Issue 7 | Pages 236 - 240
1 Jul 2014
Robubi A Berger C Schmid M Huber KR Engel A Krugluger W

Objectives. Effects of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression of genes involved in the proliferation and differentiation of osteoblasts in culture were analysed. The best sequence of growth factor addition that induces expansion of cells before their differentiation was sought. Methods. Primary human osteoblasts in in vitro culture were treated with IGF1, BMP2 or FGF2 (10 ng/ml) for 24 hours (IGF1) or 48 hours (BMP2 and FGF2). Experiments were performed during the exponential growth phase with approximately 1e7 cells per 75 cm. 2. flask. mRNA was reverse transcribed directly and analysed using RT-PCR Taqman assays. Expression levels of key genes involved in cell growth and differentiation (CDH11, TNFRSF11B, RUNX2, POSTN, ALP, WNT5A, LEF1, HSPA5, FOS, p21) were monitored using RT-PCR with gene-specific Taqman probes. . Results. Autocrine expression of BMP2 is stimulated by FGF2 and BMP2 itself. BMP2 and FGF2 act as proliferative factors as indicated by reduced expression of ALP and POSTN, whereas IGF1 exhibits a more subtle picture: the Wingless und Int-1 (Wnt) signalling pathway and the Smad pathway, but not p38 mitogen-activated protein (MAP) kinase signalling, were shown to be activated by IGF1, leading to proliferation and differentiation of the cells. . Conclusions. For future use of autologous bone cells in the management of bony defects, new treatment options take advantage of growth factors and differentiation factors. Thus, our results might help to guide the timely application of these factors for the expansion and subsequent differentiation of osteoblastic cells in culture. Cite this article: Bone Joint Res 2014;3:236–40


Bone & Joint Research
Vol. 2, Issue 6 | Pages 102 - 111
1 Jun 2013
Patel RA Wilson RF Patel PA Palmer RM

Objectives. To review the systemic impact of smoking on bone healing as evidenced within the orthopaedic literature. Methods. A protocol was established and studies were sourced from five electronic databases. Screening, data abstraction and quality assessment was conducted by two review authors. Prospective and retrospective clinical studies were included. The primary outcome measures were based on clinical and/or radiological indicators of bone healing. This review specifically focused on non-spinal orthopaedic studies. Results. Nine tibia studies and eight other orthopaedic studies were considered for systematic review. Of these 17 studies, 13 concluded that smoking negatively influenced bone healing. Conclusions. Smoking has a negative effect on bone healing, in terms of delayed union, nonunion and more complications


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 5 | Pages 748 - 754
1 Jul 2000
Case CP Langkamer VG Lock RJ Perry MJ Palmer MR Kemp AJ

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1β, IL-6 and PGE. 2. in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 6 | Pages 973 - 978
1 Nov 1996
Malkani AL Voor MJ Fee KA Bates CS

We have tested the axial and torsional stability of femoral components after revision arthroplasty in a cadaver model, using impacted morsellised cancellous graft and cement. Each one of six matched pairs of fresh frozen human femora had either a primary or a revision prosthesis cemented in place. For the ‘revision’ experiments, all cancellous bone was removed from the proximal femur which was then over-reamed to create a smooth-walled cortical shell. An MTS servohydraulic test frame was used to apply axial and torsional loads to each specimen through the prosthetic femoral heads with the femur submerged in isotonic saline solution at 37°C. The mean subsidence was 0.27 ± 0.17 mm for the primary and 0.52 ± 0.30 mm for the revision groups. The difference was statistically significant (p < 0.025), but the mean subsidence was < 1 mm in both groups. The mean maximum torque before failure was 42.9 ± 26.9 N-m for the primary and 34.8± 20.7 N-m for the revision groups. This difference was not statistically significant (p > 0.015). Based on our results we suggest that revision of the femoral component using morsellised cancellous graft followed by cementing with a collarless prosthesis with a polished tapered stem restores the integrity of the proximal femur and provides immediate stability of the implant


Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

Methods

Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Nfat1-/- AC at the initiation stage of OA, and possessed at least four NFAT1 binding sites in the promoter of each gene, were selected and tested for NFAT1 transcriptional activities by chromatin immunoprecipitation (ChIP) and promoter luciferase reporter assays using chondrocytes isolated from the AC of three- to four-month-old wild-type mice or Nfat1-/- mice with early OA phenotype.


Bone & Joint Research
Vol. 8, Issue 3 | Pages 136 - 145
1 Mar 2019
Cerquiglini A Henckel J Hothi H Allen P Lewis J Eskelinen A Skinner J Hirschmann MT Hart AJ

Objectives

The Attune total knee arthroplasty (TKA) has been used in over 600 000 patients worldwide. Registry data show good clinical outcome; however, concerns over the cement-tibial interface have been reported. We used retrieval analysis to give further insight into this controversial topic.

Methods

We examined 12 titanium (Ti) PFC Sigma implants, eight cobalt-chromium (CoCr) PFC Sigma implants, eight cobalt-chromium PFC Sigma rotating platform (RP) implants, and 11 Attune implants. We used a peer-reviewed digital imaging method to quantify the amount of cement attached to the backside of each tibial tray. We then measured: 1) the size of tibial tray thickness, tray projections, peripheral lips, and undercuts; and 2) surface roughness (Ra) on the backside and keel of the trays. Statistical analyses were performed to investigate differences between the two designs.


Bone & Joint Research
Vol. 1, Issue 5 | Pages 71 - 77
1 May 2012
Keurentjes JC Van Tol FR Fiocco M Schoones JW Nelissen RG

Objectives. We aimed first to summarise minimal clinically important differences (MCIDs) after total hip (THR) or knee replacement (TKR) in health-related quality of life (HRQoL), measured using the Short-Form 36 (SF-36). Secondly, we aimed to improve the precision of MCID estimates by means of meta-analysis. Methods. We conducted a systematic review of English and non-English articles using MEDLINE, the Cochrane Controlled Trials Register (1960–2011), EMBASE (1991–2011), Web of Science, Academic Search Premier and Science Direct. Bibliographies of included studies were searched in order to find additional studies. Search terms included MCID or minimal clinically important change, THR or TKR and Short-Form 36. We included longitudinal studies that estimated MCID of SF-36 after THR or TKR. Results. Three studies met our inclusion criteria, describing a distinct study population: primary THR, primary TKR and revision THR. No synthesis of study results can be given. Conclusions. Although we found MCIDs in HRQoL after THR or TKR have limited precision and are not validated using external criteria, these are still the best known estimates of MCIDs in HRQoL after THR and TKR to date. We therefore advise these MCIDs to be used as absolute thresholds, but with caution


Bone & Joint Research
Vol. 8, Issue 1 | Pages 32 - 40
1 Jan 2019
Berger DR Centeno CJ Steinmetz NJ

Objectives

Platelet-rich plasma (PRP) is being used increasingly often in the clinical setting to treat tendon-related pathologies. Yet the optimal PRP preparations to promote tendon healing in different patient populations are poorly defined. Here, we sought to determine whether increasing the concentration of platelet-derived proteins within a derivative of PRP, platelet lysate (PL), enhances tenocyte proliferation and migration in vitro, and whether the mitogenic properties of PL change with donor age.

Methods

Concentrated PLs from both young (< 50 years) and aged (> 50 years) donors were prepared by exposing pooled PRP to a series of freeze-thaw cycles followed by dilution in plasma, and the levels of several platelet-derived proteins were measured using multiplex immunoassay technology. Human tenocytes were cultured with PLs to simulate a clinically relevant PRP treatment range, and cell growth and migration were assessed using DNA quantitation and gap closure assays, respectively.


Bone & Joint Research
Vol. 7, Issue 11 | Pages 587 - 594
1 Nov 2018
Zhang R Li G Zeng C Lin C Huang L Huang G Zhao C Feng S Fang H

Objectives

The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.

Methods

In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.


Bone & Joint 360
Vol. 7, Issue 5 | Pages 41 - 42
1 Oct 2018
Foy MA


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. 93-B, Issue 3 | Pages 421 - 426
1 Mar 2011
Maličev E Barlič A Kregar-Velikonja N Stražar K Drobnič M

The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1; collagen II, COL2; aggrecan, AGR; and versican, VER) were assessed. The cartilage differentiation indices (COL2/COL1, AGR/VER) were calculated. The control biopsies revealed a higher mean cell yield (1346 cells/mg vs 341 cells/mg), but similar cell proliferation, viability and morphology compared with the cells from the edge of the lesion. The cartilage differentiation indices were superior in control cells: COL2/COL1 (threefold in biopsies (non-significant)); sixfold in monolayer cultures (p = 0.012), and 7.5-fold in hydrogels (non-significant), AGR/VER (sevenfold in biopsies (p = 0.04), threefold (p = 0.003) in primary cultures and 3.5-fold in hydrogels (non-significant)). Our results suggest that the cultivation of chondrocytes solely from the edges of the lesion cannot be recommended for use in autologous chondrocyte implantation


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 120 - 127
1 Jan 2002
Musgrave DS Pruchnic R Bosch P Ziran BH Whalen J Huard J

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 609 - 617
1 May 2001
Wilke H Kemmerich V Claes LE Arand M

Fusion is the main goal in the surgical management of the injured and unstable spine. A wide variety of implants is available to enhance this. Our study was performed to evaluate the stabilising characteristics of several anterior, posterior and combined systems of fixation. Six thoracolumbar (T11 to L2) spines from 13-week-old calves were first tested intact. Then the vertebral body of T13 was removed and the defect replaced and supported by a wooden block to simulate bone grafting. Dorsal implants consisting of a Universal Spine System (USS) fracture system and an AO Fixateur interne (AOFI), and ventral implants comprising of a Kaneda Classic, a Kaneda SR, a prototype of the VentroFix single clamp/single rod construct (SC/SR) and the VentroFix single clamp/double rod construct (SC/DR) were first implanted individually to stabilise the removal of the vertebral body. Simulating the combined anteroposterior stabilisations, all ventral implants were combined with the AOFI. The range of motion (ROM) was measured under loads of up to 7.5 Nm. The load was applied in a custom-made spine tester in the three primary directions while measuring the intervertebral movements using a goniometric linkage system. The dorsal systems limited ROM in flexion below 0.9° and in extension between 3.3° and 3.6° (median values). The improved Kaneda System SR yielded a mean ROM of 1.8° in flexion and in extension. The median rotation found with the VentroFix (SC/DR) was 3.2° for flexion and 2.8° for extension. Reinforcement of the ventral constructs with a dorsal system reduced the ROM in flexion and extension in all cases to 0.4° and lower. In rotation, the median ROM of the anterior systems ranged from 2.7° to 5.1° and for the posterior systems from 3.9° to 5.7°, while the combinations provided a ROM of 1.2° to 1.9°. In lateral bending, the posterior implants restricted movement to 1.1°, whereas the anterior implants allowed up to 5.2°. The combined systems provided the highest stability at less than 0.6°. Our study revealed distinct differences between posterior and anterior approaches in all primary directions. Also, different stabilisation characteristics were found within the anterior and posterior groups. Combinations of these two approaches provided the highest stability in all directions


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 360
Vol. 7, Issue 3 | Pages 41 - 42
1 Jun 2018
Foy MA


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 973 - 979
1 Jul 2008
Savadkoohi DG Sadeghipour P Attarian H Sardari S Eslamifar A Shokrgozar MA

Curettage and packing with polymethylmethacrylate cement is a routine treatment for giant-cell tumour (GCT) of bone. We performed an in vitro evaluation of the cytotoxic effect of a combination of cement and methotrexate, doxorubicin and cisplatin on primary cell cultures of stromal GCT cells obtained from five patients. Cement cylinders containing four different concentrations of each drug were prepared, and the effect of the eluted drugs was examined at three different time intervals. We found that the cytotoxic effect of eluted drugs depended on their concentration and the time interval, with even the lowest dose of each drug demonstrating an acceptable rate of cytotoxicity. Even in low doses, cytotoxic drugs mixed with polymethylmethacrylate cement could therefore be considered as effective local adjuvant treatment for GCTs


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 114 - 121
1 Jan 2008
Pendegrass CJ Gordon D Middleton CA Sun SNM Blunn GW

Conventional amputation prostheses rely on the attachment of the socket to the stump, which may lead to soft-tissue complications. Intraosseous transcutaneous amputation prostheses (ITAPs) allow direct loading of the skeleton, but their success is limited by infection resulting from breaching of the skin at the interface with the implant. Keratinocytes provide the skin’s primary barrier function, while hemidesmosomes mediate their attachment to natural ITAP analogues. Keratinocytes must attach directly to the surface of the implant. We have assessed the proliferation, morphology and attachment of keratinocytes to four titaniumalloy surfaces in order to determine the optimal topography in vitro. We used immunolocalisation of adhesion complex components, scanning electron microscopy and transmission electron microscopy to assess cell parameters. We have shown that the proliferation, morphology and attachment of keratinocytes are affected by the surface topography of the biomaterials used to support their growth. Smoother surfaces improved adhesion. We postulate that a smooth topography at the point of epithelium-ITAP contact could increase attachment in vivo, producing an effective barrier of infection


Bone & Joint Research
Vol. 7, Issue 5 | Pages 362 - 372
1 May 2018
Ueda Y Inui A Mifune Y Sakata R Muto T Harada Y Takase F Kataoka T Kokubu T Kuroda R

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Methods

Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 244 - 251
1 Mar 2018
Tawonsawatruk T Sriwatananukulkit O Himakhun W Hemstapat W

Objectives

In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models.

Methods

OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score.


Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Methods

This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 274 - 281
1 Apr 2018
Collins KH Hart DA Seerattan RA Reimer RA Herzog W

Objectives

Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes.

Methods

A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 571 - 576
1 Apr 2005
Savarino L Granchi D Cenni E Baldini N Greco M Giunti A

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV). The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects. A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary


Bone & Joint Research
Vol. 7, Issue 1 | Pages 6 - 11
1 Jan 2018
Wong RMY Choy MHV Li MCM Leung K K-H. Chow S Cheung W Cheng JCY

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Materials and Methods

A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1257 - 1263
1 Sep 2006
Richter M Droste P Goesling T Zech S Krettek C

Different calcaneal plates with locked screws were compared in an experimental model of a calcaneal fracture. Four plate models were tested, three with uniaxially-locked screws (Synthes, Newdeal, Darco), and one with polyaxially-locked screws (90° ± 15°) (Rimbus). Synthetic calcanei were osteotomised to create a fracture model and then fixed with the plates and screws. Seven specimens for each plate model were subjected to cyclic loading (preload 20 N, 1000 cycles at 800 N, 0.75 mm/s), and load to failure (0.75 mm/s). During cyclic loading, the plate with polyaxially-locked screws (Rimbus) showed significantly lower displacement in the primary loading direction than the plates with uniaxially-locked screws (mean values of maximum displacement during cyclic loading: Rimbus, 3.13 mm (. sd. 0.68); Synthes, 3.46 mm (. sd. 1.25); Darco, 4.48 mm (. sd. 3.17); Newdeal, 5.02 mm (. sd. 3.79); one-way analysis of variance, p < 0.001). The increased stability of a plate with polyaxially-locked screws demonstrated during cyclic loading compared with plates with uniaxially-locked screws may be beneficial for clinical use


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 1019 - 1023
1 Jul 2005
Shimogaki K Yasunaga Y Ochi M

Acetabular dysplasia was produced in 24 immature white rabbits. A rotational acetabular osteotomy was then carried out and radiological and histological studies of the articular cartilage were made. In the hips which did not undergo osteotomy, radiographs at 26 weeks showed that residual subluxation remained and arthritic changes such as narrowing of the joint space or dislocation were still seen. However, in the operated group there was a remarkable increase in cover, but arthritic changes were not observed. After 24 weeks, the Mankin grading score in the operated group was significantly lower than that in the non-operated group. The latter hips showed an irregular surface of the cartilage, exfoliation and proliferation of synovial tissue. In those undergoing osteotomy, primary cloning of chondrocytes or hypercellularity was seen and at 24 weeks after operation and metaplasia of the cartilage in the fibrous tissue was observed in the boundary between the medial area of the acetabulum and the acetabular fossa


Bone & Joint Research
Vol. 6, Issue 11 | Pages 612 - 618
1 Nov 2017
Yin C Suen W Lin S Wu X Li G Pan X

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Methods

Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 958 - 965
1 Jul 2008
Leong JJH Leff DR Das A Aggarwal R Reilly P Atkinson HDE Emery RJ Darzi AW

The aim of this study was to validate the use of three models of fracture fixation in the assessment of technical skills. We recruited 21 subjects (six experts, seven intermediates, and eight novices) to perform three procedures: application of a dynamic compression plate on a cadaver porcine model, insertion of an unreamed tibial intramedullary nail, and application of a forearm external fixator, both on synthetic bone models. The primary outcome measures were the Objective Structural Assessment of technical skills global rating scale on video recordings of the procedures which were scored by two independent expert observers, and the hand movements of the surgeons which were analysed using the Imperial College Surgical Assessment Device. The video scores were significantly different for the three groups in all three procedures (p < 0.05), with excellent inter-rater reliability (α = 0.88). The novice and intermediate groups specifically were significantly different in their performance with dynamic compression plate and intramedullary nails (p < 0.05). Movement analysis distinguished between the three groups in the dynamic compression plate model, but a ceiling effect was demonstrated in the intramedullary nail and external fixator procedures, where intermediates and experts performed to comparable standards (p > 0.6). A total of 85% (18 of 21) of the subjects found the dynamic compression model and 57% (12 of 21) found all the models acceptable tools of assessment. This study has validated a low-cost, high-fidelity porcine dynamic compression plate model using video rating scores for skills assessment and movement analysis. It has also demonstrated that Synbone models for the application of and intramedullary nail and an external fixator are less sensitive and should be improved for further assessment of surgical skills in trauma. The availability of valid objective tools of assessment of surgical skills allows further studies into improving methods of training


Bone & Joint 360
Vol. 6, Issue 5 | Pages 42 - 44
1 Oct 2017
Ross A


Bone & Joint Research
Vol. 6, Issue 12 | Pages 640 - 648
1 Dec 2017
Xia B Li Y Zhou J Tian B Feng L

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Methods

Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 452 - 463
1 Jul 2017
Wang G Sui L Gai P Li G Qi X Jiang X

Objectives

Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.

Methods

We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.


Bone & Joint 360
Vol. 6, Issue 5 | Pages 39 - 40
1 Oct 2017
Das A


Bone & Joint Research
Vol. 6, Issue 10 | Pages 602 - 609
1 Oct 2017
Jin A Cobb J Hansen U Bhattacharya R Reinhard C Vo N Atwood R Li J Karunaratne A Wiles C Abel R

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Methods

Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 590 - 599
1 Oct 2017
Jefferson L Brealey S Handoll H Keding A Kottam L Sbizzera I Rangan A

Objectives

To explore whether orthopaedic surgeons have adopted the Proximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial results routinely into clinical practice.

Methods

A questionnaire was piloted with six orthopaedic surgeons using a ‘think aloud’ process. The final questionnaire contained 29 items and was distributed online to surgeon members of the British Orthopaedic Association and British Elbow and Shoulder Society. Descriptive statistics summarised the sample characteristics and fracture treatment of respondents overall, and grouped them by whether they changed practice based on PROFHER trial findings. Free-text responses were analysed qualitatively for emerging themes using Framework Analysis principles.


Bone & Joint Research
Vol. 6, Issue 8 | Pages 464 - 471
1 Aug 2017
Li QS Meng FY Zhao YH Jin CL Tian J Yi XJ

Objectives

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing.

Methods

Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p.


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 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.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 7 | Pages 1075 - 1081
1 Sep 2001
Doherty AT Howell RT Ellis LA Bisbinas I Learmonth ID Newson R Case CP

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 2 | Pages 292 - 298
1 Mar 2003
Pasque C Noyes FR Gibbons M Levy M Grood E

Techniques for the selective cutting of ligaments in cadaver knees defined the static contributions of the posterolateral structures to external rotation, varus rotation and posterior tibial translation from 0° to 120° of flexion under defined loading conditions. Sectioning of the popliteofibular ligament (PFL) (group 1) produced no significant changes in the limits of the knee movement studied. Sectioning of the PFL and the popliteus tendon (femoral attachment, group 2) produced an increase of only 5° to 6° in external rotation from flexion of 30° to 120° (p < 0.001). Even when other ligaments were sectioned first (group 3), the maximum effect of the PFL was negligible. Our findings show that the popliteus muscle-tendon-ligament complex, lateral collateral ligament, and posterolateral capsular structures function as a unit. No individual structure alone is the primary restraint for the movements studied. Operative reconstruction should address all of the posterolateral structures, since restoration of only a portion may result in residual instability


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 328 - 332
1 Mar 1999
Yamamoto T DiCarlo EF Bullough PG

In about 50% of cases, osteonecrosis of the femoral head is known to occupy more than one site. There is controversy as to whether a single focus may increase in size. We have reviewed 606 consecutive femoral heads which had been surgically removed for osteonecrosis. Extension of osteonecrosis was observed in only two (0.3%) and was confirmed histopathologically by the enlargement of the necrotic segment beyond the repair zone formed for the primary necrosis into the adjacent, previously uninvolved bone. In both cases, the necrotic regions were wedge-shaped and occupied over 80% of the femoral head. It appears that an increase in size is extremely rare and that osteonecrosis is due to a single event. Our findings may be of value in assessing the use of joint-salvage procedures for osteonecrosis of the femoral head


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 4 | Pages 641 - 646
1 Jul 1996
Aspenberg P Herbertsson P

Using a rat model, we created a bone-to-titanium interface and applied phagocytosable high-density polyethylene pArticles between the bone and implant, either initially or when the interface had matured. No fibrous membrane developed and no bone resorption was found. If sliding movements were initiated at the interface after two weeks, there was formation of a fibrous membrane. The additional application of pArticles did not change the thickness of the membrane, and there were only minor qualitative changes. Creation of a membrane by movement followed by cessation of movement and the application of pArticles caused the membrane to persist, whereas in a pArticle-free control group bone-to-metal contact was re-established. Our findings suggest that mechanical stimuli are of primary importance for prosthetic loosening, and that pArticles may modulate the later stages of the loosening process


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 139 - 143
1 Jan 2001
Fini M Giavaresi G Torricelli P Krajewski A Ravaglioli A Belmonte MM Biagini G Giardino R

We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro. In normal bone the rate of osseointegration was similar for all materials tested (p > 0.5) while in osteopenic bone AP40 did not osseointegrate (p > 0.0005). In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40. Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro


Bone & Joint Research
Vol. 6, Issue 4 | Pages 231 - 244
1 Apr 2017
Zhang J Yuan T Zheng N Zhou Y Hogan MV Wang JH

Objectives

After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP).

Methods

Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing.


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 3 | Pages 440 - 447
1 Apr 2003
Røkkum M Reigstad A Johansson CB Albrektsson T

Ten acetabular cups coated with hydroxyapatite (HA) had originally been inserted in five primary and five revision total hip replacements. The thickness of the HA was 155 ± 35 μm. The cups, which were well-fixed, were retrieved, with their adherent tissue, at reoperation after 0.3 to 5.8 years because of infection (five hips), wear of polyethylene (three hips), and instability (two hips). Undecalcified sections showed a direct contact between bone and osteoid-like tissue which had formed directly onto the HA coating. The area within the threads and their mirror images, as well as the implant-tissue interfaces consisted of similar amounts of bone and soft tissue. Degradation of HA was seen in all hips. The mean thickness of the remaining HA coating was 97 μm (95% CI 94 to 101). The metal interface comprised 66% HA. The HA-tissue interface contained more bone than soft tissue (p = 0.001), whereas the metal-tissue interface included more soft tissue than bone (p = 0.019). Soft tissue at the implant interface and poor replacement of HA by bone may interfere with long-term fixation


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 604 - 608
1 May 2001
Fink B Berger I Siegmüller C Fassbender H Meyer-Scholten C Tillmann K Rüther W

We evaluated histologically samples of synovial tissue from the knees of 50 patients with rheumatoid arthritis (RA). The samples were taken during revision for aseptic loosening. The findings were compared with those in 64 knees with osteoarthritis (OA) and aseptic loosening and in 18 knees with RA without loosening. The last group had been revised because of failure of the inlay or the coupling system of a constrained prosthesis. All the patients had had a total ventral synovectomy before implantation of the primary prosthesis. In all three groups a foreign-body reaction and lymphocellular infiltration were seen in more than 80% of the tissue samples. Deposits of fibrin were observed in about one-third to one-half of the knees in all groups. Typical signs of the reactivation of RA such as rheumatoid necrosis and/or proliferation of synovial stromal cells were found in 26% of knees with RA and loosening, but not in those with OA and loosening and in those with RA without loosening. Our findings show that reactivation of rheumatoid synovitis occurs after total knee replacement and may be a cofactor in aseptic loosening in patients with RA


Bone & Joint Research
Vol. 6, Issue 6 | Pages 366 - 375
1 Jun 2017
Neves N Linhares D Costa G Ribeiro CC Barbosa MA

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.

Methods

A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 277 - 283
1 May 2017
Yoshikawa M Nakasa T Ishikawa M Adachi N Ochi M

Objectives

Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine.

Methods

Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs).


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 5 | Pages 760 - 767
1 Jul 2000
Watanabe H Shinozaki T Yanagawa T Aoki J Tokunaga M Inoue T Endo K Mohara S Sano K Takagishi K

We performed positron emission tomography (PET) with . 18. fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (≥ 1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 124 - 129
1 Jan 2001
Lofthouse RA Davis JR Frondoza CG Jinnah RH Hungerford DS Hare JM

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype. There is little information on the precise function of caveolae, but it has been proposed that they play an important role in signal transduction. As the principal bone-producing cell, the osteoblast has been widely studied in an effort to understand the signalling pathways by which it responds to extracellular stimuli. Our aim in this study was to identify caveolae and their structural protein caveolin in normal human osteoblasts, and to determine which subtypes of caveolin were present. Confocal microscopy showed staining which was associated with the plasma membrane. Transmission electron microscopy revealed the presence of membrane invaginations of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated protein from these osteoblasts, and performed Western blotting using anti-caveolin primary antibodies. This revealed the presence of caveolin-1 and -2, while caveolin-3 was absent. The identification of these structures and their associated protein may provide a significant contribution to our further understanding of signal transduction pathways in osteoblasts


Bone & Joint Research
Vol. 6, Issue 5 | Pages 296 - 306
1 May 2017
Samara E Moriarty TF Decosterd LA Richards RG Gautier E Wahl P

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Methods

In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 14 - 21
1 Jan 2017
Osagie-Clouard L Sanghani A Coathup M Briggs T Bostrom M Blunn G

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 6 | Pages 1024 - 1030
1 Nov 1997
Pazzaglia UE Andrini L Di Nucci A

We have used an experimental model employing the bent tail of rats to investigate the effects of mechanical forces on bones and joints. Mechanical strain could be applied to the bones and joints of the tail without direct surgical exposure or the application of pins and wires. The intervertebral disc showed stretched annular lamellae on the convex side, while the annulus fibrosus on the concave side was pinched between the inner corners of the vertebral epiphysis. In young rats with an active growth plate, a transverse fissure appeared at the level of the hypertrophic cell layer or the primary metaphyseal trabecular zone. Metaphyseal and epiphyseal trabeculae on the compressed side were thicker and more dense than those of the distracted part of the vertebra. In growing animals, morphometric analysis of hemiepiphyseal and hemimetaphyseal areas, and the corresponding trabecular bone density, showed significant differences between the compressed and distracted sides. No differences were observed in adult rats. We found no significant differences in osteoclast number between compressed and distracted sides in either age group. Our results provide quantitative evidence of the working of ‘Wolff’s law’. The differences in trabecular density are examples of remodelling by osteoclasts and osteoblasts; our finding of no significant difference in osteoclast numbers between the hemiepiphyses in the experimental and control groups suggests that the response of living bone to altered strain is mediated by osteoblasts


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 128 - 136
1 Jan 2002
Böhler M Kanz F Schwarz B Steffan I Walter A Plenk H Knahr K

We revised seven alumina-blasted cementless hip prostheses (Ti-alloy stems, cp Ti threaded sockets) with low- or high-carbon Co-alloy bearings at a mean of 20.1 months after implantation because of pain and loosening. Histological examination of the retrieved periprosthetic tissues from two cases in which the implant was stable and three in which the socket was loose showed macrophages with basophilic granules containing metal and alumina wear particles and lymph-cell infiltrates. In one of the two cases of stem loosening the thickened neocapsule also contained definite lymphatic follicles and gross lymphocyte/plasma-cell infiltrates. Spectrometric determination of the concentration of elements in periprosthetic tissues from six cases was compared with that of joint capsules from five control patients undergoing primary hip surgery. In the revisions the mean concentration of implant-relevant elements was 693.85 μg/g dry tissue. In addition to Cr (15.2%), Co (4.3%), and Ti (10.3%), Al was predominant (68.1%) and all concentrations were significantly higher (p < 0.001) than those in the control tissues. The annual rates of linear wear were calculated for six implants. The mean value was 11.1 μm (heads 6.25 μm, inserts 4.82 μm). SEM/EDXA showed numerous fine scratches and deep furrows containing alumina particles in loosened sockets, and stems showed contamination with adhering or impacted alumina particles of between 2 and 50 μm in size


Bone & Joint Research
Vol. 6, Issue 2 | Pages 90 - 97
1 Feb 2017
Rajfer RA Kilic A Neviaser AS Schulte LM Hlaing SM Landeros J Ferrini MG Ebramzadeh E Park S

Objectives

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days.

Materials and Methods

Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives

Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts.

Methods

Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 52 - 56
1 Jan 2017
Hothi HS Kendoff D Lausmann C Henckel J Gehrke T Skinner J Hart A

Objectives

Mechanical wear and corrosion at the head-stem junction of total hip arthroplasties (THAs) (trunnionosis) have been implicated in their early revision, most commonly in metal-on-metal (MOM) hips. We can isolate the role of the head-stem junction as the predominant source of metal release by investigating non-MOM hips; this can help to identify clinically significant volumes of material loss and corrosion from these surfaces.

Methods

In this study we examined a series of 94 retrieved metal-on-polyethylene (MOP) hips for evidence of corrosion and material loss at the taper junction using a well published visual grading method and an established roundness-measuring machine protocol. Hips were retrieved from 74 male and 20 female patients with a median age of 57 years (30 to 76) and a median time to revision of 215 months (2 to 324). The reasons for revision were loosening of both the acetabular component and the stem (n = 29), loosening of the acetabular component (n = 58) and infection (n = 7). No adverse tissue reactions were reported by the revision surgeons.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 123 - 131
1 Mar 2017
Sasaki T Akagi R Akatsu Y Fukawa T Hoshi H Yamamoto Y Enomoto T Sato Y Nakagawa R Takahashi K Yamaguchi S Sasho T

Objectives

The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model.

Methods

MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium.

A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 179 - 185
1 Mar 2017
Wu JH Thoreson AR Gingery A An KN Moran SL Amadio PC Zhao C

Objectives

The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an ex vivo canine model.

Methods

Specifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young’s modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey’s post hoc multiple-comparison test.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 610 - 618
1 Dec 2016
Abubakar AA Noordin MM Azmi TI Kaka U Loqman MY

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.

Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.