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Bone & Joint Research
Vol. 10, Issue 9 | Pages 611 - 618
27 Sep 2021
Ali E Birch M Hopper N Rushton N McCaskie AW Brooks RA

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Methods

Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1158 - 1164
1 Sep 2013
Ahmad Z Siddiqui N Malik SS Abdus-Samee M Tytherleigh-Strong G Rushton N

Lateral epicondylitis, or ’tennis elbow’, is a common condition that usually affects patients between 35 and 55 years of age. It is generally self-limiting, but in some patients it may continue to cause persistent symptoms, which can be refractory to treatment. This review discusses the mechanism of disease, symptoms and signs, investigations, current management protocols and potential new treatments.

Cite this article: Bone Joint J 2013;95-B:1158–64.


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

Objectives

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

Methods

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


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 565 - 576
1 May 2009
Getgood A Brooks R Fortier L Rushton N

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.


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

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

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

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


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1110 - 1115
1 Aug 2006
Ong KL Kurtz SM Manley MT Rushton N Mohammed NA Field RE

The effects of the method of fixation and interface conditions on the biomechanics of the femoral component of the Birmingham hip resurfacing arthroplasty were examined using a highly detailed three-dimensional computer model of the hip. Stresses and strains in the proximal femur were compared for the natural femur and for the femur resurfaced with the Birmingham hip resurfacing. A comparison of cemented versus uncemented fixation showed no advantage of either with regard to bone loading. When the Birmingham hip resurfacing femoral component was fixed to bone, proximal femoral stresses and strains were non-physiological. Bone resorption was predicted in the inferomedial and superolateral bone within the Birmingham hip resurfacing shell. Resorption was limited to the superolateral region when the stem was not fixed. The increased bone strain observed adjacent to the distal stem should stimulate an increase in bone density at that location. The remodelling of bone seen during revision of failed Birmingham hip resurfacing implants appears to be consistent with the predictions of our finite element analysis.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1344 - 1351
1 Oct 2005
Field RE Rushton N

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone.

The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption.

The mean Barthel index and the Charnley-modified Merle d’Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1093 - 1099
1 Nov 2004
Lynn AK Brooks RA Bonfield W Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 6 | Pages 912 - 917
1 Aug 2004
Beeton CA Chatfield D Brooks RA Rushton N

There is evidence that fractures heal more rapidly in patients with head injury. We measured the circulating level of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) in serum from patients who had sustained a head injury with and without fracture and compared these with levels found in control subjects.

Within 12 hours of injury the serum level of IL-6 was significantly higher in patients with head injury and fracture compared with the control group. Levels of IL-6 were also significantly higher in patients with head injury and fracture compared with fracture only. While there was no significant difference in circulating levels of sIL-6R in the initial samples they were increased one week after surgery in patients with head injury and fracture and with head injury only. In addition, reduced levels of sgp130 in patients with head injury with and without fracture indicated a possible reduction of the inhibitory effect of this protein on the activity of IL-6.

Our study suggests that IL-6 may be involved in altered healing of a fracture after head injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 126 - 134
1 Jan 2004
Clarke SA Brooks RA Lee PT Rushton N

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty.

We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed.

TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 1 | Pages 152 - 152
1 Jan 2004
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 2 | Pages 310 - 310
1 Mar 2003
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 2 | Pages 311 - 311
1 Mar 2003
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 4 | Pages 622 - 622
1 May 2002
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 4 | Pages 622 - 622
1 May 2002
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 3 | Pages 434 - 439
1 Apr 2002
Beeton CA Brooks RA Chatfield D Human M Rushton N

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures.

The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01).

Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 2 | Pages 295 - 299
1 Mar 2002
Brooks RA Wimhurst JA Rushton N

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results.

Four different formulations of cement were found to be free from endotoxin using standard, gelclot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen.

Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 5 | Pages 775 - 777
1 Jul 2001
Rushton N


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 588 - 592
1 May 2001
Wimhurst JA Brooks RA Rushton N

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO2) and with barium sulphate (BaSO4). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 109 particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis.

All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO4-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO4 is used as the radiopaque agent.


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 BaSO4, Palacos R with ZrO2 and from CMW3 which contains BaSO4. 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.