The development and pre-clinical evaluation of
nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated
with titanium dioxide (TiO. 2. ) nanotube arrays is reviewed. In
vitro and in vivo evaluations show that
TiO. 2. nanotubes on Ti surfaces positively affect the osseointegration,
cell differentiation,
Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Human ADMSCs were cultured in medium supplemented with HPL, Hplasma and a combination of HPL and Hplasma (HPL+Hplasma). Characteristics of these ADMSCs, including osteogenesis, were evaluated in comparison with those cultured in fetal bovine serum (FBS).Objectives
Methods
Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.Objectives
Methods
Objectives. Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. Methods. We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use. Results. Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.Objectives
Methods
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
Objectives. 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
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
The purpose of this retrospective study was to differentiate
between the MRI features of normal post-operative change and those
of residual or recurrent disease after intralesional treatment of
an atypical cartilage tumour (ACT)/grade I chondrosarcoma. We reviewed the case notes, radiology and histology of 75 patients,
who had been treated for an ACT/grade I chondrosarcoma by curettage,
phenolisation and bone allografting between 1994 and 2005. The first
post-operative Gd-enhanced MRI scan was carried out within one year
of surgery. Patients had a minimum of two scans and a mean follow-up
of 72 months (13 to 169). Further surgery was undertaken in cases
of suspected recurrence.Aims
Patients and 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
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 aimed to assess the influence of ethnicity on the incidence
of heterotopic ossification (HO) after total hip arthroplasty (THA). We studied the six-month post-operative anteroposterior radiographs
of 1449 consecutive primary THAs (1324 patients) and retrospectively
graded them for the presence of HO, using the Brooker Classification. 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
The purpose of this study was to evaluate A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted
subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm
PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight
and 12 weeks post-implantation were compared with control (Sham)
and PLAGA (five rats per group/point in time). Rats were observed
for signs of morbidity, overt toxicity, weight gain and food consumption,
while haematology, urinalysis and histopathology were completed
when the animals were killed.Objectives
Methods
Currently, there is no animal model in which
to evaluate the underlying physiological processes leading to the heterotopic
ossification (HO) which forms in most combat-related and blast wounds.
We sought to reproduce the ossification that forms under these circumstances
in a rat by emulating patterns of injury seen in patients with severe
injuries resulting from blasts. We investigated whether exposure
to blast overpressure increased the prevalence of HO after transfemoral
amputation performed within the zone of injury. We exposed rats
to a blast overpressure alone (BOP-CTL), crush injury and femoral
fracture followed by amputation through the zone of injury (AMP-CTL)
or a combination of these (BOP-AMP). The presence of HO was evaluated
using radiographs, micro-CT and histology. HO developed in none
of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats.
Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular
pathways of HO, the effect of varying intensities of blast overpressure,
and to evaluate new means of prophylaxis and treatment of heterotopic
ossification. Cite this article:
The management of children’s fractures has evolved
as a result of better health education, changes in lifestyle, improved
implant technology and the changing expectations of society. This
review focuses on the changes seen in paediatric fractures, including
epidemiology, the increasing problems of obesity, the mechanisms
of injury, non-accidental injuries and litigation. We also examine
the changes in the management of fractures at three specific sites:
the supracondylar humerus, femoral shaft and forearm. There has
been an increasing trend towards surgical stabilisation of these
fractures. The reasons for this are multifactorial, including societal
expectations of a perfect result and reduced hospital stay. Reduced hospital
stay is beneficial to the social, educational and psychological
needs of the child and beneficial to society as a whole, due to
reduced costs. Cite this article:
Conventional cemented acetabular components are
reported to have a high rate of failure when implanted into previously
irradiated bone. We recommend the use of a cemented reconstruction
with the addition of an acetabular reinforcement cross to improve
fixation. We reviewed a cohort of 45 patients (49 hips) who had undergone
irradiation of the pelvis and a cemented total hip arthroplasty
(THA) with an acetabular reinforcement cross. All hips had received
a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour
or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3:
45 to 60; mean: 49.57, 32 to 72). The mean follow-up after THA was 51 months (17 to 137). The cumulative
probability of revision of the acetabular component for a mechanical
reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60
months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One
hip was revised for mechanical failure and three for infection. Cemented acetabular components with a reinforcement cross provide
good medium-term fixation after pelvic irradiation. These patients
are at a higher risk of developing infection of their THA. Cite this article:
Cancellous allograft bone chips are commonly
used in the reconstruction of defects in bone after removal of benign tumours.
We investigated the MRI features of grafted bone chips and their
change over time, and compared them with those with recurrent tumour.
We retrospectively reviewed 66 post-operative MRIs from 34 patients
who had undergone curettage and grafting with cancellous bone chips
to fill the defect after excision of a tumour. All grafts showed
consistent features at least six months after grafting: homogeneous
intermediate or low signal intensities with or without scattered
hyperintense foci (speckled hyperintensities) on T1 images; high
signal intensities with scattered hypointense foci (speckled hypointensities)
on T2 images, and peripheral rim enhancement with or without central
heterogeneous enhancements on enhanced images. Incorporation of
the graft occurred from the periphery to the centre, and was completed
within three years. Recurrent lesions consistently showed the same signal
intensities as those of pre-operative MRIs of the primary lesions.
There were four misdiagnoses, three of which were chondroid tumours. We identified typical MRI features and clarified the incorporation
process of grafted cancellous allograft bone chips. The most important
characteristics of recurrent tumours were that they showed the same
signal intensities as the primary tumours. It might sometimes be
difficult to differentiate grafted cancellous allograft bone chips
from a recurrent chondroid tumour. Cite this article:
The aim of this experimental study on New Zealand’s white rabbits
was to investigate the transplantation of autogenous growth plate
cells in order to treat the injured growth plate. They were assessed
in terms of measurements of radiological tibial varus and histological
characteristics. An experimental model of plate growth medial partial resection
of the tibia in 14 New Zealand white rabbits was created. During
this surgical procedure the plate growth cells were collected and
cultured. While the second surgery was being performed, the autologous
cultured growth plate cells were grafted at the right tibia, whereas
the left tibia was used as a control group. Objectives
Methods
The pre-operative differentiation between enchondroma,
low-grade chondrosarcoma and high-grade chondrosarcoma remains a
diagnostic challenge. We reviewed the accuracy and safety of the
radiological grading of cartilaginous tumours through the assessment
of, first, pre-operative radiological and post-operative histological agreement,
and second the rate of recurrence in lesions confirmed as high-grade
on histology. We performed a retrospective review of major long
bone cartilaginous tumours managed by curettage as low grade between
2001 and 2012. A total of 53 patients with a mean age of 47.6 years
(8 to 71) were included. There were 23 men and 30 women. The tumours
involved the femur (n = 20), humerus (n = 18), tibia (n = 9), fibula
(n = 3), radius (n = 2) and ulna (n = 1). Pre-operative diagnoses
resulted from multidisciplinary consensus following radiological
review alone for 35 tumours, or with the addition of pre-operative
image guided needle biopsy for 18. The histologically confirmed diagnosis
was enchondroma for two (3.7%), low-grade chondrosarcoma for 49
(92.6%) and high-grade chondrosarcoma for two (3.7%). Three patients
with a low-grade tumour developed a local recurrence at a mean of 15
months (12 to 17) post-operatively. A single high-grade recurrence
(grade II) was treated with tibial diaphyseal replacement. The overall
recurrence rate was 7.5% at a mean follow-up of 4.7 years (1.2 to
12.3). Cartilaginous tumours identified as low-grade on pre-operative
imaging with or without additional image-guided needle biopsy can
safely be managed as low-grade without pre-operative histological
diagnosis. A few tumours may demonstrate high-grade features histologically,
but the rates of recurrence are not affected. Cite this article:
We hypothesised that the use of pulsed electromagnetic
field (PEMF) bone growth stimulation in acute scaphoid fractures
would significantly shorten the time to union and reduce the number
of nonunions in a randomised, double-blind, placebo-controlled multicentre
trial. A total of 102 patients (78 male, 24 female; mean age 35
years (18 to 77)) from five different medical centres with a unilateral
undisplaced acute scaphoid fracture were randomly allocated to PEMF
(n = 51) or placebo (n = 51) and assessed with regard to functional
and radiological outcomes (multiplanar reconstructed CT scans) at
6, 9, 12, 24 and 52 weeks. The overall time to clinical and radiological healing
did not differ significantly between the active PEMF group and the
placebo group. We concluded that the addition of PEMF bone growth
stimulation to the conservative treatment of acute scaphoid fractures
does not accelerate bone healing. Cite this article:
In this case study, we describe the clinical
presentation and treatment of 36 patients with periosteal chondrosarcoma
collected over a 59-year period by the archive of the Netherlands
Committee on Bone Tumours. The demographics, clinical presentation,
radiological features, treatment and follow-up are presented with
the size, location, the histological grading of the tumour and the
survival. We found a slight predominance of men (61%), and a predilection
for the distal femur (33%) and proximal humerus (33%). The metaphysis
was the most common site (47%) and the most common presentation
was with pain (44%). Half the tumours were classified histologically
as grade 1. Pulmonary metastases were reported in one patient after
an intra-lesional resection. A second patient died from local recurrence
and possible pulmonary and skin metastases after an incomplete resection. It is clearly important to make the diagnosis appropriately because
an incomplete resection may result in local recurrence and metastatic
spread. Staging for metastatic disease is recommended in grade II
or III lesions. These patients should be managed with a contrast-enhanced MRI
of the tumour and histological confirmation by biopsy, followed
by Cite this article:
Nanotechnology is the study, production and controlled
manipulation of materials with a grain size <
100 nm. At this
level, the laws of classical mechanics fall away and those of quantum
mechanics take over, resulting in unique behaviour of matter in
terms of melting point, conductivity and reactivity. Additionally,
and likely more significant, as grain size decreases, the ratio
of surface area to volume drastically increases, allowing for greater interaction
between implants and the surrounding cellular environment. This
favourable increase in surface area plays an important role in mesenchymal
cell differentiation and ultimately bone–implant interactions. Basic science and translational research have revealed important
potential applications for nanotechnology in orthopaedic surgery,
particularly with regard to improving the interaction between implants
and host bone. Nanophase materials more closely match the architecture
of native trabecular bone, thereby greatly improving the osseo-integration
of orthopaedic implants. Nanophase-coated prostheses can also reduce
bacterial adhesion more than conventionally surfaced prostheses.
Nanophase selenium has shown great promise when used for tumour
reconstructions, as has nanophase silver in the management of traumatic
wounds. Nanophase silver may significantly improve healing of peripheral
nerve injuries, and nanophase gold has powerful anti-inflammatory
effects on tendon inflammation. Considerable advances must be made in our understanding of the
potential health risks of production, implantation and wear patterns
of nanophase devices before they are approved for clinical use.
Their potential, however, is considerable, and is likely to benefit
us all in the future. Cite this article:
Resveratrol is a polyphenolic compound commonly found in the
skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated
by resveratrol and has been shown to promote longevity and boost
mitochondrial metabolism. We examined the effect of resveratrol
on normal and osteoarthritic (OA) human chondrocytes. Normal and OA chondrocytes were incubated with various concentrations
of resveratrol (1 µM, 10 µM, 25 µM and 50 µM) and cultured for 24,
48 or 72 hours or for six weeks. Cell proliferation, gene expression,
and senescence were evaluated.Background
Methods
The December 2013 Research Roundup360 looks at: Inflammation implicated in FAI; Ponseti and effective teaching; Unicompartmental knee design and tibial strain; Bisphosphonates and fracture healing; Antibiosis in cement; Zoledronic acid improves primary stability in revision?; Osteoporotic fractures revisited; and electroarthrography for monitoring of cartilage degeneration
We analysed the effects of commonly used medications
on human osteoblastic cell activity in vitro, specifically proliferation
and tissue
This multicentre prospective clinical trial aimed
to determine whether early administration of alendronate (ALN) delays
fracture healing after surgical treatment of fractures of the distal
radius. The study population comprised 80 patients (four men and
76 women) with a mean age of 70 years (52 to 86) with acute fragility
fractures of the distal radius requiring open reduction and internal
fixation with a volar locking plate and screws. Two groups of 40 patients
each were randomly allocated either to receive once weekly oral
ALN administration (35 mg) within a few days after surgery and continued
for six months, or oral ALN administration delayed until four months
after surgery. Postero-anterior and lateral radiographs of the affected
wrist were taken monthly for six months after surgery. No differences
between groups was observed with regard to gender (p = 1.0), age
(p = 0.916), fracture classification (p = 0.274) or bone mineral
density measured at the spine (p = 0.714). The radiographs were
assessed by three independent assessors. There were no significant
differences in the mean time to complete cortical bridging observed
between the ALN group (3.5 months ( Cite this article:
Peri-prosthetic osteolysis and subsequent aseptic
loosening is the most common reason for revising total hip replacements.
Wear particles originating from the prosthetic components interact
with multiple cell types in the peri-prosthetic region resulting
in an inflammatory process that ultimately leads to peri-prosthetic
bone loss. These cells include macrophages, osteoclasts, osteoblasts
and fibroblasts. The majority of research in peri-prosthetic osteolysis
has concentrated on the role played by osteoclasts and macrophages.
The purpose of this review is to assess the role of the osteoblast
in peri-prosthetic osteolysis. In peri-prosthetic osteolysis, wear particles may affect osteoblasts
and contribute to the osteolytic process by two mechanisms. First,
particles and metallic ions have been shown to inhibit the osteoblast
in terms of its ability to secrete mineralised bone matrix, by reducing
calcium deposition, alkaline phosphatase activity and its ability
to proliferate. Secondly, particles and metallic ions have been
shown to stimulate osteoblasts to produce pro inflammatory mediators Cite this article:
We investigated whether strontium-enriched calcium
phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results
in accelerated healing within the bone tunnel in reconstruction
of the anterior cruciate ligament (ACL). A total of 30 single-bundle
ACL reconstructions using tendo Achillis allograft were performed
in 15 rabbits. The graft on the tested limb was treated with Sr-CPC,
whereas that on the contralateral limb was untreated and served
as a control. At timepoints three, six, nine, 12 and 24 weeks after
surgery, three animals were killed for histological examination.
At six weeks, the graft–bone interface in the control group was
filled in with fibrovascular tissue. However, the gap in the Sr-CPC
group had already been completely filled in with new bone, and there
was evidence of the early formation of Sharpey fibres. At 24 weeks,
remodelling into a normal ACL–bone-like insertion was found in the
Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft
leads to accelerated graft healing within the bone tunnel in a rabbit
model of ACL reconstruction using Achilles tendon allograft. Cite this article:
Slipped capital femoral epiphysis (SCFE) is uncommon
in India and we routinely look for associated metabolic or endocrine
abnormalities. In this study we investigated a possible association
between vitamin D deficiency and SCFE. All children presenting with
SCFE during the study period had their 25-hydroxyvitamin D levels
measured as part of an overall metabolic, renal and endocrine status
evaluation, which included measurement of body mass index (BMI).
Vitamin D status was compared with age-, gender- and habitat-matched
controls with acute trauma or sepsis presenting to our emergency
department. A total of 15 children (12 boys and three girls) with a mean
age of 13 years ( Cite this article:
Matrix metalloproteinases (MMPs), responsible
for extracellular matrix remodelling and angiogenesis, might play
a major role in the response of the growth plate to detrimental
loads that lead to overuse injuries in young athletes. In order
to test this hypothesis, human growth plate chondrocytes were subjected
to mechanical forces equal to either physiological loads, near detrimental
or detrimental loads for two hours. In addition, these cells were
exposed to physiological loads for up to 24 hours. Changes in the
expression of MMPs -2, -3 and -13 were investigated. We found that expression of MMPs in cultured human growth plate
chondrocytes increases in a linear manner with increased duration
and intensity of loading. We also showed for the first time that
physiological loads have the same effect on growth plate chondrocytes
over a long period of time as detrimental loads applied for a short
period. These findings confirm the involvement of MMPs in overuse injuries
in children. We suggest that training programmes for immature athletes
should be reconsidered in order to avoid detrimental stresses and
over-expression of MMPs in the growth plate, and especially to avoid
physiological loads becoming detrimental. Cite this article:
Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments.
Periosteum is important for bone homoeostasis
through the release of bone morphogenetic proteins (BMPs) and their
effect on osteoprogenitor cells. Smoking has an adverse effect on
fracture healing and bone regeneration. The aim of this study was
to evaluate the effect of smoking on the expression of the BMPs
of human periosteum. Real-time polymerase chain reaction was performed
for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from
45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured
bones (21 smokers, 39 non-smokers). A hierarchical model of BMP
gene expression (BMP-2 >
BMP-6 >
BMP-4 >
BMP-7) was demonstrated
in all samples. When smokers and non-smokers were compared, a remarkable
reduction in the gene expression of BMP-2, -4 and -6 was noticed
in smokers. The comparison of fracture and non-fracture groups demonstrated
a higher gene expression of BMP-2, -4 and -7 in the non-fracture
samples. Within the subgroups (fracture and non-fracture), BMP gene
expression in smokers was either lower but without statistical significance
in the majority of BMPs, or similar to that in non-smokers with
regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In
smokers, BMP gene expression of human periosteum was reduced, demonstrating
the effect of smoking at the molecular level by reduction of mRNA
transcription of periosteal BMPs. Among the BMPs studied, BMP-2
gene expression was significantly
This study was designed to test the hypothesis
that the sensory innervation of bone might play an important role
in sensing and responding to low-intensity pulsed ultrasound and
explain its effect in promoting fracture healing. In 112 rats a
standardised mid-shaft tibial fracture was created, supported with
an intramedullary needle and divided into four groups of 28. These
either had a sciatic neurectomy or a patellar tendon resection as
control, and received the ultrasound or not as a sham treatment.
Fracture union, callus
Heterotopic ossification (HO) is perhaps the
single most significant obstacle to independence, functional mobility, and
return to duty for combat-injured veterans of Operation Enduring
Freedom and Operation Iraqi Freedom. Recent research into the cause(s)
of HO has been driven by a markedly higher prevalence seen in these
wounded warriors than encountered in previous wars or following
civilian trauma. To that end, research in both civilian and military
laboratories continues to shed light onto the complex mechanisms
behind HO formation, including systemic and wound specific factors,
cell lineage, and neurogenic inflammation. Of particular interest,
non-invasive
We performed a retrospective review of all patients
admitted to two large University Hospitals in the United Kingdom
over a 24-month period from January 2008 to January 2010 to identify
the incidence of atypical subtrochanteric and femoral shaft fractures
and their relationship to bisphosphonate treatment. Of the 3515 patients
with a fracture of the proximal femur, 156 fractures were in the
subtrochanteric region. There were 251 femoral shaft fractures.
The atypical fracture pattern was seen in 27 patients (7%) with
29 femoral shaft or subtrochanteric fractures. A total of 22 patients
with 24 atypical fractures were receiving bisphosphonate treatment at
the time of fracture. Prodromal pain was present in nine patients
(11 fractures); 11 (50%) of the patients on bisphosphonates suffered
12 spontaneous fractures, and healing of these fractures was delayed
in a number of patients. This large dual-centre review has established
the incidence of atypical femoral fractures at 7% of the study population,
81% of whom had been on bisphosphonate treatment for a mean of 4.6
years (0.04 to 12.1). This study does not advocate any change in the use of bisphosphonates
to prevent fragility fractures but attempts to raise awareness of
this possible problem so symptomatic patients will be appropriately
investigated. However, more work is required to identify the true
extent of this new and possibly increasing problem.
We examined whether enamel matrix derivative
(EMD) could improve healing of the tendon–bone interface following
reconstruction of the anterior cruciate ligament (ACL) using a hamstring
tendon in a rat model. ACL reconstruction was performed in both
knees of 30 Sprague-Dawley rats using the flexor digitorum tendon.
The effect of commercially available EMD (EMDOGAIN), a preparation
of matrix proteins from developing porcine teeth, was evaluated.
In the left knee joint the space around the tendon–bone interface
was filled with 40 µl of EMD mixed with propylene glycol alginate
(PGA). In the right knee joint PGA alone was used. The ligament
reconstructions were evaluated histologically and biomechanically
at four, eight and 12 weeks (n = 5 at each time point). At eight weeks,
EMD had induced a significant increase in collagen fibres connecting
to bone at the tendon–bone interface (p = 0.047), whereas the control
group had few fibres and the tendon–bone interface was composed
of cellular and vascular fibrous tissues. At both eight and 12 weeks,
the mean load to failure in the treated specimens was higher than
in the controls (p = 0.009). EMD improved histological tendon–bone
healing at eight weeks and biomechanical healing at both eight and
12 weeks. EMD might therefore have a human application to enhance
tendon–bone repair in ACL reconstruction.
Lengthening of the humerus is now an established
technique. We compared the complications of humeral lengthening
with those of femoral lengthening and investigated whether or not
the callus formation in the humerus proceeds at a higher rate than
that in the femur. A total of 24 humeral and 24 femoral lengthenings
were performed on 12 patients with achondroplasia. We measured the
pixel value ratio (PVR) of the lengthened area on radiographs and
each radiograph was analysed for the shape, type and density of
the callus. The quality of life (QOL) of the patients after humeral
lengthening was compared with that prior to surgery. The complication
rate per segment of humerus and femur was 0.87% and 1.37%, respectively.
In the humerus the PVR was significantly higher than that of the
femur. Lower limbs were associated with an increased incidence of
concave, lateral and central callus shapes. Humeral lengthening
had a lower complication rate than lower-limb lengthening, and QOL
increased significantly after humeral lengthening. Callus formation
in the humerus during the distraction period proceeded at a significantly
higher rate than that in the femur. These findings indicate that humeral lengthening has an important
role in the management of patients with achondroplasia.
The need for bone tissue supplementation exists in a wide range
of clinical conditions involving surgical reconstruction in limbs,
the spine and skull. The bone supplementation materials currently
used include autografts, allografts and inorganic matrix components;
but these pose potentially serious side-effects. In particular the
availability of the autografts is usually limited and their harvesting
causes surgical morbidity. Therefore for the purpose of supplementation
of autologous bone graft, we have developed a method for autologous
extracorporeal bone generation. Human osteoblast-like cells were seeded on porous granules of
tricalcium phosphate and incubated in osteogenic media while exposed
to mechanical stimulation by vibration in the infrasonic range of
frequencies. The generated tissue was examined microscopically following
haematoxylin eosin, trichrome and immunohistochemical staining.Objectives
Methods
Platelet-derived growth factor (PDGF) is known
to stimulate osteoblast or osteoprogenitor cell activity. We investigated
the effect of locally applied PDGF from poly- These results indicate that local application of PDGF from biodegradable
PDLLA-coated implants significantly accelerates fracture healing
in experimental animals. Further development may help fracture healing
in the clinical situation.
We studied the effects of hyperbaric oxygen (HBO) and zoledronic acid (ZA) on posterior lumbar fusion using a validated animal model. A total of 40 New Zealand white rabbits underwent posterior lumbar fusion at L5–6 with autogenous iliac bone grafting. They were divided randomly into four groups as follows: group 1, control; group 2, HBO (2.4 atm for two hours daily); group 3, local ZA (20 μg of ZA mixed with bone graft); and group 4, combined HBO and local ZA. All the animals were killed six weeks after surgery and the fusion segments were subjected to radiological analysis, manual palpation, biomechanical testing and histological examination. Five rabbits died within two weeks of operation. Thus, 35 rabbits (eight in group 1 and nine in groups 2, 3 and 4) completed the study. The rates of fusion in groups 3 and 4 (p = 0.015) were higher than in group 1 (p <
0.001) in terms of radiological analysis and in group 4 was higher than in group 1 with regard to manual palpation (p = 0.015). We found a statistically significant difference in the biomechanical analysis between groups 1 and 4 (p = 0.024). Histological examination also showed a statistically significant difference between groups 1 and 4 (p = 0.036). Our results suggest that local ZA combined with HBO may improve the success rate in posterior lumbar spinal fusion.
Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.
We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone. In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed bone formation in this area as the intramedullary canal was restored. In the intercortical area, LIPUS was considered to enhance bone formation throughout the period of observation. These findings indicate that LIPUS could shorten the time required for remodelling and enhance the
Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
Florid reactive periostitis is a pronounced periosteal reaction, usually affecting the hands and feet, for which there is no obvious cause. It is rare in children and in long bones. We report an unusual case of florid reactive periostitis in a ten-year-old girl that involved both bones of the forearm. The lesion resolved over a period of one year, leaving a residual exostosis. She developed a physeal bar in the distal ulna in the region of the lesion at one-year follow-up. This was thought to be a complication of the biopsy procedure and was treated by resection and proximal ulnar lengthening.
Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity. This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis.
We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment. The use of intramedullary nails prevented recurrence of deformity and refracture.
Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells. Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing. After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times. Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.
We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.
