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. 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.Objectives
Materials and Methods
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. 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.Objectives
Methods
This is the first prospective study to report the pre- and post-operative
patient reported outcomes and satisfaction scores following excision
of interdigital Morton’s neuroma. Between May 2006 and April 2013, we prospectively studied 99
consecutive patients (111 feet) who were to undergo excision of
a Morton’s neuroma. There were 78 women and 21 men with a mean age
at the time of surgery of 56 years (22 to 78). Patients completed
the Manchester-Oxford Foot Questionnaire (MOXFQ), Short Form-12
(SF-12) and a supplementary patient satisfaction survey three months
pre-operatively and six months post-operatively.Aims
Patients and Methods
We present a case series of five patients who had revision surgery
following magnetic controlled growing rods (MGCR) for early onset
scoliosis. Metallosis was found during revision in four out of five
patients and we postulated a mechanism for rod failure based on
retrieval analysis. Retrieval analysis was performed on the seven explanted rods.
The mean duration of MCGR from implantation to revision was 35 months
(17 to 46). The mean age at revision was 12 years (7 to 15; four
boys, one girl).Aims
Patients and Methods
The high revision rates of the DePuy Articular Surface Replacement (ASR) and the DePuy ASR XL (the total hip arthroplasty (THA) version) have led to questions over the viability of metal-on-metal (MoM) hip joints. Some designs of MoM hip joint do, however, have reasonable mid-term performance when implanted in appropriate patients. Investigations into the reasons for implant failure are important to offer help with the choice of implants and direction for future implant designs. One way to assess the performance of explanted hip prostheses is to measure the wear (in terms of material loss) on the joint surfaces. In this study, a coordinate measuring machine (CMM) was used to measure the wear on five failed cementless Biomet Magnum/ReCap/ Taperloc large head MoM THAs, along with one Biomet ReCap resurfacing joint. Surface roughness measurements were also taken. The reason for revision of these implants was pain and/or adverse reaction to metal debris (ARMD) and/or elevated blood metal ion levels.Objectives
Methods
Demineralised bone matrix (DBM) is rarely used for the local
delivery of prophylactic antibiotics. Our aim, in this study, was
to show that a graft with a bioactive glass and DBM combination,
which is currently available for clinical use, can be loaded with
tobramycin and release levels of antibiotic greater than the minimum
inhibitory concentration for Antibiotic was loaded into a graft and subsequently evaluated
for drug elution kinetics and the inhibition of bacterial growth.
A rat femoral condylar plug model was used to determine the effect
of the graft, loaded with antibiotic, on bone healing.Aims
Materials and Methods
The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. Coronal T1ρ and T2 mapping and three-dimensional gradient-echo images were obtained from 20 subjects with medial knee osteoarthritis. We set the regions of interest (ROIs) on the full-thickness cartilage of the medial femoral condyle (MFC) and medial tibial plateau (MTP) of the knee and measured the cartilage thickness (mm) and T1ρ and T2 relaxation times (ms). Statistical analysis of time-dependent changes in the cartilage thickness and the T1ρ and T2 relaxation times was performed using one-way analysis of variance, and Scheffe’s test was employed for Objectives
Methods
Tissue responses to debris formed by abrasion of polymethylmethacrylate
(PMMA) spacers at two-stage revision arthroplasty for prosthetic
joint infection are not well described. We hypothesised that PMMA
debris induces immunomodulation in periprosthetic tissues. Samples of tissue were taken during 35 two-stage revision arthroplasties
(nine total hip and 26 total knee arthroplasties) in patients whose
mean age was 67 years (44 to 85). Fourier transform infrared microscopy
was used to confirm the presence of PMMA particles. Histomorphometry
was performed using Sudan Red and Haematoxylin-Eosin staining.
CD-68, CD-20, CD-11(c), CD-3 and IL-17 antibodies were used to immunophenotype
the inflammatory cells. All slides were scored semi-quantitatively
using the modified Willert scoring system.Aims
Patients and Methods
The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle. Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle.Objectives
Materials and Methods
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. 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.Objectives
Methods
Due to the complex anatomy of the pelvis, limb-sparing resections
of pelvic tumours achieving adequate surgical margins, can often
be difficult. The advent of computer navigation has improved the
precision of resection of these lesions, though there is little
evidence comparing resection with or without the assistance of navigation. Our aim was to evaluate the efficacy of navigation-assisted surgery
for the resection of pelvic bone tumours involving the posterior
ilium and sacrum. Using our prospectively updated institutional database, we conducted
a retrospective case control study of 21 patients who underwent
resection of the posterior ilium and sacrum, for the treatment of
a primary sarcoma of bone, between 1987 and 2015. The resection
was performed with the assistance of navigation in nine patients
and without navigation in 12. We assessed the accuracy of navigation-assisted
surgery, as defined by the surgical margin and how this affects
the rate of local recurrence, the disease-free survival and the
effects on peri-and post-operative morbidity. Aims
Patients and Methods
The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student Objectives
Methods
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.
The aims of this study were to compare the diagnostic test characteristics
of ultrasound alone, metal artefact reduction sequence MRI (MARS-MRI)
alone, and ultrasound combined with MARS-MRI for identifying intra-operative
pseudotumours in metal-on-metal hip resurfacing (MoMHR) patients
undergoing revision surgery. This retrospective diagnostic accuracy study involved 39 patients
(40 MoMHRs). The time between imaging modalities was a mean of 14.6
days (0 to 90), with imaging performed at a mean of 5.3 months (0.06
to 12) before revision. The prevalence of intra-operative pseudotumours
was 82.5% (n = 33).Aims
Methods
Chronic osteomyelitis may recur if dead space management, after
excision of infected bone, is inadequate. This study describes the
results of a strategy for the management of deep bone infection
and evaluates a new antibiotic-loaded biocomposite in the eradication
of infection from bone defects. We report a prospective study of 100 patients with chronic osteomyelitis,
in 105 bones. Osteomyelitis followed injury or surgery in 81 patients.
Nine had concomitant septic arthritis. 80 patients had comorbidities
(Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a
single-stage protocol including debridement, multiple sampling,
culture-specific systemic antibiotics, stabilisation, dead space
filling with the biocomposite and primary skin closure. Aims
Patients and Methods
Infection is a leading indication for revision
arthroplasty. Established criteria used to diagnose prosthetic joint infection
(PJI) include a range of laboratory tests. Leucocyte esterase (LE)
is widely used on a colorimetric reagent strip for the diagnosis
of urinary tract infections. This inexpensive test may be used for
the diagnosis or exclusion of PJI. Aspirates from 30 total hip arthroplasties
(THAs) and 79 knee arthroplasties (KA) were analysed for LE activity. Semi-quantitative
reagent strip readings of 15, 70, 125 and 500 white blood cells
(WBC) were validated against a manual synovial white cell count
(WCC). A receiver operating characteristic (ROC) curve was constructed
to determine the optimal cut-off point for the semi-quantitative
results. Based on established criteria, six THAs and 15 KAs were
classified as infected. The optimal cut-off point for the diagnosis
of PJI was 97 WBC. The closest semi-quantitative reading for a positive
result was 125 WBC, achieving a sensitivity of 81% and a specificity
of 93%. The positive and negative predictive values of the LE test
strip were 74% and 95% respectively. The LE reagent strip had a high specificity and negative predictive
value. A negative result may exclude PJI and negate the need for
further diagnostic tests. Cite this article:
Recently, several synovial biomarkers have been introduced into
the algorithm for the diagnosis of a prosthetic joint infection
(PJI). Alpha defensin is a promising biomarker, with a high sensitivity
and specificity, but it is expensive. Calprotectin is a protein
that is present in the cytoplasm of neutrophils, is released upon
neutrophil activation and exhibits anti-microbial activity. Our
aim, in this study, was to determine the diagnostic potential of
synovial calprotectin in the diagnosis of a PJI. In this pilot study, we prospectively collected synovial fluid
from the hip, knee, shoulder and elbow of 19 patients with a proven
PJI and from a control group of 42 patients who underwent revision
surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria
of the Musculoskeletal Infection Society. Synovial fluid was centrifuged
and the supernatant was used to measure the level of calprotectin
after applying a lateral flow immunoassay. Aims
Patients and Methods