Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.Objectives
Methods
The aim of this study was to examine whether asymmetric loading
influences macrophage elastase (MMP12) expression in different parts
of a rat tail intervertebral disc and growth plate and if MMP12
expression is correlated with the severity of the deformity. A wedge deformity between the ninth and tenth tail vertebrae
was produced with an Ilizarov-type mini external fixator in 45 female
Wistar rats, matched for their age and weight. Three groups were
created according to the degree of deformity (10°, 30° and 50°).
A total of 30 discs and vertebrae were evaluated immunohistochemically
for immunolocalisation of MMP12 expression, and 15 discs were analysed
by western blot and zymography in order to detect pro- and active
MMP12.Objectives
Methods
Corticosteroid use has been implicated in the
development of osteonecrosis of the femoral head (ONFH). The exact mechanism
and predisposing factors such as age, gender, dosage, type and combination
of steroid treatment remain controversial. Between March and July
2003, a total of 539 patients with severe acute respiratory syndrome (SARS)
were treated with five different types of steroid. There were 129
men (24%) and 410 women (76%) with a mean age of 33.7 years (21
to 59). Routine screening was undertaken with radiographs, MRI and/or
CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed
as suffering from ONFH, compared with only 79 of 410 female patients
(19.3%). The incidence of ONFH in the patients aged between 20 and
49 years was much higher than that of the group aged between 50
and 59 years (25.9% (127 of 491) Cite this article:
Periprosthetic joint infection (PJI) is a devastating
complication for patients and results in greatly increased costs
of care for both healthcare providers and patients. More than 15
500 revision hip and knee procedures were recorded in England, Wales
and Northern Ireland in 2013, with infection accounting for 13%
of revision hip and 23% of revision knee procedures. We report our experience of using antibiotic eluting absorbable
calcium sulphate beads in 15 patients (eight men and seven women
with a mean age of 64.8 years; 41 to 83) as part of a treatment
protocol for PJI in revision arthroplasty. The mean follow-up was 16 months (12 to 22). We report the outcomes
and complications, highlighting the risk of hypercalcaemia which
occurred in three patients. We recommend that serum levels of calcium be routinely sought
following the implantation of absorbable calcium sulphate beads
in orthopaedic surgery. Cite this article:
This study evaluated whether obese patients who
lost weight before their total joint replacement and kept it off post-operatively
were at lower risk of surgical site infection (SSI) and re-admission
compared with those who remained the same weight. We reviewed 444 patients who underwent a total hip replacement
and 937 with a total knee replacement who lost weight pre-operatively
and sustained their weight loss after surgery. After adjustments,
patients who lost weight before a total hip replacement and kept
it off post-operatively had a 3.77 (95% confidence interval (CI)
1.59 to 8.95) greater likelihood of deep SSIs and those who lost
weight before a total knee replacement had a 1.63 (95% CI 1.16 to
2.28) greater likelihood of re-admission compared with the reference
group. These findings raise questions about the safety of weight management
before total replacement of the hip and knee joints. 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 August 2015 Trauma Roundup360 looks at: Thromboprophylaxis not required in lower limb fractures; Subclinical thyroid dysfunction and fracture risk: moving the boundaries in fracture; Posterior wall fractures refined; Neurological injury and acetabular fracture surgery; Posterior tibial plateau fixation; Tibial plateau fractures in the longer term; Comprehensive orthogeriatric care and hip fracture; Compartment syndrome: in the eye of the beholder?
Wrist block has been used to provide pain relief
for many procedures on the hand and wrist but its role in arthroscopy
of the wrist remains unexplored. Chondrotoxicity has been a concern
with the intra-articular infiltration of local anaesthetic. We aimed
to evaluate and compare the analgesic effect of portal and wrist
joint infiltration with a wrist block on the pain experienced by
patients after arthroscopy of the wrist. A prospective, randomised, double-blind trial was designed and
patients undergoing arthroscopy of the wrist under general anaesthesia
as a day case were recruited for the study. Levo-bupivacaine was
used for both techniques. The effects were evaluated using a ten-point
visual analogue scale, and the use of analgesic agents was also
compared. The primary outcomes for statistical analyses were the
mean pain scores and the use of analgesia post-operatively. A total of 34 patients (63% females) were recruited to the portal
and joint infiltration group and 32 patients (59% males) to the
wrist block group. Mean age was 40.8 years in the first group and
39.7 years in the second group (p >
0.05). Both techniques provided
effective pain relief in the first hour and 24 hours post-operatively
but wrist block gave better pain scores at bedtime on the day of
surgery (p = 0.007) and at 24 hours post-operatively (p = 0.006). Wrist block provides better and more reliable analgesia in patients
undergoing arthroscopy of the wrist without exposing patients to
the risk of chondrotoxicity. Cite this article:
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:
MicroRNAs (miRNAs ) are small non-coding RNAs
that regulate gene expression. We hypothesised that the functions
of certain miRNAs and changes to their patterns of expression may
be crucial in the pathogenesis of nonunion. Healing fractures and
atrophic nonunions produced by periosteal cauterisation were created
in the femora of 94 rats, with 1:1 group allocation. At post-fracture
days three, seven, ten, 14, 21 and 28, miRNAs were extracted from
the newly generated tissue at the fracture site. Microarray and
real-time polymerase chain reaction (PCR) analyses of day 14 samples
revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p, were highly upregulated in nonunion.
Real-time PCR analysis further revealed that, in nonunion, the expression
levels of all five of these miRNAs peaked on day 14 and declined
thereafter. Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p,
miR-146b-5p and miR-223-3p may play an important role in the development
of nonunion. These findings add to the understanding of the molecular mechanism
for nonunion formation and may lead to the development of novel
therapeutic strategies for its treatment. Cite this article:
This Although many agents commonly injected into joints are chondrotoxic,
in this Cite this article:
We measured the plasma 25-hydroxyvitamin D3 (25(OH)D3) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.
The February 2015 Research Roundup360 looks at: Markers of post-traumatic ankle arthritis; Mangoes, trees and Solomon Islanders; Corticosteroid injection and ulnar neuropathy; Moral decision-making: the secret skill?; Biomechanical studies under the spotlight; Anaesthetic risk and hip replacement
Drug therapy forms an integral part of the management
of many orthopaedic conditions. However, many medicines can produce
serious adverse reactions if prescribed inappropriately, either
alone or in combination with other drugs. Often these hazards are
not appreciated. In response to this, the European Union recently
issued legislation regarding safety measures which member states
must adopt to minimise the risk of errors of medication. In March 2014 the Medicines and Healthcare products Regulatory
Agency and NHS England released a Patient Safety Alert initiative
focussed on errors of medication. There have been similar initiatives
in the United States under the auspices of The National Coordinating
Council for Medication Error and The Joint Commission on the Accreditation
of Healthcare Organizations. These initiatives have highlighted
the importance of informing and educating clinicians. Here, we discuss common drug interactions and contra-indications
in orthopaedic practice. This is germane to safe and effective clinical
care. Cite this article:
Ligaments which heal spontaneously have a healing process that
is similar to skin wound healing. Menopause impairs skin wound healing
and may likewise impair ligament healing. Our purpose in this study
was to investigate the effect of surgical menopause on ligament
healing in a rabbit medial collateral ligament model. Surgical menopause was induced with ovariohysterectomy surgery
in adult female rabbits. Ligament injury was created by making a
surgical gap in the midsubstance of the medial collateral ligament.
Ligaments were allowed to heal for six or 14 weeks in the presence
or absence of oestrogen before being compared with uninjured ligaments. Molecular
assessment examined the messenger ribonucleic acid levels for collagens,
proteoglycans, proteinases, hormone receptors, growth factors and
inflammatory mediators. Mechanical assessments examined ligament
laxity, total creep strain and failure stress.Objectives
Methods
Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.
Femoroacetabular Junction Impingement (FAI) describes abnormalities
in the shape of the femoral head–neck junction, or abnormalities
in the orientation of the acetabulum. In the short term, FAI can
give rise to pain and disability, and in the long-term it significantly increases
the risk of developing osteoarthritis. The Femoroacetabular Impingement
Trial (FAIT) aims to determine whether operative or non-operative
intervention is more effective at improving symptoms and preventing
the development and progression of osteoarthritis. FAIT is a multicentre superiority parallel two-arm randomised
controlled trial comparing physiotherapy and activity modification
with arthroscopic surgery for the treatment of symptomatic FAI.
Patients aged 18 to 60 with clinical and radiological evidence of
FAI are eligible. Principal exclusion criteria include previous
surgery to the index hip, established osteoarthritis (Kellgren–Lawrence
≥ 2), hip dysplasia (centre-edge angle <
20°), and completion
of a physiotherapy programme targeting FAI within the previous 12
months. Recruitment will take place over 24 months and 120 patients
will be randomised in a 1:1 ratio and followed up for three years.
The two primary outcome measures are change in hip outcome score
eight months post-randomisation (approximately six-months post-intervention
initiation) and change in radiographic minimum joint space width
38 months post-randomisation. ClinicalTrials.gov: NCT01893034. Cite this article: Aims
Methods
Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.
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:
Total knee arthroplasty (TKA) is known to lead
to a reduction in periprosthetic bone mineral density (BMD). In theory,
this may lead to migration, instability and aseptic loosening of
the prosthetic components. Bisphosphonates inhibit bone resorption
and may reduce this loss in BMD. We hypothesised that treatment
with bisphosphonates and calcium would lead to improved BMD and
clinical outcomes compared with treatment with calcium supplementation
alone following TKA. A total of 26 patients, (nine male and 17 female,
mean age 67 years) were prospectively randomised into two study
groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium
only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA)
measurements were performed post-operatively, and at three months,
six months, one, two, four, and seven years post-operatively. Mean femoral metaphyseal BMD was significantly higher in the
bisphosphonate group compared with controls, up to four years following
surgery in some areas of the femur (p = 0.045). BMD was observed
to increase in the lateral tibial metaphysis in the bisphosphonate
group until seven years (p = 0.002), and was significantly higher than
that observed in the control group throughout (p = 0.024). There
were no significant differences between the groups in the central
femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions
of interest (ROI) of either the femur or tibia. Bisphosphonate treatment after TKA may be of benefit for patients
with poor bone quality. However, further studies with a larger number
of patients are necessary to assess whether this is clinically beneficial. Cite this article: