The October 2015 Research Roundup360 looks at: Wasted implants; Biofilms revisited; Peri-operative anticoagulation not required in atrial fibrillation; Determinants in outcome following orthopaedic surgery; Patient ‘activation’ and outcomes; Neuroplasticity and nerve repair; KOOS Score in predicting injury?

The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs.

We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice.

Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib.

Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage.

Take home message: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease.

Cite this article: Bone Joint J 2016;98-B:160–5.

Aims

Tissue responses to debris formed by abrasion of polymethylmethacrylate (PMMA) spacers at two-stage revision arthroplasty for prosthetic joint infection are not well described. We hypothesised that PMMA debris induces immunomodulation in periprosthetic tissues.

Aims

The purpose of this study was to compare the long-term results of primary total hip arthroplasty (THA) in young patients using either a conventional (CPE) or a highly cross-linked (HXLPE) polyethylene liner in terms of functional outcome, incidence of osteolysis, radiological wear and rate of revision.

Objectives

Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results.

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.

The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.

The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.

This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.

Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Cite this article: Bone Joint J 2016;98-B:6–13.

Objectives

Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats.

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay.

The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group.

This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder.

Cite this article: Bone Joint J 2015;97-B:824–9.

Objectives

Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?

Objectives

Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the ‘race for the surface’ theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied.

Aims

The most effective surgical approach for total hip arthroplasty (THA) remains controversial. The direct anterior approach may be associated with a reduced risk of dislocation, faster recovery, reduced pain and fewer surgical complications. This systematic review aims to evaluate the current evidence for the use of this approach in THA.

Exsanguination is the second most common cause of death in patients who suffer severe trauma. The management of haemodynamically unstable high-energy pelvic injuries remains controversial, as there are no universally accepted guidelines to direct surgeons on the ideal use of pelvic packing or early angio-embolisation. Additionally, the optimal resuscitation strategy, which prevents or halts the progression of the trauma-induced coagulopathy, remains unknown. Although early and aggressive use of blood products in these patients appears to improve survival, over-enthusiastic resuscitative measures may not be the safest strategy.

This paper provides an overview of the classification of pelvic injuries and the current evidence on best-practice management of high-energy pelvic fractures, including resuscitation, transfusion of blood components, monitoring of coagulopathy, and procedural interventions including pre-peritoneal pelvic packing, external fixation and angiographic embolisation.

Cite this article: Bone Joint J 2014; 96-B:1143–54.

Tranexamic acid (TXA) has been used to reduce blood loss during total hip arthroplasty (THA), but its use could increase the risk of venous thromboembolic disease (VTE). Several studies have reported that TXA does not increase the prevalence of deep vein thrombosis (DVT), but most of those used routine chemical thromboprophylaxis, thereby masking the potential increased risk of TXA on VTE. We wished to ascertain whether TXA increases the prevalence of VTE in patients undergoing THA without routine chemical thromboprophylaxis. We carried out a retrospective case-control study in 254 patients who underwent a primary THA, 127 of whom received TXA (1 g given pre-operatively) and a control group of 127 who did not. All patients had mechanical but no chemical thomboprophylaxis. Each patient was examined for DVT by bilateral ultrasonography pre-operatively and on post-operative days 1 and 7. TXA was found to statistically significantly increase the incidence of total DVT on post-operative day 7 compared with the control group (24 (18.9%) and 12 (9.4%), respectively; p < 0.05) but most cases of DVT were isolated distal DVT, with the exception of one patient with proximal DVT in each group. One patient in the control group developed a non-fatal symptomatic pulmonary embolism (PE). The use of TXA did not appear to affect the prevalence of either proximal DVT or PE.

Cite this article: Bone Joint J 2015; 97-B:458–62.

Objectives

The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery.

Aims

Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA).

Aims

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses.

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.

MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We hypothesised that the functions of certain miRNAs and changes to their patterns of expression may be crucial in the pathogenesis of nonunion. Healing fractures and atrophic nonunions produced by periosteal cauterisation were created in the femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven, ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR analysis further revealed that, in nonunion, the expression levels of all five of these miRNAs peaked on day 14 and declined thereafter.

Our results suggest that miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an important role in the development of nonunion. These findings add to the understanding of the molecular mechanism for nonunion formation and may lead to the development of novel therapeutic strategies for its treatment.

Cite this article: Bone Joint J 2015; 97-B:1144–51.

We describe our technique and rationale using hybrid fixation for primary total hip arthroplasty (THA) at the Hospital for Special Surgery. Modern uncemented acetabular components have few screw holes, or no holes, polished inner surfaces, improved locking mechanisms, and maximised thickness and shell-liner conformity. Uncemented sockets can be combined with highly cross-linked polyethylene liners, which have demonstrated very low wear and osteolysis rates after ten to 15 years of implantation. The results of cement fixation with a smooth or polished surface finished stem have been excellent, virtually eliminating complications seen with cementless fixation like peri-operative femoral fractures and thigh pain. Although mid-term results of modern cementless stems are encouraging, the long-term data do not show reduced revision rates for cementless stems compared with cemented smooth stems. In this paper we review the conduct of a hybrid THA, with emphasis on pre-operative planning, surgical technique, hypotensive epidural anaesthesia, and intra-operative physiology.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):54–9.