The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.Objectives
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:
Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking.
The aim of this study was to evaluate antegrade autologous bone
grafting with the preservation of articular cartilage in the treatment
of symptomatic osteochondral lesions of the talus with subchondral
cysts. The study involved seven men and five women; their mean age was
35.9 years (14 to 70). All lesions included full-thickness articular
cartilage extending through subchondral bone and were associated
with subchondral cysts. Medial lesions were exposed through an oblique
medial malleolar osteotomy, and one lateral lesion was exposed by
expanding an anterolateral arthroscopic portal. After refreshing
the subchondral cyst, it was grafted with autologous cancellous
bone from the distal tibial metaphysis. The fragments of cartilage
were fixed with 5-0 nylon sutures to the surrounding cartilage.
Function was assessed at a mean follow-up of 25.3 months (15 to
50), using the American Orthopaedic Foot and Ankle Society (AOFAS)
ankle-hindfoot outcome score. The radiological outcome was assessed
using MRI and CT scans.Aims
Patients and Methods
The primary aim of this study was to determine the morbidity
of a tibial strut autograft and characterize the rate of bony union
following its use. We retrospectively assessed a series of 104 patients from a single
centre who were treated with a tibial strut autograft of > 5 cm
in length. A total of 30 had a segmental reconstruction with continuity
of bone, 27 had a segmental reconstruction without continuity of
bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity
was defined as any event that required a modification of the postoperative
management. Union was assessed clinically and radiologically at
a median of 36 months (IQR, 14 to 74).Aims
Patients and Methods
Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.Objectives
Methods
The objective of this study was to investigate bone healing after
internal fixation of displaced femoral neck fractures (FNFs) with
the Dynamic Locking Blade Plate (DLBP) in a young patient population
treated by various orthopaedic (trauma) surgeons. We present a multicentre prospective case series with a follow-up
of one year. All patients aged ≤ 60 years with a displaced FNF treated
with the DLBP between 1st August 2010 and December 2014 were included.
Patients with pathological fractures, concomitant fractures of the
lower limb, symptomatic arthritis, local infection or inflammation,
inadequate local tissue coverage, or any mental or neuromuscular
disorder were excluded. Primary outcome measure was failure in fracture
healing due to nonunion, avascular necrosis, or implant failure
requiring revision surgery.Aims
Patients and Methods
This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s Objectives
Methods
The Bereiter trochleoplasty has been used in our unit for 12
years to manage recurrent patellar instability in patients with
severe trochlea dysplasia. The aim of this study was to document
the outcome of a large consecutive cohort of patients who have undergone
this operation. Between June 2002 and August 2013, 214 consecutive trochleoplasties
were carried out in 185 patients. There were 133 women and 52 men
with a mean age of 21.3 years (14 to 38). All patients were offered
yearly clinical and radiological follow-up. They completed the following
patient reported outcome scores (PROMs): International Knee Documentation
Committee subjective scale, the Kujala score, the Western Ontario
and McMaster Universities Arthritis Index score and the short-form
(SF)-12. Aims
Patients and Methods
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.
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:
The anterior pelvic internal fixator is increasingly used for
the treatment of unstable, or displaced, injuries of the anterior
pelvic ring. The evidence for its use, however, is limited. The
aim of this paper is to describe the indications for its use, how
it is applied and its complications. We reviewed the case notes and radiographs of 50 patients treated
with an anterior pelvic internal fixator between April 2010 and
December 2015 at a major trauma centre in the United Kingdom. The
median follow-up time was 38 months (interquartile range 24 to 51).Aims
Patients and Methods
Resection of the proximal humerus for the primary malignant bone
tumour sometimes requires We reviewed 45 patients who had undergone resection of a primary
malignant tumour of the proximal humerus. There were 29 in the deltoid
sparing group and 16 in the deltoid resecting group. Imaging studies
were reviewed to assess tumour extension and soft-tissue involvement.
The presence of a fat rim separating the tumour from the deltoid
on MRI was particularly noted. The cumulative probability of local
recurrence was calculated in a competing risk scenario.Aims
Patients and Methods
The aim of this prospective study was to evaluate the intermediate-term
outcomes after revision anatomical ankle ligament reconstruction
augmented with suture tape for a failed modified Broström procedure. A total of 30 patients with persistent instability of the ankle
after a Broström procedure underwent revision augmented with suture
tape. Of these, 24 patients who were followed up for more than two
years were included in the study. There were 13 men and 11 women.
Their mean age was 31.8 years (23 to 44). The mean follow-up was 38.5
months (24 to 56) The clinical outcome was assessed using the Foot
and Ankle Outcome Score (FAOS) and the Foot and Ankle Ability Measure
(FAAM) score. The stability of the ankle was assessed using stress
radiographs.Aims
Patients and Methods
The aim of this study was to compare the outcome of revision
total knee arthroplasty (TKA) with and without proximalisation of
the tibial tubercle in patients with a failed primary TKA who have
pseudo patella baja. All revision TKAs, performed between January 2008 and November
2013 at a tertiary referral University Orthopaedic Department were
retrospectively reviewed. Pseudo patella baja was defined using
the modified Insall-Salvati and the Blackburne-Peel ratios. A proximalisation
of the tibial tubercle was performed in 13 patients with pseudo
patella baja who were matched with a control group of 13 patients
for gender, age, height, weight, body mass index, length of surgery
and Blackburne-Peel ratio. Outcome was assessed two years post-operatively
using the Knee Society Score (KSS).Aims
Patients and Methods
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:
The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium Objectives
Methods
This retrospective cohort study compared the results of vascularised
and non-vascularised anterior sliding tibial grafts for the treatment
of osteoarthritis (OA)of the ankle secondary to osteonecrosis of
the talus. We reviewed the clinical and radiological outcomes of 27 patients
who underwent arthrodesis with either vascularised or non-vascularised
(conventional) grafts, comparing the outcomes (clinical scores,
proportion with successful union and time to union) between the
two groups. The clinical outcome was assessed using the Mazur and
American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot
scores. The mean follow-up was 35 months (24 to 68).Aims
Patients and 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
