Platelet-derived growth factor (PDGF) is known to stimulate osteoblast or osteoprogenitor cell activity. We investigated the effect of locally applied PDGF from poly-d,l-lactide (PDLLA)-coated implants on fracture healing in a rat model. A closed fracture of the right tibia of four-month-old Sprague-Dawley rats (n = 40) was stabilised with implants coated with a biodegradable PDLLA versus implants coated with PDLLA and PDGF. Radiographs were taken throughout the study, and a marker of DNA activity, bromodeoxyuridine (BrdU), was injected before the rats were killed at three, seven and ten days. The radiographs showed consolidation of the callus in the PDGF-treated group compared with the control group at all three time points. In the PDGF-treated group, immunohistochemical staining of BrdU showed that the distribution of proliferating cells in all cellular events was higher after ten days compared with that at three and seven days.

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.

Blast and ballistic weapons used on the battlefield cause devastating injuries rarely seen outside armed conflict. These extremely high-energy injuries predominantly affect the limbs and are usually heavily contaminated with soil, foliage, clothing and even tissue from other casualties. Once life-threatening haemorrhage has been addressed, the military surgeon’s priority is to control infection.

Combining historical knowledge from previous conflicts with more recent experience has resulted in a systematic approach to these injuries. Urgent debridement of necrotic and severely contaminated tissue, irrigation and local and systemic antibiotics are the basis of management. These principles have resulted in successful healing of previously unsurvivable wounds. Healthy tissue must be retained for future reconstruction, vulnerable but viable tissue protected to allow survival and avascular tissue removed with all contamination.

While recent technological and scientific advances have offered some advantages, they must be judged in the context of a hard-won historical knowledge of these wounds. This approach is applicable to comparable civilian injury patterns. One of the few potential benefits of war is the associated improvement in our understanding of treating the severely injured; for this positive effect to be realised these experiences must be shared.

The outcome after total hip replacement has improved with the development of surgical techniques, better pain management and the introduction of enhanced recovery pathways. These pathways require a multidisciplinary team to manage pre-operative education, multimodal pain control and accelerated rehabilitation. The current economic climate and restricted budgets favour brief hospitalisation while minimising costs. This has put considerable pressure on hospitals to combine excellent results, early functional recovery and shorter admissions.

In this review we present an evidence-based summary of some common interventions and methods, including pre-operative patient education, pre-emptive analgesia, local infiltration analgesia, pre-operative nutrition, the use of pulsed electromagnetic fields, peri-operative rehabilitation, wound dressings, different surgical techniques, minimally invasive surgery and fast-track joint replacement units.

Cite this article: Bone Joint J 2013;95-B:1587–94.

Metal-on-metal total hip replacement has been targeted at younger patients with anticipated long-term survival, but the effect of the production of metal ions is a concern because of their possible toxicity to cells. We have reviewed the results of the use of the Ultima hybrid metal-on-metal total hip replacement, with a cemented polished tapered femoral component with a 28 mm diameter and a cobalt-chrome (CoCr) modular head, articulating with a 28 mm CoCr acetabular bearing surface secured in a titanium alloy uncemented shell.

Between 1997 and 2004, 545 patients with 652 affected hips underwent replacement using this system. Up to 31 January 2008, 90 (13.8%) hips in 82 patients had been revised. Pain was the sole reason for revision in 44 hips (48.9%) of which 35 had normal plain radiographs. Peri-prosthetic fractures occurred in 17 hips (18.9%) with early dislocation in three (3.3%) and late dislocation in 16 (17.8%). Infection was found in nine hips (10.0%).

At operation, a range of changes was noted including cavities containing cloudy fluid under pressure, necrotic soft tissues with avulsed tendons and denuded osteonecrotic upper femora. Corrosion was frequently observed on the retrieved cemented part of the femoral component. Typically, the peri-operative findings confirmed those found on pre-operative metal artefact reduction sequence MRI and histological examination showed severe necrosis.

Metal artefact reduction sequence MRI proved to be useful when investigating these patients with pain in the absence of adverse plain radiological features.

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically.

Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.

Limited forefoot amputation in diabetic patients with osteomyelitis is frequently required. We retrospectively reviewed diabetic patients with osteomyelitis, an unhealed ulcer and blood pressure in the toe of > 45 mmHg who underwent limited amputation of the foot with primary wound closure. Between 2006 and 2012, 74 consecutive patients with a mean age of 67 years (29 to 93), and a median follow-up of 31 months, were included. All the wounds healed primarily at a median of 37 days (13 to 210; mean 48). At a median of 6 months (1.5 to 18; mean 353 days), 23 patients (31%) suffered a further ulceration. Of these, 12 patients (16% of the total) required a further amputation.

We conclude that primary wound closure following limited amputation of the foot in patients with diabetes is a safe and effective technique when associated with appropriate antibiotic treatment.

Cite this article: Bone Joint J 2013;95-B:1083–7.

Complications involving the patellofemoral joint, caused by malrotation of the femoral component during total knee replacement, are an important cause of persistent pain and failure leading to revision surgery. The aim of this study was to determine and quantify the influence of femoral component malrotation on patellofemoral wear, and to determine whether or not there is a difference in the rate of wear of the patellar component when articulated against oxidised zirconium (OxZr) and cobalt-chrome (CoCr) components. An in vitro method was used to simulate patellar maltracking for both materials. Both rates of wear and changes in height on the patellar articular surface were measured. The mean rates of wear measured were very small compared to standard tibiofemoral wear rates. When data for each femoral component material were pooled, the mean rate of wear was 0.19 mm³/Mcycle (sd 0.21) for OxZr and 0.34 mm³/Mcycle (sd 0.335) for CoCr. The largest change in height on each patella varied from -0.05 mm to -0.33 mm over the different configurations.

The results suggest that patellar maltracking due to an internally rotated femoral component leads to an increased mean patellar wear. Although not statistically significant, the mean wear production may be lower for OxZr than for CoCr components.

We hypothesised that cells obtained via a Reamer–Irrigator–Aspirator (RIA) system retain substantial osteogenic potential and are at least equivalent to graft harvested from the iliac crest. Graft was harvested using the RIA in 25 patients (mean age 37.6 years (18 to 68)) and from the iliac crest in 21 patients (mean age 44.6 years (24 to 78)), after which ≥ 1 g of bony particulate graft material was processed from each. Initial cell viability was assessed using Trypan blue exclusion, and initial fluorescence-activated cell sorting (FACS) analysis for cell lineage was performed. After culturing the cells, repeat FACS analysis for cell lineage was performed and enzyme-linked immunosorbent assay (ELISA) for osteocalcin, and Alizarin red staining to determine osteogenic potential. Cells obtained via RIA or from the iliac crest were viable and matured into mesenchymal stem cells, as shown by staining for the specific mesenchymal antigens CD90 and CD105. For samples from both RIA and the iliac crest there was a statistically significant increase in bone production (both p < 0.001), as demonstrated by osteocalcin production after induction.

Medullary autograft cells harvested using RIA are viable and osteogenic. Cell viability and osteogenic potential were similar between bone grafts obtained from both the RIA system and the iliac crest.

Cite this article: Bone Joint J 2013;95-B:1269–74.

Although it has been suggested that the outcome after revision of a unicondylar knee replacement (UKR) to total knee replacement (TKR) is better when the mechanism of failure is understood, a comparative study on this subject has not been undertaken.

A total of 30 patients (30 knees) who underwent revision of their unsatisfactory UKR to TKR were included in the study: 15 patients with unexplained pain comprised group A and 15 patients with a defined cause for pain formed group B. The Oxford knee score (OKS), visual analogue scale for pain (VAS) and patient satisfaction were assessed before revision and at one year after revision, and compared between the groups.

The mean OKS improved from 19 (10 to 30) to 25 (11 to 41) in group A and from 23 (11 to 45) to 38 (20 to 48) in group B. The mean VAS improved from 7.7 (5 to 10) to 5.4 (1 to 8) in group A and from 7.4 (2 to 9) to 1.7 (0 to 8) in group B. There was a statistically significant difference between the mean improvements in each group for both OKS (p = 0.022) and VAS (p = 0.002). Subgroup analysis in group A, performed in order to define a patient factor that predicts outcome of revision surgery in patients with unexplained pain, showed no pre-operative differences between both subgroups.

These results may be used to inform patients about what to expect from revision surgery, highlighting that revision of UKR to TKR for unexplained pain generally results in a less favourable outcome than revision for a known cause of pain.

Cite this article: Bone Joint J 2013;95-B:1204–8.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

The aims of this study were to evaluate the incidence of local argyria in patients with silver-coated megaprostheses and to identify a possible association between argyria and elevated levels of silver both locally and in the blood. Between 2004 and 2011, 32 megaprostheses with silver coatings were implanted in 20 female and 12 male patients following revision arthroplasty for infection or resection of a malignant tumour, and the levels of silver locally in drains and seromas and in the blood were determined. The mean age of the patients was 46 years (10 to 81); one patient died in the immediate post-operative period and was excluded.

Seven patients (23%) developed local argyria after a median of 25.7 months (interquartile range 2 to 44.5). Patients with and without local argyria had comparable levels of silver in the blood and aspiration fluids. The length of the implant did not influence the development of local argyria. Patients with clinical evidence of local argyria had no neurological symptoms and no evidence of renal or hepatic failure. Thus, we conclude that the short-term surveillance of blood silver levels in these patients is not required.

Cite this article: Bone Joint J 2013;95-B:988–92.

When using a staged approach to eradicate chronic infection after total hip replacement, systemic delivery of antibiotics after the first stage is often employed for an extended period of typically six weeks together with the use of an in situ antibiotic-eluting polymethylmethacrylate interval spacer. We report our multi-surgeon experience of 43 consecutive patients (44 hips) who received systemic vancomycin for two weeks in combination with a vancomycin- and gentamicin-eluting spacer system in the course of a two-stage revision procedure for deep infection with a median follow-up of 49 months (25 to 83).

The antibiotic-eluting articulating spacers fractured in six hips (13.9%) and dislocated in five patients (11.6%). Successful elimination of the infecting organisms occurred in 38 (92.7%) of 41 hips with three patients developing superinfection with a new organism.

We conclude that prolonged systemic antibiotic therapy may not be essential in the two-stage treatment of a total hip replacement for Gram-positive infection, provided that a high concentration of antibiotics is delivered locally using an antibiotic-eluting system.

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture.

The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone.

Objectives

The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT).

The aim of this study was to evaluate whether coating titanium discs with selenium in the form of sodium selenite decreased bacterial adhesion of Staphylococcus aureus and Staph. epidermidis and impeded osteoblastic cell growth.

In order to evaluate bacterial adhesion, sterile titanium discs were coated with increasing concentrations of selenium and incubated with bacterial solutions of Staph. aureus (ATCC 29213) and Staph. epidermidis (DSM 3269) and stained with Safranin-O. The effect of selenium on osteoblastic cell growth was also observed. The adherence of MG-63 cells on the coated discs was detected by staining with Safranin-O. The proportion of covered area was calculated with imaging software.

The tested Staph. aureus strain showed a significantly reduced attachment on titanium discs with 0.5% (p = 0.011) and 0.2% (p = 0.02) selenium coating. Our test strain from Staph. epidermidis showed a highly significant reduction in bacterial adherence on discs coated with 0.5% (p = 0.0099) and 0.2% (p = 0.002) selenium solution. There was no inhibitory effect of the selenium coating on the osteoblastic cell growth.

Selenium coating is a promising method to reduce bacterial attachment on prosthetic material.

Cite this article: Bone Joint J 2013;95-B:678–82.

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age.

Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age.

Systemic capillary leak syndrome, or the Clarkson syndrome, is an extremely rare condition in which increased capillary permeability results in a massive shift of fluid into the extravascular space. This is followed rapidly by hypotensive shock, haemoconcentration, and, potentially, substantial oedema of the limbs resulting in an acute compartment syndrome. It is important for orthopaedic surgeons to be aware of this syndrome as our medical colleagues, who initially care for these patients, are less familiar with the diagnosis and the need for emergency management of the associated compartment syndrome should it develop. There have been fewer than 100 cases of this entity reported.

This case report is the first to describe the subsequent development of a compartment syndrome in all four limbs. Clinical vigilance and continuous monitoring of intracompartmental pressure is necessary in these patients in order to help reduce limb-threatening complications.

Successful healing of a nine-year tibial nonunion resistant to six previous surgical procedures was achieved by tissue engineering. We used autologous bone marrow stromal cells (BMSCs) expanded to 5 × 10⁶ cells after three weeks’ tissue culture. Calcium sulphate (CaSO₄) in pellet form was combined with these cells at operation. The nonunion was clinically and radiologically healed two months after implantation.

This is the description of on healing of a long-standing tibial nonunion by tissue engineering. The successful combination of BMSCs and CaSO₄ has not to our knowledge been reported in a clinical setting.

The scoliosis observed in chickens after pinealectomy resembles that seen in humans with an adolescent idiopathic scoliosis, suggesting that melatonin deficiency may be responsible. However, to date there have been no studies of pineal gland glucose metabolism in patients with adolescent idiopathic scoliosis that might support this hypothesis.

We examined the excretion of urinary 6-sulfatoxyl-melatonin as well as the glucose metabolism of the pineal gland in 14 patients with an adolescent idiopathic scoliosis and compared them with those of 13 gender-matched healthy controls using F-18 fluorodeoxyglucose brain positron emission tomography. There was no significant difference in the level of urinary 6-sulfatoxyl-melatonin or pineal gland metabolism between the study and the control group. We conclude that permanent melatonin deficiency is not a causative factor in the aetiology of adolescent idiopathic scoliosis.

The purpose of this study was twofold: first, to determine whether the five-year results of hip resurfacing arthroplasty (HRA) in Canada justified the continued use of HRA; and second, to identify whether greater refinement of patient selection was warranted.

This was a retrospective cohort study that involved a review of 2773 HRAs performed between January 2001 and December 2008 at 11 Canadian centres. Cox’s proportional hazards models were used to analyse the predictors of failure of HRA. Kaplan–Meier survival analysis was performed to predict the cumulative survival rate at five years. The factors analysed included age, gender, body mass index, pre-operative hip pathology, surgeon’s experience, surgical approach, implant sizes and implant types. The most common modes of failure were also analysed.

The 2773 HRAs were undertaken in 2450 patients: 2127 in men and 646 in women. The mean age at operation was 50.5 years (sd 8.72; 18 to 82) and mean follow-up was 3.4 years (sd 2.1; 2.0 to 10.1). At the last follow-up a total of 101 HRAs (3.6%) required revision. Using revision for all causes of failure as the endpoint, Kaplan–Meier survival analysis showed a cumulative survival of 96.4% (95% confidence interval (CI) 96.1 to 96.9) at five years. With regard to gender, the five-year overall survival was 97.4% in men (95% CI 97.1 to 97.7) and 93.6% in women (95% CI 92.6 to 94.6). Female gender, smaller femoral components, specific implant types and a diagnosis of childhood hip problems were associated with higher rates of failure. The most common cause of failure was fracture of the femoral neck, followed by loosening of the femoral component.

The failure rates of HRA at five years justify the ongoing use of this technique in men. Female gender is an independent predictor of failure, and a higher failure rate at five years in women leads the authors to recommend this technique only in exceptional circumstances for women.

Cite this article: Bone Joint J 2013;95-B:1044–50.