Aims. Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. Patients and Methods. This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. Results. A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). ‘Typical’ symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). Conclusion. Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119–24

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This ‘bone-healing unit’ produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff’s law, Perren’s strain theory and Frost’s concept of the “mechanostat”. In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture – healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884–91

Aims. The aim of this study was to assess the current trends in the estimation of survival and the preferred forms of treatment of pathological fractures among national and international general and oncological orthopaedic surgeons, and to explore whether improvements in the management of these patients could be identified in this way. Materials and Methods. All members of the Dutch Orthopaedic Society (DOS) and the European Musculoskeletal Oncology Society (EMSOS) were invited to complete a web-based questionnaire containing 12 cases. Results. A total of 96 of 948 members of the DOS (10.1%; groups 1 and 2) and 33 of 182 members of the EMSOS (18%; group 3) replied. The estimation of survival was accurate by more than 50% of all three groups, if the expected survival was short (< 3 months) or long (> 12 months). General orthopaedic surgeons preferred using an intramedullary nail for fractures of the humerus and femur, irrespective of the expected survival or the origin of primary tumour or the location of the fracture. Oncological orthopaedic surgeons recommended prosthetic reconstruction in patients with a long expected survival. Conclusion. Identifying patients who require centralized care, as opposed to those who can be adequately treated in a regional centre, can improve the management of patients with pathological fractures. This differentiation should be based on the expected survival, the type and extent of the tumour, and the location of the fracture. Cite this article: Bone Joint J 2018;100-B:1392–8

Aims. The primary aim of this study was to determine the morbidity of a tibial strut autograft and characterize the rate of bony union following its use. Patients and Methods. We retrospectively assessed a series of 104 patients from a single centre who were treated with a tibial strut autograft of > 5 cm in length. A total of 30 had a segmental reconstruction with continuity of bone, 27 had a segmental reconstruction without continuity of bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity was defined as any event that required a modification of the postoperative management. Union was assessed clinically and radiologically at a median of 36 months (IQR, 14 to 74). Results. Donor-site morbidity occurred in four patients (4%; 95% confidence interval (CI) 1 to 10). One patient had a stress fracture of the tibia, which healed with a varus deformity, requiring an osteotomy. Two patients required evacuation of a haematoma and one developed anterior compartment syndrome which required fasciotomies. The cumulative probability of union was 90% (95% CI 80 to 96) at five years. The type of reconstruction (p = 0.018), continuity of bone (p = 0.006) and length of tibial graft (p = 0.037) were associated with the time to union. Conclusion. The tibial strut autograft has a low risk of morbidity and provides adequate bone stock for treating various defects of long bones. Cite this article: Bone Joint J 2018;100-B:667–74

Extracorporeal irradiation of an excised tumour-bearing segment of bone followed by its re-implantation is a technique used in bone sarcoma surgery for limb salvage when the bone is of reasonable quality. There is no agreement among previous studies about the dose of irradiation to be given: up to 300 Gy have been used. We investigated the influence of extracorporeal irradiation on the elastic and viscoelastic properties of bone. Bone was harvested from mature cattle and subdivided into 13 groups: 12 were exposed to increasing levels of irradiation: one was not and was used as a control. The specimens, once irradiated, underwent mechanical testing in saline at 37°C. The mechanical properties of each group, including Young’s modulus, storage modulus and loss modulus, were determined experimentally and compared with the control group. . There were insignificant changes in all of these mechanical properties with an increasing level of irradiation. . We conclude that the overall mechanical effect of high levels of extracorporeal irradiation (300 Gy) on bone is negligible. Consequently the dose can be maximised to reduce the risk of local tumour recurrence. Cite this article: Bone Joint J 2015;97-B:1152–6

Objectives. The monitoring of fracture healing is a complex process. Typically, successive radiographs are performed and an emerging calcification of the fracture area is evaluated. The aim of this study was to investigate whether different bone healing patterns can be distinguished using a telemetric instrumented femoral internal plate fixator. Materials and Methods. An electronic telemetric system was developed to assess bone healing mechanically. The system consists of a telemetry module which is applied to an internal locking plate fixator, an external reader device, a sensor for measuring externally applied load and a laptop computer with processing software. By correlation between externally applied load and load measured in the implant, the elasticity of the osteosynthesis is calculated. The elasticity decreases with ongoing consolidation of a fracture or nonunion and is an appropriate parameter for the course of bone healing. At our centre, clinical application has been performed in 56 patients suffering nonunion or fracture of the femur. Results. A total of 39 cases of clinical application were reviewed for this study. In total, four different types of healing curves were observed: fast healing; slow healing; plateau followed by healing; and non-healing. Conclusion. The electronically instrumented internal fixator proved to be valuable for the assessment of bone healing in difficult healing situations. Cost-effective manufacturing is possible because the used electronic components are derived from large-scale production. The incorporation of microelectronics into orthopaedic implants will be an important innovation in future clinical care. Cite this article: B. Kienast, B. Kowald, K. Seide, M. Aljudaibi, M. Faschingbauer, C. Juergens, J. Gille. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–197. DOI: 10.1302/2046-3758.55.2000611

Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions. This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1

The best method of managing a fracture of the distal humerus in a frail low-demand patient with osteoporotic bone remains controversial. Total elbow arthroplasty (TEA) has been recommended for patients in whom open reduction and internal fixation (ORIF) is not possible. Conservative methods of treatment, including the ‘bag of bones’ technique (acceptance of displacement of the bony fragments and early mobilisation), are now rarely considered as they are believed to give a poor functional result. We reviewed 40 elderly and low-demand patients (aged 50 to 93 years, 72% women) with a fracture of the distal humerus who had been treated conservatively at our hospital between March 2008 and December 2013, and assessed their short- and medium-term functional outcome. . In the short-term, the mean Broberg and Morrey score improved from 42 points (poor; 23 to 80) at six weeks after injury to 67 points (fair; 40 to 88) by three months. . In the medium-term, surviving patients (n = 20) had a mean Oxford elbow score of 30 points (7 to 48) at four years and a mean Disabilities of the Arm, Shoulder and Hand score of 38 points (0 to 75): 95% reported a functional range of elbow flexion. The cumulative rate of fracture union at one year was 53%. The mortality at five years approached 40%. . Conservative management of a fracture of the distal humerus in a low-demand patient only gives a modest functional result, but avoids the substantial surgical risks associated with primary ORIF or TEA. Cite this article: Bone Joint J 2015;97-B:1132–8

Objective. The main object of this study was to use a geometric morphometric approach to quantify the left-right symmetry of talus bones. . Methods. Analysis was carried out using CT scan images of 11 pairs of intact tali. Two important geometric parameters, volume and surface area, were quantified for left and right talus bones. The geometric shape variations between the right and left talus bones were also measured using deviation analysis. Furthermore, location of asymmetry in the geometric shapes were identified. . Results. Numerical results showed that talus bones are bilaterally symmetrical in nature, and the difference between the surface area of the left and right talus bones was less than 7.5%. Similarly, the difference in the volume of both bones was less than 7.5%. Results of the three-dimensional (3D) deviation analyses demonstrated the mean deviation between left and right talus bones were in the range of -0.74 mm to 0.62 mm. It was observed that in eight of 11 subjects, the deviation in symmetry occurred in regions that are clinically less important during talus surgery. . Conclusions. We conclude that left and right talus bones of intact human ankle joints show a strong degree of symmetry. The results of this study may have significance with respect to talus surgery, and in investigating traumatic talus injury where the geometric shape of the contralateral talus can be used as control. Cite this article: Bone Joint Res 2014;3:139–45

Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262

Aims. In the 1990s, a bioactive bone cement (BABC) containing apatite-wollastonite glass-ceramic (AW-GC) powder and bisphenol-a-glycidyl methacrylate resin was developed at our hospital. In 1996, we used BABC to fix the acetabular component in primary total hip arthroplasty (THA) in 20 patients as part of a clinical trial. The purpose of this study was to investigate the long-term results of primary THA using BABC. Patients and Methods. A total of 20 patients (three men and 17 women) with a mean age of 57.4 years (40 to 71), a mean body weight of 52.3 kg (39 to 64), and a mean body mass index (BMI) of 23.0 kg/m. 2. (19.8 to 28.6) were evaluated clinically and radiologically. Survival analyses were undertaken, and wear analyses were carried out using a computer-aided method. Results. The mean follow-up was 17.6 years (1.5 to 21.1). Radiological loosening occurred in four sockets with aseptic loosening at a mean of 7.8 years (1.5 to 20.7). Kaplan–Meier survival analyses using revision of the acetabular component, radiological loosening of the acetabular component, and the worst-case scenario with revision of the acetabular component to include the two patients lost to follow-up as endpoints yielded survival rates of 94.7%, 84.4%, and 85.0% at ten years, and 70.0%, 84.4%, and 62.8% at 20 years, respectively. Wear analysis revealed a mean linear wear rate of 0.068 mm per year. Conclusion. The long-term results of primary THAs using BABC were unsatisfactory. Its brittle nature and poor handling properties need to be improved before it becomes an alternative method of fixing the acetabular component in cemented THA. Cite this article: Bone Joint J 2019;101-B:787–792

Aims. The aims of this study were to evaluate the long-term outcome of surgery for bone or soft-tissue metastases from renal cell carcinoma (RCC) and to determine factors that affect prognosis. Patients and Methods. Between 1993 and 2014, 58 patients underwent surgery for bone or soft-tissue metastases from RCC at our hospital. There were 46 men and 12 women with a mean age of 60 years (25 to 84). The mean follow-up period was 52 months (1 to 257). The surgical sites included the spine (33 patients), appendicular skeleton (ten patients), pelvis (eight patients), thorax (four patients), and soft tissue (three patients). The surgical procedures were en bloc metastasectomy in 46 patients (including 33 patients of total en bloc spondylectomy (TES)) and intralesional curettage in 12 patients. These patients were retrospectively evaluated for factors associated with prognosis. Results. The one-, three-, five-, ten-, and 15-year overall survival (OS) rates were 89%, 75%, 62%, 48%, and 25%, respectively. The median survival time (MST) was 127 months for en bloc metastasectomy and 54 months for intralesional curettage and bone grafting. The median survival time was 127 months for the spine, 140 months for lesions of the appendicular skeleton, and 54 months for the pelvis. Multivariate analysis showed that non-clear cell type RCC and metastases to more than two sites were independent risk factors for a poor prognosis. Conclusion. Patients with bone or soft-tissue metastases from a RCC have a reasonable prognosis, making surgical resection a viable option even in patients in whom the metastases are advanced. Cite this article: Bone Joint J 2018;100-B:1241–8

Objectives. The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. Methods. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included. Results. The literature search resulted in 823 manuscripts of which 64 manuscripts met the final inclusion criteria. The included manuscripts consisted of four randomised controlled trials (level I), eight cohort studies (level III) and 49 case-series (level IV). No clinical studies were found for ten DBM products, and most DBM products were only used in combination with other grafting materials. DBM products were most extensively investigated in spinal surgery, showing limited level I evidence that supports the use Grafton DBM (Osteotech, Eatontown, New Jersey) as a bone graft extender in posterolateral lumbar fusion surgery. DBM products are not thoroughly investigated in trauma surgery, showing mainly level IV evidence that supports the use of Allomatrix (Wright Medical, London, United Kingdom), DBX (DePuy Synthes, Zuchwil, Switzerland), Grafton DBM, or OrthoBlast (Citagenix Laval, Canada) as bone graft extenders. Conclusions. The clinical level of evidence that supports the use of DBM in trauma and orthopaedic surgery is limited and consists mainly of poor quality and retrospective case-series. More prospective, randomised controlled trials are needed to understand the clinical effect and impact of DBM in trauma and orthopaedic surgery. Cite this article: J. van der Stok, K. A. Hartholt, D. A. L. Schoenmakers, J. J. C. Arts. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery: A systemati c review. Bone Joint Res 2017;6:423–432. DOI: 10.1302/2046-3758.67.BJR-2017-0027.R1

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

Aims. Adjuvant treatment after intralesional curettage for atypical cartilaginous tumours (ACTs) of long bones is widely accepted for extending surgical margins. However, evaluating the isolated effect of adjuvant treatment is difficult, and it is unclear whether not using such adjuvants provides poor oncological outcomes. Hence, we analyzed whether intralesional curettage without cryosurgery or chemical adjuvants provides poor oncological outcomes in patients with an ACT. Patients and Methods. A total of 24 patients (nine men, 15 women) (mean age 45 years; 18 to 62) were treated for ACTs of long bones and followed up for a median of 66 months (interquartile range 50 to 84). All patients were treated with extensive manual curettage and limited burring. Bone cement and grafts were used to fill bone defects in 16 and eight patients, respectively. No chemical adjuvants or cryosurgery were used. Results. No local recurrence was detectable on plain radiographs and MRI or CT images. At the last follow-up, there were no distant metastases or disease-specific deaths. No procedure-related complications or postoperative fractures developed. Conclusion. Intralesional curettage without cryosurgery or chemical adjuvants may provide excellent oncological outcomes for patients with ACTs of long bones, without the risk of complications related to adjuvant use. Our investigation suggests thorough curettage alone is a reasonable treatment option for ACT. However, we acknowledge the limited size of our investigation warrants a multicentre collaborative study to confirm our findings. Cite this article: Bone Joint J 2018;100-B:256–61

Aims. The purpose of the study was to investigate whether closed intramedullary (IM) nailing with percutaneous cement augmentation is better than conventional closed nailing at relieving pain and suppressing tumours in patients with metastases of the femur and humerus. Patients and Methods. A total of 43 patients (27 men, 16 women, mean age 63.7 years, standard deviation (. sd. ) 12.2; 21 to 84) underwent closed IM nailing with cement augmentation for long bone metastases. A further 27 patients, who underwent conventional closed IM nailing, served as controls. Pain was assessed using a visual analogue scale (VAS) score pre-operatively (pre-operative VAS), one week post-operatively (immediate post-operative VAS), and at six weeks post-operatively (follow-up post-operative VAS). Progression of the tumour was evaluated in subgroups of patients using F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET)/computed tomography (CT) and/or bone scintigraphy (BS), at a mean of 8.8 and 7.2 months post-operatively, respectively. Results. The mean pain scores of patients who underwent closed nailing with cement augmentation were significantly lower than those of the control patients post-operatively (immediate post-operative VAS: 3.8, . sd. 0.9 versus 6.0, . sd. 0.9; follow-up post-operative VAS: 3.3, . sd. 2.5 versus 6.6, . sd. 2.2; all p < 0.001). The progression of the metastasis was suppressed in 50% (10/20) of patients who underwent closed nailing with augmentation, but in only 8% (1/13) of those in the control group. Conclusion. Percutaneous cement augmentation of closed IM nailing improves the relief of pain and limits the progression of the tumour in patients with metastases to the long bones. Take home message: Percutaneous cement augmentation while performing closed IM nailing has some advantages for long bone metastases. Cite this article: Bone Joint J 2016;98-B:703–9

Aims. This study reviews the use of a titanium mesh cage (TMC) as an adjunct to intramedullary nail or plate reconstruction of an extra-articular segmental long bone defect. Patients and Methods. A total of 17 patients (aged 17 to 61 years) treated for a segmental long bone defect by nail or plate fixation and an adjunctive TMC were included. The bone defects treated were in the tibia (nine), femur (six), radius (one), and humerus (one). The mean length of the segmental bone defect was 8.4 cm (2.2 to 13); the mean length of the titanium mesh cage was 8.3 cm (2.6 to 13). The clinical and radiological records of the patients were analyzed retrospectively. Results. The mean time to follow-up was 55 months (12 to 126). Overall, 16 (94%) of the patients achieved radiological filling of their bony defect and united to the native bone ends proximally and distally, resulting in a functioning limb. Complications included device failure in two patients (12%), infection in two (12%), and wound dehiscence in one (6%). Four patients (24%) required secondary surgery, four (24%) had a residual limb-length discrepancy, and one (6%) had a residual angular limb deformity. Conclusion. A titanium mesh cage is a useful adjunct in the treatment of an extra-articular segmental defect in a long bone. Cite this article: Bone Joint J 2018;100-B:646–51