Study Design. Prospective cohort study. Objective. To assess the safety and efficacy of an intra-operative gamma probe in the surgical treatment of
Aim. This study describes the histologic changes seen with a gentamicin-eluting synthetic bone graft substitute (BGS)(1) in managing bone defects after resection of chronic osteomyelitis (cOM). Method. 154 patients with mean follow-up of 21.8 months (12–56) underwent treatment of cOM with an antibiotic-loaded BGS for defect filling. Nine patients had subsequent surgery, not related to infection recurrence, allowing biopsy of the implanted material. These biopsies were harvested between 19 days and two years after implantation, allowing a description of the material's remodelling over time. Samples were fixed in formalin and stained with haematoxylin-eosin. Immunohistochemistry, using an indirect immunoperoxidase technique, identified the osteocyte markers Dentine Matrix Protein-1 (DMP-1) and Podoplanin, the macrophage/osteoclast marker CD68, and the macrophage marker CD14. Results. The material was actively remodelled and was osteoconductive. There was evidence of osteoblast recruitment, leading to
Aim. To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum. Method. The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 10. 4. CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 10. 4. CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed. Results. The separation of aggregates into different size fractions was done successfully by the filtering method. Isothermal microcalorimetry showed, a delayed Time-to-peak metabolic activity of the aggregate-inoculum compared to the planktonic inoculum. S. aureus was isolated from subcutis, bone and implants from all animals in groups A and B. Both group A animals showed osteomyelitis at gross inspection with suppuration and sequestration, while groups B and C animals had no macroscopic lesions. From CT scans, both group A animals also showed positive signs of osteomyelitis, i.e., osteolysis, while only one animal in group B did, and none in group C. Histopathological examination of the bones showed more extensive inflammation in group A animals compared to those in group B, which showed more
Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralisation, which is vital for normal bone development, its biomechanical competence and fracture healing. Phosphatase, orphan 1 (PHOSPHO1), a bone-specific phosphatase, has been shown to be involved in the mineralisation of the extracellular matrix in bone. It can hydrolyse phosphoethanolamine and phosphocholine to generate inorganic phosphate, which is crucial for bone mineralisation. Phospho1−/− mice show hypomineralised bone and spontaneous fractures. All these data led to the hypothesis that PHOSPHO1 is essential for bone mineralisation and its structural integrity. However, no study to our knowledge has shown the effects of PHOSPHO1 on bone fracture healing. In this study, we examined how PHOSPHO1-deficiency might affect the healing and quality of the fractured bones in Phospho1−/− mice. We performed rodded immobilised fracture surgery on the right tibia of control wild type (WT) and Phospho1−/− mice (n=16 for each group) at eight weeks of age. Bone was left to heal for four weeks and then the mice were euthanised and their tibias were analysed using Faxitron X-ray analyses, microCT, histology and histomorphometry and three-point bending test. Our microCT and X-ray analyses revealed that the appearance of the callus and several static parameters of bone remodeling at the fracture sites were markedly different in WT and Phospho1−/− mice. We observed a significant increase of BS/BV, BS/TV and trabecular number and decrease in trabecular thickness and separation in Phospho1−/− callus in comparison to the WT callus. These observations were further confirmed by histomorphometry. The increased bone mass at the fracture sites of Phospho1−/− mice appears to be caused by increased bone formation as there is a significant increase of osteoblast number, while osteoclast numbers remained unchanged. There was a marked increase of
Introduction. Bony tumours of the foot account for approximately 3% of all osseous tumours. However, literature regarding os calcis and talar tumours comprises individual case reports, short case series or literature reviews with no recent large series. Methods. We retrospectively reviewed the medical notes and imaging for all patients with calcaneal or talar tumours recorded in the Scottish Bone Tumour Registry since the 1940's. Demographics, presentation, investigation, histology, management and outcome were reviewed. Results. 34 calcaneal tumours and 23 talar tumours were identified. Calcaneal tumours. 2:1 male prevalence, mean age at presentation 30, average length of symptoms 9 months. 4 cases presented with pathological fracture. 21 benign tumours including 6 unicameral bone cysts, 3 chondroblastoma, and a wide variety of individual lesions. 13 malignant tumours comprising 6 osteosarcoma, 5 chondrosarcoma and 2 Ewings sarcoma. Talar Tumours. male to female ratio 3:1, mean age at presentation 28, average length of symptoms 5 months. 20 benign cases including 7
Purpose. Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained. Method. Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology,
Aim. This study describes and correlates the radiographic and histologic changes which develop in a Gentamicin-eluting synthetic bone graft substitute. *. in the management of bone defects after resection of chronic osteomyelitis (COM). Method. 100 patients with COM were treated with a single stage procedure, including management of the dead space with insertion of a Gentamicin-eluting synthetic bone graft substitute. *. Radiographs of 73 patients with a follow-up of at least 12 months (range 12–33 months) were available for review. Bone defects were diaphyseal in 32, metaphyseal in 34 and combined in 7 patients. In 3 patients, radiographs were not of sufficient quality to allow analysis. Five patients had subsequent surgery, not related to recurrence of infection, which allowed biopsy of the implanted material. These biopsies were harvested between 12 days and 9 months after implantation. Tissue was fixed in formalin and stained with haematoxylin-eosin and immunohistochemically for bone matrix markers. Results. Radiographic: 31 of 34 diaphyseal implantations (91%) demonstrated remodelling of the biocomposite, gradually over many months, producing new bone and resulting in a “normal post-osteomyelitic” appearance. In metaphyseal implantations, new bone filled two-thirds or more of the defect in 55% of cases, one to two-thirds was filled in 31% and one third or less was filled in 14%. 22% of patients exhibited radiographic signs of dissolution and remodelling which are specific to this material. The ‘Halo’ sign of peripheral zone remodelling, the ‘Marble’ sign of dissolution and the ‘Puddle’ sign of distal migration can be described. Histologic: Histological assessment revealed early active remodelling of the biocomposite. The material was osteoconductive with accumulation of osteoblasts and
Structural bone allografts are a viable option in reconstructing massive bone defects in patients following musculoskeletal (MSK) tumour resection and revision hip/knee replacements. To decrease infection risk, bone allografts are often sterilised with gamma-irradiation, which consequently degrades the bone collagen connectivity and makes the bone brittle. Clinically, irradiated bone allografts fracture at rates twice that of fresh non-irradiated allografts. Our lab has developed a method that protects the bone collagen connectivity through ribose pre-treatment while still undergoing gamma-irradiation. Biomechanical testing of bone pretreated with our method provided 60–70% protection of toughness and 100% protection of strength otherwise lost with conventional irradiation. This study aimed to determine if the ribose-treated bone allografts are biocompatible with host bone. The New Zealand White rabbit (NZWr) radius segmental defect model was used, in which 15-mm critically-sized defects were created. Bone allografts were first harvested from the radial diaphysis of donor female NZWr, and treated to create 3 graft types: C=untreated controls, I=conventionally-irradiated (33 kGy), R=our ribose pretreated + irradiation method. Recipient female NZWr (n=24) were then evenly randomised into the 3 graft groups. Allografts were surgically fixed with a 0.8-mm Kirschner wire. Post-operative X-rays were taken at 2, 6, and 12 weeks, with bony healing assessed by a blinded MSK radiologist using an established radiographic scoring system. The reconstructed radii were retrieved at 12 weeks and analysed using bone histomorphometry and microCT. Kruskal-Wallis and Mann-Whitney tests were utilised to compare groups, with statistical significance when p<0.05. Radiographic analysis revealed no differences in periosteal reaction and degree of osteotomy site union between the groups at any time point. Less cortical remodeling was observed in R and I grafts compared to untreated controls at 6 weeks (p=0.004), but was no longer evident by 12 weeks. Radiographic union was achieved in all groups by 12 weeks. Histologic and microCT analysis further confirmed union at the graft-host bone interface, with the presence of mineralising callus and
Introduction. The femoral neck in children is a common site for bone lesions. The majority are benign. However these lesions can cause diagnostic problems. Aim. To present a spectrum of chronic lesions of the femoral neck in children and emphasize the importance of tissue diagnosis. Materials and methods. Thirty two children with isolated chronic bone lesions in the femoral neck treated between 1994 and 2013were retrospectively reviewed. The ages ranged between 1–13 years. Clinical features were pain and limp. Routine blood tests, x-rays and CT scans were done in all and MRI scans in 5 cases. All diagnoses were confirmed histologically. Results. Three radiological patterns were seen: lucent or cystic in 22, infiltrative (permeative)in 2, and localized densities with nidus in 8 cases. Histologically the lesions were subacute osteomyelitis in 4, tuberculosis in 9, simple bone cyst in 7,
Purpose of the study. To review the primary bone tumours of the spine treated at our unit. Description of methods. Retrospective review of folders and x-rays of all the patients with primary bone tumours of the spine treated at our unit between 2005 and 2012. All haematological tumours were excluded. Summary of results. We treated 15 cases during this period. The median age at presentation was 36 years (8–65). There was a significant delay from onset of symptoms to diagnosis in most cases (median 7 months). Histological diagnoses included:. -Benign tumours. Active. Hemangioma. 3.
Introduction:. 20 cases of bone defect have been treated by the induced membrane technique avoiding allograft, microsurgery and amputation. Material and Methods:. 9 cases of long bone defect (humerus and forearm) and 11 cases of bone defect at the hand have been included in this multicentre prospective study (3 centers). The aetiology in 11 cases was trauma, 7 cases were septic nonunions and 2 cases followed tumors. In the hand the bone loss was at least one phalanx, and for long bones the mean defect was 5 cm (3–11). All cases were treated by the induced membrane technique which consists in stable fixation, flap if necessary and in filling the void created by the bone defect by a cement spacer (PMMA). This technique needs a second stage procedure at the 2. nd. month where the cement is removed and the void is filled by cancellous bone. The key point of this induced membrane technique is to respect the foreign body membrane which appeared around the cement spacer and which creates a biologic chamber for the second procedure. Bone union was evaluated prospectively in each case by a surgeon not involved in the treatment, by X-ray and CT scan. Failure was defined as a nonunion at 1 year, or an uncontrolled sepsis at 1 month. Results:. 3 cases failed to achieve bone union, 2 in the hand and 1 in a long bone. No septic complications occurred and all septic cases healed. In 14 cases bone union was achieved with a delay of 5 months (1, 5–12). 2 biopsies allowed us to prove that
Aim. This study aims to determine the value of MRI in children with hip pain which remained unexplained following routine investigations including ultrasound examination. Materials and methods. Retrospective review of clinical notes and MRI findings in all children who received and MRI scan for undiagnosed hip pain over three years. Results. Fifty five children underwent an MRI scan of their hips for unexplained hip pain. 29 were male and 26 were female. The mean age was 10.9 years. The MR study provided a diagnosis in 22 children (40%), and was normal in 33 children (60%). Five cases were considered to be due to transient synovitis. Three children were diagnosed as
Introduction. Titanium (Ti) alloys are used as porous bone ingrowth materials on non-cemented knee arthroplasty tibial tray implants. Nano-surface mechanism that increase the osseointegration rate between Ti alloys, and surrounding tissue has been recognized to improve the interface to ultimately allow patients to weight bear on non-cemented arthroplasty implants sooner. Bioactive TiO. 2. nanotube arrays has been shown to accelerate osseointegration. Ideally, these surfaces would both increase the adhesion of bone to the implant and help to reduction of infection to substitute for antibiotic bone cement. This study examines a combination treatment of both TiO. 2. nanotubes combined with silver nano-deposition, that simultaneously enhances osseointegration while improving infection resistance, by testing ex vivo implantation stability in an equine cadaver bone followed by in vitro and in vivo analysis to understand the biocompatibility and early stage osseointegration. Methods. 100nm diameter and 300nm length TiO. 2. nanotubes were formed on a CP titanium surface using anodization method at 20V for 45mins using 1% HF electrolyte. Silver deposition on TiO. 2. nanotubes were performed using 0.1M AgNO. 3. solution at 3V for 45s. Figure 1 shows SEM images showing (a) TiO. 2. nanotubes of 300nm length and (b) nanotubes with silver coating). Ti anodized samples with and without silver nanotubes implanted into an equine cadaver bone in an ex vivo manner to study the stability of nanotubes and the adherence of silver deposition. Silver release study was performed for a period of 14 days in a similar ex vivo manner. Dimensions for implantation samples: 2.5 mm diam. × 15 mm. For cell culture, circular disc samples 12.5mm in diameter and 3 mm in thickness were used to study the bone cell-material interactions using human fetal osteoblast (hFOB) cells. To evaluate the cell proliferation, MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay was used. The in vitro cell-materials interaction study was performed for a period of 4 and 7 days. In vivo study was performed using rat distal femur model for a period of 12 weeks with dense Ti samples as control (Sample dimensions: 3mm diam. × 5mm). At the end of 12 weeks, the samples were analyzed for early stage osseointegration using histological analysis and SEM imaging. Results. No significant changes in the morphology of nanotubes was observed due to the implantation process which signifies the damage resistance these nanotubes can endure during implantation and explantation. Figure 2 shows SEM images of (a) & (b) nanotubes without silver coating before and after implantation and (c) & (d) nanotubes with silver coating before and after implantation respectively. Silver nanocoatings can be observed after implantation which shows the adherence of the antimicrobial nano-coating on the surface of nanotubes. Cumulative release profiles of silver ions after 14 days showed the total release was in the effective range for antimicrobial characteristics and was well below the toxic limit specified for human cells (10 ppm) Figure 3(a) shows cumulative release profile of silver after 14 days. MTT assay and SEM images show good cell proliferation, antimicrobial effect, and increase in cell density after 7 days for samples with nanotubes and silver with no cytotoxic effects and good cell attachment on the samples as shown in Figure 3(b) MTT assay results showing cell densities after 4 and 7 days and Figure 3(c) SEM images showing cell attachment after 4 and 7 days on samples. Histological analysis and SEM images showed
Purpose. The hip region is the second most common site for tuberculosis following the spine in children. The aim is to describe the variable radiological patterns of presentation and their resemblance to pyogenic infection, tumours and other benign conditions of bone in children. Methods. The clinical and radiological records of 29 children aged 10 months–13 years with confirmed tuberculosis of the hip region seen between 1990 and 2011 were reviewed retrospectively. Clinical features were pain, limp and flexion, adduction contractures. Abscesses and sinuses were seen in 4 children. The ESR ranged between 7–110 mm/hr. Mantoux was positive in 20 children. All cases were histologically confirmed. Treatment involved biopsy, currettage of bone defects, limited synovectomy and adductor tenotomy. Patients were immobilised for 4 weeks on a spica cast or traction. Antituberculous treatment was administered for 9–12 months. Results. Radiologically 9 lesions were extra-articular and 20 involved the joint synovium and articular surface. Extra-articular lesions were seen in the pubis, greater and lesser trochanter, ilium, proximal femur and peri-acetabular regions. Intra-articular lesions were seen in the femoral head, neck and acetabulum. Dislocations and subluxations occurred in 8 patients; various lesions mimicked pyogenic arthritis, idiopathic chondrolysis, chondrobastoma, Perthes disease, eosinophilic granuloma and
Osteocytes (OCY) are the end stage differentiation cells of the osteoblast lineage, and are incorporated in the bone matrix during bone formation. In doing so, OCY control the mineralisation of
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:
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: