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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. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1


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 Research
Vol. 5, Issue 6 | Pages 253 - 262
1 Jun 2016
Liu H Li W Liu YS Zhou YS

Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262


Bone & Joint Research
Vol. 6, Issue 9 | Pages 542 - 549
1 Sep 2017
Arnold M Zhao S Ma S Giuliani F Hansen U Cobb JP Abel RL Boughton O

Objectives. Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness. Methods. A systematic review of all English language articles using a keyword search was undertaken using Medline, Embase, PubMed, Scopus and Cochrane databases. Studies that only used nanoindentation, cancellous bone or animal tissue were excluded. Results. A total of 1094 abstracts were retrieved and 32 papers were included in the analysis, 20 of which used reference point indentation, and 12 of which used traditional depth-sensing indentation. There are several factors that must be considered when using microindentation, such as tip size, depth and method of analysis. Only two studies validated microindentation against traditional mechanical testing techniques. Both studies used reference point indentation (RPI), with one showing that RPI parameters correlate well with mechanical testing, but the other suggested that they do not. Conclusion. Microindentation has been used in various studies to assess bone stiffness, but only two studies with conflicting results compared microindentation with traditional mechanical testing techniques. Further research, including more studies comparing microindentation with other mechanical testing methods, is needed before microindentation can be used reliably to calculate cortical bone stiffness. Cite this article: M. Arnold, S. Zhao, S. Ma, F. Giuliani, U. Hansen, J. P. Cobb, R. L. Abel, O. Boughton. Microindentation – a tool for measuring cortical bone stiffness? A systematic review. Bone Joint Res 2017;6:542–549. DOI: 10.1302/2046-3758.69.BJR-2016-0317.R2


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. 4, Issue 10 | Pages 170 - 175
1 Oct 2015
Sandberg OH Aspenberg P

Objectives. Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. Methods. We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. Results. As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. Conclusions. It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170–175


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

Objectives

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

Materials and Methods

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


Bone & Joint Research
Vol. 6, Issue 8 | Pages 522 - 529
1 Aug 2017
Ali AM Newman SDS Hooper PA Davies CM Cobb JP

Objectives

Unicompartmental knee arthroplasty (UKA) is a demanding procedure, with tibial component subsidence or pain from high tibial strain being potential causes of revision. The optimal position in terms of load transfer has not been documented for lateral UKA. Our aim was to determine the effect of tibial component position on proximal tibial strain.

Methods

A total of 16 composite tibias were implanted with an Oxford Domed Lateral Partial Knee implant using cutting guides to define tibial slope and resection depth. Four implant positions were assessed: standard (5° posterior slope); 10° posterior slope; 5° reverse tibial slope; and 4 mm increased tibial resection. Using an electrodynamic axial-torsional materials testing machine (Instron 5565), a compressive load of 1.5 kN was applied at 60 N/s on a meniscal bearing via a matching femoral component. Tibial strain beneath the implant was measured using a calibrated Digital Image Correlation system.


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.


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.


Objectives

Preservation of both anterior and posterior cruciate ligaments in total knee arthroplasty (TKA) can lead to near-normal post-operative joint mechanics and improved knee function. We hypothesised that a patient-specific bicruciate-retaining prosthesis preserves near-normal kinematics better than standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining prostheses in TKA.

Methods

We developed the validated models to evaluate the post-operative kinematics in patient-specific bicruciate-retaining, standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under gait and deep knee bend loading conditions using numerical simulation.


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

Objectives

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

Materials and Methods

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


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

Objectives

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

Materials and Methods

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


Bone & Joint Research
Vol. 3, Issue 7 | Pages 230 - 235
1 Jul 2014
van der Jagt OP van der Linden JC Waarsing JH Verhaar JAN Weinans H

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Methods

EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 276 - 279
1 Jun 2016
Zhu H Gao Y Wang Y Zhang C

Objectives

Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH).

Methods

We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis.


Bone & Joint Research
Vol. 1, Issue 1 | Pages 1 - 7
1 Jan 2012
Rosenberg N Rosenberg O

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.

Methods

Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining.


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.


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

Objectives

This study aims to assess the correlation of CT-based structural rigidity analysis with mechanically determined axial rigidity in normal and metabolically diseased rat bone.

Methods

A total of 30 rats were divided equally into normal, ovariectomized, and partially nephrectomized groups. Cortical and trabecular bone segments from each animal underwent micro-CT to assess their average and minimum axial rigidities using structural rigidity analysis. Following imaging, all specimens were subjected to uniaxial compression and assessment of mechanically-derived axial rigidity.