The ageing population and an increase in both
the incidence and prevalence of cancer pose a healthcare challenge, some
of which is borne by the orthopaedic community in the form of osteoporotic
fractures and metastatic bone disease. In recent years there has
been an increasing understanding of the pathways involved in bone
metabolism relevant to osteoporosis and metastases in bone. Newer
therapies may aid the management of these problems. One group of
drugs, the antibody mediated anti-resorptive therapies (AMARTs)
use antibodies to block bone resorption pathways. This review seeks
to present a synopsis of the guidelines, pharmacology and potential pathophysiology
of AMARTs and other new anti-resorptive drugs. We evaluate the literature relating to AMARTs and new anti-resorptives
with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for
Nuclear Factor Kappa-B Ligand. It is the first AMART approved by
the National Institute for Health and Clinical Excellence and the
US Food and Drug Administration. Other novel anti-resorptives awaiting
approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and
prevention of the complications of bone metastases. Recent evidence
suggests, however, that denosumab may have an adverse event profile
similar to bisphosphonates, including atypical femoral fractures.
It is, therefore, essential that orthopaedic surgeons are conversant
with these medications and their safe usage. Take home message: Denosumab has important orthopaedic indications
and has been shown to significantly reduce patient morbidity in
osteoporosis and metastatic bone disease. Cite this article:
Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay.Objectives
Methods
The major problem with repair of an articular cartilage injury
is the extensive difference in the structure and function of regenerated,
compared with normal cartilage. Our work investigates the feasibility
of repairing articular osteochondral defects in the canine knee
joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate
(ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells
(BMSCs) and assesses its biological compatibility. The bone–cartilage scaffold was prepared as a laminated composite,
using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer
of polylactic acid–hydroxyacetic acid as the bony scaffold, and
sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous
scaffold. Ten-to 12-month-old hybrid canines were randomly divided
into an experimental group and a control group. BMSCs were obtained
from the iliac crest of each animal, and only those of the third
generation were used in experiments. An articular osteochondral
defect was created in the right knee of dogs in both groups. Those
in the experimental group were treated by implanting the composites
consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs.
Those in the control group were left untreated.Objectives
Methods
Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.Objectives
Materials and Methods
After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing.Objectives
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
Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.Objectives
Methods
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
To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed Objectives
Methods
The purpose of this study was to evaluate the
expression of acid-sensing ion channels (ASICs) in the capsule and synovial
fluid of patients with frozen shoulder. Capsular tissue and synovial
fluid were obtained from 18 patients with idiopathic frozen shoulder
(FS group) and 18 patients with instability of the shoulder (control
group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule
were determined using the reverse transcriptase-polymerase chain
reaction, immunoblot analysis, and immunohistochemistry (IHC). The
concentrations in synovial fluid were evaluated using an enzyme-linked
immunosorbent assay. The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule
were significantly increased in the FS group compared with the control
group. The protein levels of these three ASICs were also increased.
The increased expressions were confirmed by IHC. Of the ASICs, ASIC3
showed the greatest increase in both mRNA and levels of expression
compared with the control group. The levels of ASIC1 and ASIC3 in
synovial fluid were significantly increased in the FS group. This study suggests that ASICs may play a role as mediators of
inflammatory pain and be involved in the pathogenesis of frozen
shoulder. Cite this article:
This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing. A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation.Objectives
Materials and Methods
Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1.Objectives
Materials and Methods
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.Objectives
Methods
The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models. A systematic literature search up to May 2015 was carried out using the PubMed, Ovid, EBM reviews, ISI Web of Science, EBSCO, CBM, CNKI databases with the term and boolean operators: statins and osteonecrosis in all fields. Risk ratio (RR), as the risk estimate of specific outcome, was calculated along with 95% confidence intervals (CI). The methodological quality of individual studies was assessed using a quantitative tool based on the updated Stroke Therapy Academic Industry Roundtable (STAIR) recommendations.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
Treatment for osteoarthritis (OA) has traditionally
focused on joint replacement for end-stage disease. An increasing number
of surgical and pharmaceutical strategies for disease prevention
have now been proposed. However, these require the ability to identify
OA at a stage when it is potentially reversible, and detect small
changes in cartilage structure and function to enable treatment
efficacy to be evaluated within an acceptable timeframe. This has
not been possible using conventional imaging techniques but recent
advances in musculoskeletal imaging have been significant. In this
review we discuss the role of different imaging modalities in the
diagnosis of the earliest changes of OA. The increasing number of
MRI sequences that are able to non-invasively detect biochemical
changes in cartilage that precede structural damage may offer a
great advance in the diagnosis and treatment of this debilitating
condition. Cite this article:
The objective of this double-blind randomised controlled trial
was to assess whether ultrasound guidance improved the efficacy
of corticosteroid injections for Morton’s neuroma (MN). In all, 50 feet (40 patients) were recruited for this study but
five feet were excluded due to the patients declining further participation.
The mean age of the remaining 36 patients (45 feet) was 57.8 years
(standard deviation (Aims
Patients and Methods
The purpose of this article is to provide the
reader with a seven-step checklist that could help in minimising
the risk of PJI. The check list includes strategies that can be
implemented pre-operatively such as medical optimisation, and reduction
of the bioburden by effective skin preparation or actions taking
during surgery such as administration of timely and appropriate
antibiotics or blood conservation, and finally implementation of
post-operative protocols such as efforts to minimise wound drainage
and haematoma formation. Cite this article:
This animal study compares different methods
of performing an osteotomy, including using an Erbium-doped Yttrium
Aluminum Garnet laser, histologically, radiologically and biomechanically.
A total of 24 New Zealand rabbits were divided into four groups
(Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical
saw blade and Group IV: laser). A proximal transverse diaphyseal
osteotomy was performed on the right tibias of the rabbits after the
application of a circular external fixator. The rabbits were killed
six weeks after the procedure, the operated tibias were resected
and radiographs taken. The specimens were tested biomechanically using three-point bending
forces, and four tibias from each group were examined histologically.
Outcome parameters were the biomechanical stability of the tibias
as assessed by the failure to load and radiographic and histological
examination of the osteotomy site. The osteotomies healed in all specimens both radiographically
and histologically. The differences in the mean radiographic (p
= 0.568) and histological (p = 0.71) scores, and in the mean failure
loads (p = 0.180) were not statistically significant between the
groups. Different methods of performing an osteotomy give similar quality
of union. The laser osteotomy, which is not widely used in orthopaedics
is an alternative to the current methods. Cite this article:
We describe a case of bilateral weakness of the lower limbs, sensory disturbance and intermittent urinary incontinence, secondary to untreated Gitelman’s syndrome, in a 42-year-old female who was referred with presumed cauda equina syndrome. On examination, the power of both legs was uniformly reduced, and the perianal and lower-limb sensation was altered. However, MRI of the lumbar spine was normal. Measurements of serum and urinary potassium were low and blood gas analysis revealed metabolic alkalosis. Her symptoms resolved following potassium replacement. We emphasise the importance of measurement of the plasma and urinary levels of electrolytes in the investigation of patients with paralysis of the lower limbs and suggest that they, together with blood gas analysis, allow the exclusion of unusual causes of muscle weakness resulting from metabolic disorders such as metabolic alkalosis.
