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.
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
Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.Objectives
Method
Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells.Objectives
Methods
We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.Objectives
Materials and Methods
Post-operative migration of cemented acetabular components as
measured by radiostereometric analysis (RSA) has a strong predictive
power for late, aseptic loosening. Also, radiolucent lines predict
late loosening. Migration has been reduced by systemic bisphosphonate
treatment in randomised trials of hip and knee arthroplasty. Used
as a local treatment, a higher local dose of bisphosphonate can
be achieved without systemic exposure. We wished to see if this
principle could be applied usefully in total hip arthroplasty (THA). In this randomised placebo-controlled, double-blinded trial with
60 participants, we compressed gauze soaked in bisphosphonate solution
(ibandronate) or saline against the acetabular bone bed immediately
before cementing the acetabular component. RSA, classification of
radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters
Universities Osteoarthritis Index (WOMAC) were carried out at three-,
six-, 12-, and 24-month follow-up.Aims
Patients and Methods
Patellar instability most frequently presents
during adolescence. Congenital and infantile dislocation of the
patella is a distinct entity from adolescent instability and measurable
abnormalities may be present at birth. In the normal patellofemoral
joint an increase in quadriceps angle and patellar height are matched
by an increase in trochlear depth as the joint matures. Adolescent
instability may herald a lifelong condition leading to chronic disability
and arthritis. Restoring normal anatomy by trochleoplasty, tibial tubercle transfer
or medial patellofemoral ligament (MPFL) reconstruction in the young
adult prevents further instability. Although these techniques are
proven in the young adult, they may cause growth arrest and deformity
where the physis is open. A vigorous non-operative strategy may
permit delay of surgery until growth is complete. Where non-operative
treatment has failed a modified MPFL reconstruction may be performed
to maintain stability until physeal closure permits anatomical reconstruction.
If significant growth remains an extraosseous reconstruction of
the MPFL may impart the lowest risk to the physis. If minor growth
remains image intensifier guided placement of femoral intraosseous
fixation may impart a small, but acceptable, risk to the physis. This paper presents and discusses the literature relating to
adolescent instability and provides a framework for management of
these patients. Cite this article:
There remains conflicting evidence regarding cortical bone strength
following bisphosphonate therapy. As part of a study to assess the
effects of bisphosphonate treatment on the healing of rat tibial
fractures, the mechanical properties and radiological density of
the uninjured contralateral tibia was assessed. Skeletally mature aged rats were used. A total of 14 rats received
1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium
chloride (control) daily. Stress at failure and toughness of the
tibial diaphysis were calculated following four-point bending tests.Objectives
Methods
Our aim was to investigate the predictive factors for the development
of a rebound phenomenon after temporary hemiepiphysiodesis in children
with genu valgum. We studied 37 limbs with idiopathic genu valgum who were treated
with hemiepiphyseal stapling, and with more than six months remaining
growth at removal of the staples. All children were followed until
skeletal maturity or for more than two years after removal of the
staples.Aims
Patients and 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
Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) Objectives
Materials and 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.
Fracture repair occurs by two broad mechanisms:
direct healing, and indirect healing with callus formation. The effects
of bisphosphonates on fracture repair have been assessed only in
models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised
tibial osteotomy was used. Ten skeletally mature Sprague–Dawley
rats received daily subcutaneous injections of 1 µg/kg ibandronate
(IBAN) and ten control rats received saline (control). Three weeks
later a tibial osteotomy was rigidly fixed with compression plating.
Six weeks later the animals were killed. Fracture repair was assessed
with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly
lower in the IBAN group compared with controls (8.69 Nmm-2 ( Bisphosphonate treatment in a therapeutic dose, as used for risk
reduction in fragility fractures, had an inhibitory effect on direct
fracture healing. We propose that bisphosphonate therapy not be
commenced until after the fracture has united if the fracture has
been rigidly fixed and is undergoing direct osteonal healing. Cite this article:
To assess the extent of osteointegration in two designs of shoulder
resurfacing implants. Bony integration to the Copeland cylindrical
central stem design and the Epoca RH conical-crown design were compared. Implants retrieved from six patients in each group were pair-matched.
Mean time to revision surgery of Copeland implants was 37 months
(standard deviation (Aims
Patients and Methods
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. Primary human osteoblasts in Objectives
Methods
To quantify and compare peri-acetabular bone mineral density
(BMD) between a monoblock acetabular component using a metal-on-metal
(MoM) bearing and a modular titanium shell with a polyethylene (PE)
insert. The secondary outcome was to measure patient-reported clinical
function. A total of 50 patients (25 per group) were randomised to MoM
or metal-on-polyethlene (MoP). There were 27 women (11 MoM) and
23 men (14 MoM) with a mean age of 61.6 years (47.7 to 73.2). Measurements
of peri-prosthetic acetabular and contralateral hip (covariate)
BMD were performed at baseline and at one and two years’ follow-up.
The Western Ontario and McMaster Universities osteoarthritis index
(WOMAC), University of California, Los Angeles (UCLA) activity score,
Harris hip score, and RAND-36 were also completed at these intervals.Objectives
Methods
Many different lengths of stem are available
for use in primary total hip replacement, and the morphology of
the proximal femur varies greatly. The more recently developed shortened
stems provide a distribution of stress which closely mimics that
of the native femur. Shortening the femoral component potentially
comes at the cost of decreased initial stability. Clinical studies
on the performance of shortened cemented and cementless stems are promising,
although long-term follow-up studies are lacking. We provide an
overview of the current literature on the anatomical features of
the proximal femur and the biomechanical aspects and clinical outcomes
associated with the length of the femoral component in primary hip
replacement, and suggest a classification system for the length
of femoral stems. Cite this article:
We evaluated the impact of lumbar instrumented
circumferential fusion on the development of adjacent level vertebral
compression fractures (VCFs). Instrumented posterior lumbar interbody
fusion (PLIF) has become a popular procedure for degenerative lumbar
spine disease. The immediate rigidity produced by PLIF may cause
more stress and lead to greater risk of adjacent VCFs. However,
few studies have investigated the relationship between PLIF and
the development of subsequent adjacent level VCFs. Between January 2005 and December 2009, a total of 1936 patients
were enrolled. Of these 224 patients had a new VCF and the incidence
was statistically analysed with other covariants. In total 150 (11.1%)
of 1348 patients developed new VCFs with PLIF, with 108 (72%) cases
at adjacent segment. Of 588 patients, 74 (12.5%) developed new subsequent
VCFs with conventional posterolateral fusion (PLF), with 37 (50%)
patients at an adjacent level. Short-segment fusion, female and
age older than 65 years also increased the development of new adjacent
VCFs in patients undergoing PLIF. In the osteoporotic patient, more
rigid fusion and a higher stress gradient after PLIF will cause
a higher adjacent VCF rate. Cite this article:
