We reviewed 59 bone graft substitutes marketed
by 17 companies currently available for implantation in the United Kingdom,
with the aim of assessing the peer-reviewed literature to facilitate
informed decision-making regarding their use in clinical practice.
After critical analysis of the literature, only 22 products (37%)
had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita),
Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question
the need for so many different products, especially with limited
published clinical evidence for their efficacy, and conclude that
there is a considerable need for further prospective randomised
trials to facilitate informed decision-making with regard to the
use of current and future bone graft substitutes in clinical practice. Cite this article:
Although the vast majority of patients that undergo
total knee replacement have satisfactory outcomes with a generally
low complication rate, occasionally a patient will be encountered
that has had multiple failed surgeries, and now reaches a crossroad
as to whether limb salvage will be acceptable or not. Cite this article:
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods
The purpose of this study was to investigate whether the femoral
head–neck contour, characterised by the alpha angle, varies with
the stage of physeal maturation using MRI evaluation of an asymptomatic
paediatric population. Paediatric volunteers with asymptomatic hips were recruited to
undergo MRI of both hips. Femoral head physes were graded from 1
(completely open) to 6 (completely fused). The femoral head–neck
contour was evaluated using the alpha angle, measured at the 3:00
(anterior) and 1:30 (anterosuperior) positions and correlated with
physeal grade, with gender sub-analysis performed.Objectives
Methods
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.
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.
Ancient Egypt was a highly developed agrarian society with a massive civil engineering capability. Trauma and skeletal disease were common and vestiges of the evidence for that survive, largely in the form of hieratic images and papyri dedicated to the practice of medicine. The earliest treatise on trauma is the
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:
We present our experience of forearm lengthening
in children with various conditions performed by a single surgeon between
1995 and 2009. A total of 19 children with a mean age of 9.8 years
(2.1 to 15.9) at the time of surgery had 22 forearm lengthenings
using either an Ilizarov/spatial and Ilizarov circular frame or
a monolateral external fixator. The patients were divided into two
groups: group A, in whom the purpose of treatment was to restore
the relationship between the radius and the ulna, and group B, in
whom the objective was to gain forearm length. The mean follow-up after
removal of the frame was 26 months (13 to 53). There were ten patients (11 forearms) in group A with a mean
radioulnar discrepancy of 2.4 cm (1.5 to 3.3) and nine patients
(11 forearms) in group B. In group A, the mean lengthening achieved
was 2.7 cm (1.0 to 5.5), with a lengthening index of 11.1 weeks/cm.
Equalisation or overcorrection of the discrepancy was achieved in
seven of 11 forearms, but lengthening was only partially successful
at preventing subluxation or dislocation of the radial head. In
group B, the mean lengthening achieved was 3.8 cm (1.9 to 6.8),
with a lengthening index of 7.25 weeks/cm. Common complications
in both groups were pin-site infection and poor regenerate formation. Forearm lengthening by distraction osteogenesis is a worthwhile
procedure in children that can improve cosmesis and function, particularly
in patients with shortening of both radius and ulna.
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.
The literature on fracture repair has been reviewed. The traditional concepts of delayed and nonunion have been examined in terms of the phased and balanced anabolic and catabolic responses in bone repair. The role of medical manipulation of these inter-related responses in the fracture healing have been considered.
We describe three cases of infantile tibia vara
resulting from an atraumatic slip of the proximal tibial epiphysis
upon the metaphysis. There appears to be an association between
this condition and severe obesity. Radiologically, the condition
is characterised by a dome-shaped metaphysis, an open growth plate
and disruption of the continuity between the lateral borders of
the epiphysis and metaphysis, with inferomedial translation of the
proximal tibial epiphysis. All patients were treated by realignment
of the proximal tibia by distraction osteogenesis with an external
circulator fixator, and it is suggested that this is the optimal
method for correction of this complex deformity. There are differences
in the radiological features and management between conventional
infantile Blount’s disease and this ‘slipped upper tibial epiphysis’
variant.
We have examined the deterioration of implant fixation after withdrawal of parathyroid hormone (PTH) in rats. First, the pull-out force for stainless-steel screws in the proximal tibia was measured at different times after withdrawal. The stimulatory effect of PTH on fixation was lost after 16 days. We then studied whether bisphosphonates could block this withdrawal effect. Mechanical and histomorphometric measurements were conducted for five weeks after implantation. Subcutaneous injections were given daily. Specimens treated with either PTH or saline during the first two weeks showed no difference in the mechanical or histological results (pull-out force 76 N
We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone. Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group. These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.
The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures.
The treatment of infected nonunions is difficult.
Antibiotic cement-coated (ACC) rods provide stability as well as delivering
antibiotics. We conducted a review of 110 infected nonunions treated
with ACC rods. Patients were divided into two groups: group A (67
patients) with an infected arthrodesis, and group B (43 patients)
with an infected nonunion in a long bone. In group A, infected arthrodesis,
the success rate after the first procedure was 38/67 (57%), 29/67
(43%) required further surgery for either control of infection or
non-union. At last follow-up, five patients required amputation,
representing a limb salvage rate of 62/67 (93%) overall. In all,
29/67 (43%) presented with a bone defect with a mean size of 6.78
cm (2 to 25). Of those with a bone defect, 13/29 (45%) required
further surgery and had a mean size of defect of 7.2 cm (3.5 to
25). The cultures were negative in 17/67 (26%) and the most common
organism cultured was methicillin-resistant Cite this article:
We report the results of 79 patients (81 hips)
who underwent impaction grafting at revision hip replacement using the
Exeter femoral stem. Their mean age was 64 years (31 to 83). According
to the Endoklinik classification, 20 hips had a type 2 bone defect,
40 had type 3, and 21 had type 4. The mean follow-up for unrevised
stems was 10.4 years (5 to 17). There were 12 re-operations due to intra- and post-operative
fractures, infection (one hip) and aseptic loosening (one hip).
All re-operations affected type 3 (6 hips) and 4 (6 hips) bone defects.
The survival rate for re-operation for any cause was 100% for type
2, 81.2% (95% confidence interval (CI) 67.1 to 95.3) for type 3,
and 70.8% (95% CI 51.1 to 90.5) for type 4 defects at 14 years.
The survival rate with further revision for aseptic loosening as
the end point was 98.6% (95% CI 95.8 to 100). The final clinical
score was higher for patients with type 2 bone defects than type
4 regarding pain, function and range of movement. Limp was most
frequent in the type 4 group (p <
0.001). The mean subsidence
of the stem was 2.3 mm ( The impacted bone grafting technique has good clinical results
in femoral revision. However, major bone defects affect clinical
outcome and also result in more operative complications.
We compared the clinical and radiographic results
of total ankle replacement (TAR) performed in non-diabetic and diabetic
patients. We identified 173 patients who underwent unilateral TAR
between 2004 and 2011 with a minimum of two years’ follow-up. There
were 88 male (50.9%) and 85 female (49.1%) patients with a mean
age of 66 years ( The mean AOS and AOFAS scores were significantly better in the
non-diabetic group (p = 0.018 and p = 0.038, respectively). In all,
nine TARs (21%) in the diabetic group had clinical failure at a
mean follow-up of five years (24 to 109), which was significantly
higher than the rate of failure of 15 (11.6%) in the non-diabetic
group (p = 0.004). The uncontrolled diabetic subgroup had a significantly
poorer outcome than the non-diabetic group (p = 0.02), and a higher
rate of delayed wound healing. The incidence of early-onset osteolysis was higher in the diabetic
group than in the non-diabetic group (p = 0.02). These results suggest
that diabetes mellitus, especially with poor glycaemic control,
negatively affects the short- to mid-term outcome after TAR. Cite this article:
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
The relationship between post-operative bone
density and subsequent failure of total knee replacement (TKR) is
not known. This retrospective study aimed to determine the relationship
between bone density and failure, both overall and according to
failure mechanism. All 54 aseptic failures occurring in 50 patients
from 7760 consecutive primary cemented TKRs between 1983 and 2004
were matched with non-failing TKRs, and 47 failures in 44 patients
involved tibial failures with the matching characteristics of age
(65.1 for failed and 69.8 for non-failed), gender (70.2% female), diagnosis
(93.6% OA), date of operation, bilaterality, pre-operative alignment
(0.4 and 0.3 respectively), and body mass index (30.2 and 30.0 respectively).
In each case, the density of bone beneath the tibial component was assessed
at each follow-up interval using standardised, calibrated radiographs.
Failing knees were compared with controls both overall and, as a
subgroup analysis, by failure mechanism. Knees were compared with
controls using univariable linear regression. Significant and continuous elevation in tibial density was found
in knees that eventually failed by medial collapse (p <
0.001)
and progressive radiolucency (p <
0.001) compared with controls,
particularly in the medial region of the tibia. Knees failing due
to ligamentous instability demonstrated an initial decline in density
(p = 0.0152) followed by a non-decreasing density over time (p =
0.034 for equivalence). Non-failing knees reported a decline in
density similar to that reported previously using dual-energy x-ray
absorptiometry (DEXA). Differences between failing and non-failing
knees were observable as early as two months following surgery.
This tool may be used to identify patients at risk of failure following
TKR, but more validation work is needed. Cite this article: