Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Objectives. Wound complications are reported in up to 10% hip and knee arthroplasties and there is a proven association between wound complications and deep prosthetic infections. In this randomised controlled trial (RCT) we explore the potential benefits of a portable, single use, incisional negative pressure wound therapy dressing (iNPWTd) on wound exudate, length of stay (LOS), wound complications, dressing changes and cost-effectiveness following total hip and knee arthroplasties. Methods. A total of 220 patients undergoing elective primary total hip and knee arthroplasties were recruited into in a non-blinded RCT. For the final analysis there were 102 patients in the study group and 107 in the control group. Results. An improvement was seen in the study (iNPWTd) group compared to control in all areas. Peak post-surgical wound exudate was significantly reduced (p = 0.007). Overall LOS reduction (0.9 days, 95% confidence interval (CI) -0.2 to 2.5) was not significant (p = 0.07) but there was a significant reduction in patients with extreme values of LOS in the iNPWTd group (Moses test, p = 0.003). There was a significantly reduced number of dressing changes (mean difference 1.7, 95% CI 0.8 to 2.5, p = 0.002), and a trend to a significant four-fold reduction in reported post-operative surgical wound complications (8.4% control; 2.0% iNPWTd, p = 0.06). Conclusions. Based on the results of this RCT incisional negative pressure wound therapy dressings have a beneficial role in patients undergoing primary hip and knee arthroplasty to achieve predictable length of stay, especially to eliminate excessive hospital stay, and minimise wound complications. Cite this article: S. L. Karlakki, A. K. Hamad, C. Whittall, N. M. Graham, R. D. Banerjee, J. H. Kuiper. Incisional negative pressure wound therapy dressings (iNPWTd) in routine primary hip and knee arthroplasties: A randomised controlled trial. Bone Joint Res 2016;5:328–337. DOI: 10.1302/2046-3758.58.BJR-2016-0022.R1

We carried out a prospective, randomised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years (32.5 to 67.3). All were to undergo arthroscopic removal of the calcific deposit within six months after randomisation. The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone. In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm. 2. was applied. The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and standardised radiographs. The mean follow-up was 4.1 months and no patient was lost to follow-up. Both groups had significant improvement in their Constant shoulder score. Radiographs showed disappearance of the calcific deposit in 60.0% of the shoulders in group I and in 32.5% of group II (p < 0.05). Significantly better clinical and radiological results were obtained in group I than in group II. Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II. No severe side-effects were recorded. Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis, giving significantly higher rates of elimination of the calcium deposits, better clinical results and reduction in the need for surgery

We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy. . We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement. . There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post-operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; . sd. 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively. Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

All major studies have incorporated the use of prolonged courses of parenteral or oral antibiotic therapy in the management of two-stage revision of an infected total knee arthroplasty. We present a series of 59 consecutive patients, all with microbiologically-proven deep infection of a total knee arthroplasty, in whom a prolonged course of antibiotic therapy was not routinely used. The mean follow-up was 56.4 months (24 to 114). Of the 38 patients who underwent a staged exchange, infection was successfully eradicated in 34 (89%) but recurrent or persistent infection was present in four (11%). Our rate of cure for infection is similar to that reported elsewhere. We conclude that a prolonged course of antibiotic therapy seems not to alter the incidence of recurrent or persistent infection. The costs of the administration of antibiotics are high and such a regime may be unnecessary

Aims. This study sought to compare the rate of deep surgical site infection (SSI), as measured by the Centers for Disease Control and Prevention (CDC) definition, after surgery for a fracture of the hip between patients treated with standard dressings and those treated with incisional negative pressure wound therapy (iNPWT). Secondary objectives included determining the rate of recruitment and willingness to participate in the trial. Methods. The study was a two-arm multicentre randomized controlled feasibility trial that was embedded in the World Hip Trauma Evaluation cohort study. Any patient aged > 65 years having surgery for hip fracture at five recruitment centres in the UK was considered to be eligible. They were randomly allocated to have either a standard dressing or iNPWT after closure of the wound. The primary outcome measure was deep SSI at 30 and 90 days, diagnosed according to the CDC criteria. Secondary outcomes were: rate of recruitment; further surgery within 120 days; health-related quality of life (HRQoL) using the EuroQol five-level five-dimension questionnaire (EQ-5D-5L); and related complications within 120 days as well as mobility and residential status at this time. Results. A total of 462 valid randomizations were carried out (232 and 230 in the standard dressing and iNPWT groups, respectively). In the standard dressing group, 14 of 218 patients (6.4%) developed deep SSI. In the iNPWT group, four of 214 patients (1.9%) developed deep SSI. This gives a total rate of SSI of 4.2% (95% confidence interval (CI) 2.7% to 6.5%). Patients and surgeons were willing to participate in the study with 462 patients being recruited from a possible 749 (62.3%). Conclusion. The rate of deep SSI 30 days after surgery for a fracture of the hip was 4%, which makes a study comparing the clinical effectiveness of standard dressings and iNPWT feasible. Cite this article: Bone Joint J 2021;103-B(4):755–761

Aims. To compare the cost-utility of standard dressing with incisional negative-pressure wound therapy (iNPWT) in adults with closed surgical wounds associated with major trauma to the lower limbs. Methods. A within-trial economic evaluation was conducted from the UK NHS and personal social services (PSS) perspective based on data collected from the Wound Healing in Surgery for Trauma (WHiST) multicentre randomized clinical trial. Health resource utilization was collected over a six-month post-randomization period using trial case report forms and participant-completed questionnaires. Cost-utility was reported in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was conducted to test the robustness of cost-effectiveness estimates while uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves. Results. The incremental cost of standard dressing versus iNPWT over six months was £2,037 (95% confidence interval (CI) £349 to £3,724). There was an insignificant increment in QALYs gained in the iNPWT group (0.005, 95% CI -0.018 to 0.028). The probability of iNPWT being cost-effective at £20,000 per QALY was 1.9%. The results remained robust in the sensitivity analysis. Conclusion. The within-trial economic evaluation suggests that iNPWT is unlikely to be a cost-effective alternative to standard dressing in adults with closed surgical wounds to their lower limbs. Cite this article: Bone Joint J 2020;102-B(8):1072–1081

Aims. The aim of this study was to estimate the cost-effectiveness of negative-pressure wound therapy (NPWT) in comparison with standard wound management after initial surgical wound debridement in adults with severe open fractures of the lower limb. Patients and Methods. An economic evaluation was conducted from the perspective of the United Kingdom NHS and Personal Social Services, based on evidence from the 460 participants in the Wound Management of Open Lower Limb Fractures (WOLLF) trial. Economic outcomes were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Bivariate regression of costs (given in £, 2014 to 2015 prices) and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained associated with NPWT dressings. Sensitivity and subgroup analyses were undertaken to assess the impacts of uncertainty and heterogeneity, respectively, surrounding aspects of the economic evaluation. Results. The base case analysis produced an incremental cost-effectiveness ratio of £267 910 per QALY gained, reflecting higher costs on average (£678; 95% confidence interval (CI) -£1082 to £2438) and only marginally higher QALYS (0.002; 95% CI -0.054 to 0.059) in the NPWT group. The probability that NPWT is cost-effective in this patient population did not exceed 27% regardless of the value of the cost-effectiveness threshold. This result remained robust to several sensitivity and subgroup analyses. Conclusion. This trial-based economic evaluation suggests that NPWT is unlikely to be a cost-effective strategy for improving outcomes in adult patients with severe open fractures of the lower limb. Cite this article: Bone Joint J 2019;101-B:1392–1401

Limb salvage involving wide resection and reconstruction is now well established for managing musculoskeletal sarcomas. However, involvement of major nerves and vessels with a large volume of muscle and skin may result in a useless limb, contributing to depression and a low quality of life. We have been studying alternative treatments for musculoskeletal sarcoma since 1990, and have recently established a regime using photodynamic surgery with cells labelled with acridine orange, photodynamic therapy with cells treated similarly and radiodynamic treatment using the effect of X-rays on such cells. These techniques have been used after marginal or intralesional resection of tumours since 1999 and have enabled maintenance of excellent limb function in patients with sarcomas

We carried out a retrospective review over ten months of patients who had presented with a low-energy subtrochanteric fracture. We identified 13 women of whom nine were on long-term alendronate therapy and four were not. The patients treated with alendronate were younger, with a mean age of 66.9 years (55 to 82) vs 80.3 years (64 to 92) and were more socially active. The fractures sustained by the patients in the alendronate group were mainly at the femoral metaphyseal-diaphyseal junction and many had occurred after minimal trauma. Five of these patients had prodromal pain in the affected hip in the months preceding the fall, and three demonstrated a stress reaction in the cortex in the contralateral femur. Our study suggests that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur. We believe that this finding is important and indicates the need for caution in the long-term use of alendronate in the treatment of osteoporosis

1. A study of 2,200 patients receiving electro-convulsive therapy showed that fifty-three sustained fractures or dislocations—an incidence of 2·4 per cent. Of the fifty-three injuries, twenty-one occurred in the spine, fifteen in the neck of femur, fifteen in the upper end of humerus, one in the coracoid process; one dislocated jaw required anaesthesia for its reduction (other cases of transient dislocation of the jaw are excluded). 2. The incidence, site, and type of spinal fractures are recorded, and the relation of the fracture to the first convulsion is noted. No late changes were found in the spines of patients examined two years or more after treatment. A neutral position of the spine during the convulsion is believed to diminish the risk of fracture. 3. Fracture of the neck of the femur is a serious injury in these patients. In one case the injury was bilateral. 4. The fifteen cases of fracture-dislocation of the upper humerus are analysed. They included two cases of posterior dislocation of the humeral head; the possible mechanism of this is explained and a method of prevention suggested. 5. Fifty-three patients with chronic epilepsy with psychosis were examined. Four cases of fractured spine were discovered. The site of fracture was different from that of fractures caused by convulsive therapy and a reason for this is suggested. The type and mechanism of the fracture are similar in the two groups

We present a series of 114 patients with microbiologically-proven chronically-infected total hip replacement, treated between 1991 and 2004 by a two-stage exchange procedure with antibiotic-loaded cement, but without the use of a prolonged course of antibiotic therapy. The mean follow-up for all patients was 74 months (2 to 175) with all surviving patients having a minimum follow-up of two years. Infection was successfully eradicated in 100 patients (87.7%), a rate which is similar to that reported by others, but where prolonged adjuvant antibiotic therapy has been used. Using the technique described, a prolonged course of systemic antibiotics does not appear to be essential and the high cost of the administration of antibiotics can be avoided

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). . Methods. We undertook a literature review of this emerging indication to identify evidence within orthopaedic surgery and other surgical disciplines. Literature that supports our current understanding of the mechanisms of action was also reviewed in detail. . Results. A total of 33 publications were identified, including nine clinical study reports from orthopaedic surgery; four from cardiothoracic surgery and 12 from studies in abdominal, plastic and vascular disciplines. Most papers (26 of 33) had been published within the past three years. Thus far two randomised controlled trials – one in orthopaedic and one in cardiothoracic surgery – show evidence of reduced incidence of wound healing complications after between three and five days of post-operative NPWT of two- and four-fold, respectively. Investigations show that reduction in haematoma and seroma, accelerated wound healing and increased clearance of oedema are significant mechanisms of action. . Conclusions. There is a rapidly emerging literature on the effect of NPWT on the closed incision. Initiated and confirmed first with a randomised controlled trial in orthopaedic trauma surgery, studies in abdominal, plastic and vascular surgery with high rates of complications have been reported recently. The evidence from single-use NPWT devices is accumulating. There are no large randomised studies yet in reconstructive joint replacement. Cite this article: Bone Joint Res 2013;2:276–84

Avascular necrosis of bone is a well-recognised phenomenon in patients on long-term steroid therapy, especially after renal transplantation. There are only four cases reported in the literature of multifocal avascular necrosis after short-term high-dose steroid therapy, and three additional cases are reported in this paper. All the hips have needed reconstructive surgery within two and a half years of the onset of symptoms; in one patient, however, this has been prevented by other medical problems. In two of the three patients reported in this paper the shoulders also were affected; eventually they became pain-free but movement was restricted. Short-term high-dose steroid therapy has only recently been recognised as a cause of avascular necrosis and attempts should be made to prevent the incidence increasing

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.