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. 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.Objectives
Methods
We conducted a case-control study to examine
the merit of silver-coated tumour prostheses. We reviewed 85 patients
with Agluna-treated (silver-coated) tumour implants treated between
2006 and 2011 and matched them with 85 control patients treated
between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4
to 90.4) were included in the study. There were 50 primary reconstructions
(29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions
for infection (24.1%). The overall post-operative infection rate of the silver-coated
group was 11.8% compared with 22.4% for the control group (p = 0.033,
chi-square test). A total of seven of the ten infected prostheses
in the silver-coated group were treated successfully with debridement,
antibiotics, and implant retention compared with only six of the
19 patients (31.6%) in the control group (p = 0.048, chi-square
test). Three patients in the silver-coated group (3.5%) and 13 controls
(15.3%) had chronic periprosthetic infection (p = 0.009, chi-square
test). The overall success rates in controlling infection by two-stage
revision in the silver-coated group was 85% (17/20) compared with
57.1% (12/21) in the control group (p = 0.05, chi-square test).
The Agluna-treated endoprostheses were associated with a lower rate
of early periprosthetic infection. These silver-treated implants
were particularly useful in two-stage revisions for infection and
in those patients with incidental positive cultures at the time
of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant
appeared to be more successful with silver-coated implants. Cite this article:
Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles. Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure.
Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft.Objectives
Methods
In order to ensure safety of the cell-based therapy for bone
regeneration, we examined BM cells obtained from a total of 13 Sprague-Dawley (SD) green
fluorescent protein transgenic (GFP-Tg) rats were culture-expanded
in an osteogenic differentiation medium for three weeks. Osteoblast-like
cells were then locally transplanted with collagen scaffolds to
the rat model of segmental bone defect. Donor cells were also intravenously infused
to the normal Sprague-Dawley (SD) rats for systemic biodistribution.
The flow cytometric and histological analyses were performed for
cellular tracking after transplantation.Objectives
Methods
Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
Total knee replacement (TKR) is an effective
method of treating end-stage arthritis of the knee. It is not, however,
a procedure without risk due to a number of factors, one of which
is diabetes mellitus. The purpose of this study was to estimate
the general prevalence of diabetes in patients about to undergo
primary TKR and to determine whether diabetes mellitus adversely
affects the outcome. We conducted a systematic review and meta-analysis
according to the Meta-analysis Of Observational Studies in Epidemiology
(MOOSE) guidelines. The Odds Ratio (OR) and mean difference (MD)
were used to represent the estimate of risk of a specific outcome.
Our results showed the prevalence of diabetes mellitus among patients
undergoing TKR was 12.2%. Patients with diabetes mellitus had an increased
risk of deep infection (OR = 1.61, 95% confidence interval (CI),
1.38 to 1.88), deep vein thrombosis (in Asia, OR = 2.57, 95% CI,
1.58 to 4.20), periprosthetic fracture (OR = 1.89, 95% CI, 1.04
to 3.45), aseptic loosening (OR = 9.36, 95% CI, 4.63 to 18.90),
and a poorer Knee Society function subscore (MD = -5.86, 95% CI,
-10.27 to -1.46). Surgeons should advise patients specifically about
these increased risks when obtaining informed consent and be meticulous about
their peri-operative care. Cite this article:
Periosteum is important for bone homoeostasis
through the release of bone morphogenetic proteins (BMPs) and their
effect on osteoprogenitor cells. Smoking has an adverse effect on
fracture healing and bone regeneration. The aim of this study was
to evaluate the effect of smoking on the expression of the BMPs
of human periosteum. Real-time polymerase chain reaction was performed
for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from
45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured
bones (21 smokers, 39 non-smokers). A hierarchical model of BMP
gene expression (BMP-2 >
BMP-6 >
BMP-4 >
BMP-7) was demonstrated
in all samples. When smokers and non-smokers were compared, a remarkable
reduction in the gene expression of BMP-2, -4 and -6 was noticed
in smokers. The comparison of fracture and non-fracture groups demonstrated
a higher gene expression of BMP-2, -4 and -7 in the non-fracture
samples. Within the subgroups (fracture and non-fracture), BMP gene
expression in smokers was either lower but without statistical significance
in the majority of BMPs, or similar to that in non-smokers with
regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In
smokers, BMP gene expression of human periosteum was reduced, demonstrating
the effect of smoking at the molecular level by reduction of mRNA
transcription of periosteal BMPs. Among the BMPs studied, BMP-2
gene expression was significantly
There are many guidelines that help direct the management of
patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken
a study to compare the management of patients with MOM hip arthroplasties in
different countries. Six international tertiary referral orthopaedic centres were
invited to participate by organising a multi-disciplinary team (MDT)
meeting, consisting of two or more revision hip arthroplasty surgeons
and a musculoskeletal radiologist. A full clinical dataset including
history, blood tests and imaging for ten patients was sent to each
unit, for discussion and treatment planning. Differences in the
interpretation of findings, management decisions and rationale for
decisions were compared using quantitative and qualitative methods.Aims
Methods
This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay.Objectives
Methods
Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells. Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing. After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times. Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.
Recently, the use of metal-on-metal articulations
in total hip arthroplasty (THA) has led to an increase in adverse
events owing to local soft-tissue reactions from metal ions and
wear debris. While the majority of these implants perform well,
it has been increasingly recognised that a small proportion of patients
may develop complications secondary to systemic cobalt toxicity
when these implants fail. However, distinguishing true toxicity
from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt
alloys in THA and to highlight the following related topics of interest:
mechanisms of cobalt ion release and their measurement, definitions
of pathological cobalt ion levels, and the pathophysiology, risk factors
and treatment of cobalt toxicity. Historically, these metal-on-metal
arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative
stresses placed on the prosthetic joint. It exerts its pathological
effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt
toxicity in patients with metal-on-metal hip arthroplasties. Take home message: Patients with new or evolving hip symptoms
with a prior history of THA warrant orthopaedic surgical evaluation.
Increased awareness of the range of systemic symptoms associated
with cobalt toxicity, coupled with prompt orthopaedic intervention, may
forestall the development of further complications. Cite this article:
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. 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.Objectives
Methods
The most frequent cause of failure after total
hip replacement in all reported arthroplasty registries is peri-prosthetic
osteolysis. Osteolysis is an active biological process initiated
in response to wear debris. The eventual response to this process
is the activation of macrophages and loss of bone. Activation of macrophages initiates a complex biological cascade
resulting in the final common pathway of an increase in osteolytic
activity. The biological initiators, mechanisms for and regulation
of this process are beginning to be understood. This article explores current
concepts in the causes of, and underlying biological mechanism resulting
in peri-prosthetic osteolysis, reviewing the current basic science
and clinical literature surrounding the topic.
Recent studies have shown that modulating inflammation-related
lipid signalling after a bone fracture can accelerate healing in
animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity
during fracture healing increases cyclooxygenase-2 (COX-2) expression
in the fracture callus, accelerates chondrogenesis and decreases
healing time. In this study, we test the hypothesis that 5-LO inhibition
will increase direct osteogenesis. Bilateral, unicortical femoral defects were used in rats to measure
the effects of local 5-LO inhibition on direct osteogenesis. The
defect sites were filled with a polycaprolactone (PCL) scaffold
containing 5-LO inhibitor (A-79175) at three dose levels, scaffold
with drug carrier, or scaffold only. Drug release was assessed Objectives
Methods
The June 2012 Trauma Roundup360 looks at: nerve injuries of warfare; the medical complications of earthquakes; the measuring of tissue pressures in compartment syndrome; the risk of plunging through the bone when drilling; bony nonunion and negative pressure therapy; surgery for the posteriorly dislocated hip; whether to use the sliding screw or intramedullary nail for the trochanteric fracture; antegrade interlocking nailing for the distal femoral fracture; and gunshot wounds to the pancreas.
The number of arthroplasties being undertaken
is expected to grow year on year, and periprosthetic joint infections will
be an increasing socioeconomic burden. The challenge to prevent
and eradicate these infections has resulted in the emergence of
several new strategies, which are discussed in this review. Cite this article:
An experimental rabbit model was used to test the null hypothesis,
that there is no difference in new bone formation around uncoated
titanium discs compared with coated titanium discs when implanted
into the muscles of rabbits. A total of three titanium discs with different surface and coating
(1, porous coating; 2, porous coating + Bonemaster (Biomet); and
3, porous coating + plasma-sprayed hydroxyapatite) were implanted
in 12 female rabbits. Six animals were killed after six weeks and
the remaining six were killed after 12 weeks. The implants with
surrounding tissues were embedded in methyl methacrylate and grinded
sections were stained with Masson-Goldners trichrome and examined
by light microscopy of coded sections.Objectives
Methods
In this paper we propose a new classification
of neurogenic peri-articular heterotopic ossification (HO) of the
hip based on three-dimensional (3D) CT, with the aim of improving
pre-operative planning for its excision. A total of 55 patients (73 hips) with clinically significant
HO after either traumatic brain or spinal cord injury were assessed
by 3D-CT scanning, and the results compared with the intra-operative
findings. At operation, the gross pathological anatomy of the HO as identified
by 3D-CT imaging was confirmed as affecting the peri-articular hip
muscles to a greater or lesser extent. We identified seven patterns
of involvement: four basic (anterior, medial, posterior and lateral)
and three mixed (anteromedial, posterolateral and circumferential).
Excellent intra- and inter-observer agreement, with kappa values
>
0.8, confirmed the reproducibility of the classification system. We describe the different surgical approaches used to excise
the HO which were guided by the 3D-CT findings. Resection was always
successful. 3D-CT imaging, complemented in some cases by angiography, allows
the surgeon to define the 3D anatomy of the HO accurately and to
plan its surgical excision with precision. Cite this article:
The ability of mesenchymal stem cells (MSCs)
to differentiate Despite their increasing application in clinical trials, the
origin and role of MSCs in the development, repair and regeneration
of organs have remained unclear. Until recently, MSCs could only
be isolated in a process that requires culture in a laboratory;
these cells were being used for tissue engineering without understanding
their native location and function. MSCs isolated in this indirect
way have been used in clinical trials and remain the reference standard
cellular substrate for musculoskeletal engineering. The therapeutic
use of autologous MSCs is currently limited by the need for In this annotation we provide an update on the recent developments
in the understanding of the identity of MSCs within tissues and
outline how this may affect their use in orthopaedic surgery in
the future. Cite this article: