Statement of purpose. To determine the outcome of the use of
Cahill et. al. published a large review of the use of BMP in spinal fusions. They reviewed the nationwide inpatient database, which represents approximately 25% of use U.S. Community Hospitals from the years 2002 to 2006. This included over 300,000 fusion type procedures. They noted increased complications with the use of anterior cervical procedures specifically increased complications with increased dysphasia and wound complications. Due to these concerns, the Food and Drug Administration released last year a public health notification about the potential life threatening complications related to the use of BMP in anterior cervical spine fusions. Joseph & Rampersaud noticed a 20% incidence of heterotopic ossification in patients undergoing this procedure versus only 8% for patients who had undergone fusions without BMP. Wong et. al. published a report on five cases of neurologic injury that relate to the use of BMP and the formation of heterotopic bone. Again, the suggestion of a barrier or closure defect was brought up and this may help minimise the risks; however, further work is noted. Multiple authors have noted a phenomenon of osteolysis occurring around graft fusion sites for the use of BMP. McCullen et. al. evaluated that 32 levels in 26 patients who had undergone a TLIF procedure. It is unclear the carcinogenic and tetraogenic effects of the use of BMP in the spine and also, the effects of repeat exposures on BMP has yet to be addressed. Finally, the long term cost and benefits of the use of BMP on the health care system has yet to be fully addressed. So in conclusion, BMP2 is effective in producing fusions especially in challenging environments, deformity, smoking and infection. However, the complications continue to be a concern especially with regards to interbody fusions as well as in the cervical spine.
The purpose of this study was to evaluate the efficacy of human recombinant osteogenic protein 1 (rhBMP-7) for the treatment of fracture non-unions and to estimate the health economics aspect of its administration. Twenty-four patients (18 males, mean age 39.1 (range 18-79)) with 25 fracture non-unions were treated with rhBMP-7 in our institution (mean follow-up 15.4 months (range 6-29)). Successful completion of treatment was defined as the achievement of both clinical and radiological union. The cost of each treatment episode was estimated including hospital stay, theatre time, orthopaedic implants, drug administration, investigations, clinic attendances, and physiotherapy treatments. The total cost of all episodes up to the point of receiving BMP-7 and similarly following treatment with BMP-7 were estimated and analysed. Of the 25 cases, 21 were atrophic (3 associated with bone loss) and 4 were infected non-unions. The mean number of operations performed prior to rhBMP-7 application was 3.4, including autologous bone graft in 9 cases and bone marrow injection in one case. In 21 out of the 25 cases (84%), both clinical and radiological union occurred. Mean hospital stay before and after receiving rhBMP-7 was 26.84 days per fracture and 7.8 days per fracture respectively. Total cost of treatments prior to BMP-7 was £346,117 [£13,844.68 per fracture]. Costs incurred following BMP-7 administration were estimated as £183,460 [£7,338.4 per fracture]. rhBMP-7 was used as a bone stimulating agent with or without conventional bone grafting with a success rate of 84% in this series of patients with persistent fracture non-unions. The average cost of its application was £7,338 [53.0% of the total costs of previous unsuccessful treatment of non –unions, p<0.05). Treating non-union is costly, but the financial burden could be reduced by early rhBMP-7 administration when a complicated or persistent non-union is present or anticipated. Therefore, this study supports the view that rhBMP-7 is a safe and power adjunct to be considered in the surgeon's armamentarium for the management of such difficult cases.
Periosteum is important for bone homoeostasis
through the release of
Osteoarthritis (OA) is a chronic degenerative joint disorder that affects millions of people. There are currently no therapies that reverse or repair cartilage degradation in OA patients. Link N (DHLSDNYTLDHDRAIH) is a naturally occurring peptide that has been shown to increase both collagen and proteoglycan synthesis in chondrocytes and intervertebral disc cells [1,2]. Recent evidence indicates that Link N activates Smad1/5 signaling in cultured rabbit IVD cells presumably by interacting with the
Bone is capable of regeneration, and defects often heal spontaneously. However, cartilage, tendon, and ligament injuries usually result in replacement if the site by organized scar tissue, which is inferior to the native tissue. The osteogenic potential of mesenchymal stem cells (MSCs) has already been verified. MSCs hold great potential for the development of new treatment strategies for a host of orthopedic conditions. The multi-lineage potential and plasticity of MSCs allow them to be building blocks for a host of nonhematopoietic tissues, including bone. More recently, several groups have reported on the successful clinical application of tissue engineering strategies in the repair of bony defects in patients secondary to trauma and tumor resection. Advances in fabrication of biodegradable scaffolds that serve as beds for MSC implantation will hopefully lead to better biocompatibility and host tissue integration. Current strategies for bone tissue engineering include the use of osteoconductive matrix devices that promote bony ingrowth, and the delivery of osteoinductive growth factors, including
Introduction. Humeral non-union may present a challenging problem. The instability from the un-united fracture leads to pain, disability and significant morbidity. The incidence of humeral shaft non-union as a complication of both operative and non-operative treatment is approximately 8% to 12%. This retrospective study reviews the results of surgical treatment of humeral fracture non-union performed by a single surgeon with a consistent surgical protocol. Material and Method. We present a retrospective analysis of a series of 51 consecutive cases of humeral fracture non-union treated in our limb reconstruction centre. Data were collected on mechanism of injury, associated co-morbidities, smoking, use of NSAIDs and treatment before referral. Patients were followed up to clinical and radiological union. Results. From 1994-2008, 48 patients with established humeral non-union were referred to our unit following initial management locally. Three patients were managed in our unit from the outset. There were 20 male and 28 female patients with a mean age of 53 years (range 15-86 years). There were 34 (68%) diaphyseal, nine (17%) proximal and eight (15%) distal humeral non-unions. The treatment in our unit involved plate fixation in 44 (86%) cases, intramedullary nailing in three (6%) and external fixation in three (6%) patients. Iliac crest bone graft,
Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Genetic diseases, traumatic injuries, or severe burns can induce this pathological condition and can lead to severe immobility. While the mechanisms by which the bony lesions arise are not completely understood, intense inflammation associated with musculoskeletal injury and/or highly invasive orthopaedic surgery is thought to induce HO. The incidence of HO has been reported between 3% and 90% following total hip arthroplasty. While the vast majority of these cases are asymptomatic, some patients will present decreased range of motion and painful swelling around the affected joints leading to severe immobility. In severe cases, ectopic bone formation may be involved in implant failure, leading to costly and painful revision surgery. The effects of surgical-related intraoperative risk factors for the formation of HO can also play a role. Prophylactic radiation therapy, and anti-inflammatory and biphosphonates agents have shown some promise in preventing HO, but their effects are mild to moderate at best and can be complicated with adverse effects. Irradiation around surgery could decrease the incidence of HO. However, high costs and the risk of soft tissue sarcoma inhibit the use of irradiation. Increased trials have demonstrated that nonsteroidal anti-inflammatory drugs (NSAID) are effective for the prevention of HO. However, the risk of gastrointestinal side effects caused by NSAID has drawn the attention of surgeons. The effect of the selective COX-2 inhibitor, celecoxib, is associated with a significant reduction in the incidence of HO in patients undergoing THA.
Introduction. We describe a minimally invasive technique that permits intra-focal bone graft of non-union sites with minimal disturbance of soft tissues and vascularity, and present the results of this technique. Materials and Methods. 10 patients with established tibia fracture non-union were judged suitable for the technique, and were treated in our limb reconstruction unit between January 1995 to June 2007. Eight patients were male, 2 were females with a mean age of 37.4 years (27–64). Five fractures were in the distal tibia and five were diaphyseal fractures. Five fractures were as a result of high velocity and 6 fractures were open. Average number of previous operations were 3 (range 1–7). Time lapse between injury to trephine grafting procedure was mean of 34 (6–168 months). 5 patients had a sedentary job, 2 were labourers and 2 were not working. There were 5 smokers and 2 obese patients. Six cases were of infected non-unions. Operative technique. Under general anaesthesia, the graft(s) was first obtained from the iliac crest using a guide wire centred trephine. A stab incision was made at the non-union site under image control. A core was taken across the non-union, taking care to breach both bone fragments. A trephine core was rolled in
Purpose. The data regarding the effects of noggin on
Numerous investigators have described osteogenic differentiation of bone marrow stromal cells obtained from both murine and human sources over the past decade. The ease of access and large available quantity of adipose tissue, however, makes Adipose-Derived Stem Cells (ADSC) a far more practical alternative for clinical applications, such as operative treatment of non-unions and regeneration of critical bone defects. Therefore, the primary goal of this research endeavor is to achieve osteogenic differentiation of ADSC. Previous work has already demonstrated that
Smoking is associated with post-operative complications but smokers
often under-report the amount they smoke. Our objective was to determine
whether a urine dipstick test could be used as a substitute for
quantitative cotinine assays to determine smoking status in patients. Between September 2013 and July 2014 we conducted a prospective
cohort study in which 127 consecutive patients undergoing a planned
foot and ankle arthrodesis or osteotomy were included. Patients
self-reported their smoking status and were classified as: ‘never
smoked’ (61 patients), ‘ex-smoker’ (46 patients), or ‘current smoker’ (20
patients). Urine samples were analysed with cotinine assays and
cotinine dipstick tests.Aims
Patients and 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:
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:
Construction of a functional skeleton is accomplished
through co-ordination of the developmental processes of chondrogenesis,
osteogenesis, and synovial joint formation. Infants whose movement Cite this article:
The ability of mesenchymal stem cells (MSCs)
to differentiate Despite their increasing application in clinical trials, the
origin and role of MSCs in the development, repair and regeneration
of organs have remained unclear. Until recently, MSCs could only
be isolated in a process that requires culture in a laboratory;
these cells were being used for tissue engineering without understanding
their native location and function. MSCs isolated in this indirect
way have been used in clinical trials and remain the reference standard
cellular substrate for musculoskeletal engineering. The therapeutic
use of autologous MSCs is currently limited by the need for In this annotation we provide an update on the recent developments
in the understanding of the identity of MSCs within tissues and
outline how this may affect their use in orthopaedic surgery in
the future. Cite this article:
Tendinopathy is a debilitating musculoskeletal
condition which can cause significant pain and lead to complete rupture
of the tendon, which often requires surgical repair. Due in part
to the large spectrum of tendon pathologies, these disorders continue
to be a clinical challenge. Animal models are often used in this
field of research as they offer an attractive framework to examine
the cascade of processes that occur throughout both tendon pathology and
repair. This review discusses the structural, mechanical, and biological
changes that occur throughout tendon pathology in animal models,
as well as strategies for the improvement of tendon healing. Cite this article:
The most frequent cause of failure after total
hip replacement in all reported arthroplasty registries is peri-prosthetic
osteolysis. Osteolysis is an active biological process initiated
in response to wear debris. The eventual response to this process
is the activation of macrophages and loss of bone. Activation of macrophages initiates a complex biological cascade
resulting in the final common pathway of an increase in osteolytic
activity. The biological initiators, mechanisms for and regulation
of this process are beginning to be understood. This article explores current
concepts in the causes of, and underlying biological mechanism resulting
in peri-prosthetic osteolysis, reviewing the current basic science
and clinical literature surrounding the topic.