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Bone & Joint Research
Vol. 5, Issue 4 | Pages 116 - 121
1 Apr 2016
Leow JM Clement ND Tawonsawatruk T Simpson CJ Simpson AHRW

Objectives. The radiographic union score for tibial (RUST) fractures was developed by Whelan et al to assess the healing of tibial fractures following intramedullary nailing. In the current study, the repeatability and reliability of the RUST score was evaluated in an independent centre (a) using the original description, (b) after further interpretation of the description of the score, and (c) with the immediate post-operative radiograph available for comparison. Methods. A total of 15 radiographs of tibial shaft fractures treated by intramedullary nailing (IM) were scored by three observers using the RUST system. Following discussion on how the criteria of the RUST system should be implemented, 45 sets (i.e. AP and lateral) of radiographs of IM nailed tibial fractures were scored by five observers. Finally, these 45 sets of radiographs were rescored with the baseline post-operative radiograph available for comparison. Results. The initial intraclass correlation (ICC) on the first 15 sets of radiographs was 0.67 (95% CI 0.63 to 0.71). However, the original description was being interpreted in different ways. After agreeing on the interpretation, the ICC on the second cohort improved to 0.75. The ICC improved even further to 0.79, when the baseline post-operative radiographs were available for comparison. Conclusion. This study demonstrates that the RUST scoring system is a reliable and repeatable outcome measure for assessing tibial fracture healing. Further improvement in the reliability of the scoring system can be obtained if the radiographs are compared with the baseline post-operative radiographs. Cite this article: Mr J.M. Leow. The radiographic union scale in tibial (RUST) fractures: Reliability of the outcome measure at an independent centre. Bone Joint Res 2016;5:116–121. DOI: 10.1302/2046-3758.54.2000628


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Methods

We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 585 - 593
1 Aug 2022
Graham SM Jalal MMK Lalloo DG Hamish R. W. Simpson A

Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims. This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. Methods. A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data. Results. After the screening, 44 studies were included with 1,079 patients and 1,083 segments of infected bone defects treated with the induced membrane technique. The mean defect size was 6.8 cm (0.5 to 30). After the index second stage procedure, 85% (797/942) of segments achieved union, and 92% (999/1,083) of segments achieved final healing. The multivariate analysis with data from 296 patients suggested that older age was associated with higher nonunion risk. Patients with external fixation in the second stage had a significantly higher risk of developing nonunion, increasing the need for additional procedures. The autografts harvested from the femur reamer-irrigator-aspirator increased nonunion, infection recurrence, and additional procedure rates. Conclusion. The induced membrane technique is an effective technique for treating infected bone defects. Internal fixation during the second stage might effectively promote bone healing and reduce additional procedures without increasing infection recurrence. Future studies should standardize individual patient data prospectively to facilitate research on the affected patient outcomes. Cite this article: Bone Joint Res 2023;12(9):546–558


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims. Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods. Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results. Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion. The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases. Cite this article: Bone Joint Res 2024;13(3):127–135


Bone & Joint Research
Vol. 10, Issue 12 | Pages 759 - 766
1 Dec 2021
Nicholson JA Oliver WM MacGillivray TJ Robinson CM Simpson AHRW

Aims. The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. Methods. A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC). Results. Nine of the ten patients achieved union at six months. At six weeks, seven patients had bridging callus of ≥ one cortex on the 3D reconstruction and when present all achieved union. Compared to six-week radiographs, no bridging callus was present in any patient. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8% sensitive and 100% specific to predict union). At 12 weeks, nine patients had bridging callus at ≥ one cortex on 3D reconstruction (100%-sensitive and 100%-specific to predict union). Presence of sonographic bridging callus on 3D reconstruction demonstrated excellent reviewer agreement on ICC at 0.87 (95% confidence interval 0.74 to 0.96). Conclusion. 3D fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of early fracture healing. Cite this article: Bone Joint Res 2021;10(12):759–766


Bone & Joint Research
Vol. 12, Issue 2 | Pages 138 - 146
14 Feb 2023
Aquilina AL Claireaux H Aquilina CO Tutton E Fitzpatrick R Costa ML Griffin XL

Aims. Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years. Methods. Systematic literature searches identified all clinical studies reporting outcomes for adults following open lower limb fracture between January 2009 and July 2019. All outcomes and outcome measurement instruments were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using an outcome taxonomy. Results. A total of 532 eligible studies were identified, reporting 1,803 outcomes with 786 unique outcome terms, which collapsed to 82 standardized outcome headings. Overall 479 individual outcome measurement instruments were identified, including 298 outcome definitions, 27 patient- and 18 clinician-reported outcome measures, and six physical performance measures. The most-reported outcome was ‘bone union/healing’ reported in over 50% of included studies, while health-related quality of life was only measured in 6% of included studies. Conclusion. Outcomes reported for people recovering from open lower limb fracture are heterogeneous, liable to outcome reporting bias, and vary widely in the definitions and the measurement tools used to collect them. Outcomes likely to be important to patients, such as quality of life and measures of physical functioning, have been neglected. This systematic review identifies the need to unify outcome measures reported on patients recovering from open lower limb fracture; this may be addressed by creating a core outcome set. Cite this article: Bone Joint Res 2023;12(2):138–146


Bone & Joint Research
Vol. 10, Issue 2 | Pages 113 - 121
1 Feb 2021
Nicholson JA Oliver WM MacGillivray TJ Robinson CM Simpson AHRW

Aims. To evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus on ultrasound. Methods. Adult patients managed nonoperatively with a displaced mid-shaft clavicle were recruited prospectively. Ultrasound evaluation of the fracture was undertaken to determine if sonographic bridging callus was present. Clinical risk factors at six weeks were used to stratify patients at high risk of nonunion with a combination of Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) ≥ 40, fracture movement on examination, or absence of callus on radiograph. Results. A total of 112 patients completed follow-up at six months with a nonunion incidence of 16.7% (n = 18/112). Sonographic bridging callus was detected in 62.5% (n = 70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n = 69/70). If absent, nonunion developed in 40.5% of cases (n = 17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Regression analysis found that failure to detect sonographic bridging callus at six weeks was associated with older age, female sex, simple fracture pattern, smoking, and greater fracture displacement (Nagelkerke R. 2. = 0.48). Of the cohort, 30.4% (n = 34/112) had absent sonographic bridging callus in addition to one or more of the clinical risk factors at six weeks that predispose to nonunion. If one was present the nonunion rate was 35%, 60% with two, and 100% when combined with all three. Conclusion. Ultrasound combined with clinical risk factors can accurately predict fracture healing at six weeks following a displaced midshaft clavicle fracture. Cite this article: Bone Joint Res 2021;10(2):113–121


Bone & Joint Research
Vol. 10, Issue 10 | Pages 659 - 667
1 Oct 2021
Osagie-Clouard L Meeson R Sanghani-Kerai A Bostrom M Briggs T Blunn G

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667


Bone & Joint Research
Vol. 13, Issue 11 | Pages 647 - 658
12 Nov 2024
Li K Zhang Q

Aims. The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures. Methods. A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively. Results. Compared with the control group, the ERAS group had a shorter operating time, hospital stay, preoperative waiting time, postoperative discharge time, less intraoperative blood loss, and higher albumin and haemoglobin on the first postoperative day. The time to removal of the urinary catheter/drainage tube was shortened, and the drainage volume was also significantly reduced in the ERAS group. There was no significant difference in the visual analogue scale (VAS) scores on postoperative return to the ward, but the ERAS group had lower scores on the first, second, and third postoperative days. There were no significant differences in the incidence of complications, other than 10% more nausea and vomiting in the control group. The limb function scores at one-year follow-up were similar between the two groups, but time to radiological fracture union and time to return to physical work and sports were significantly reduced in the ERAS group. Conclusion. The implementation of a series of perioperative nursing measures based on the concept of ERAS in PLWH with limb fracture can significantly reduce the operating time and intraoperative blood loss, reduce the occurrence of postoperative pain and complications, and accelerate the improvement of the functional status of the affected limb in the early stage, which is worthy of applying in more medical institutions. Cite this article: Bone Joint Res 2024;13(11):647–658


Bone & Joint Research
Vol. 8, Issue 7 | Pages 304 - 312
1 Jul 2019
Nicholson JA Tsang STJ MacGillivray TJ Perks F Simpson AHRW

Objectives. The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. Methods. A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”. Results. The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. Conclusion. Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing. Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304–312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Methods

Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).


Bone & Joint Research
Vol. 12, Issue 7 | Pages 412 - 422
4 Jul 2023
Ferguson J Bourget-Murray J Hotchen AJ Stubbs D McNally M

Aims

Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

Methods

A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 256 - 258
3 Apr 2023
Farrow L Evans J

Cite this article: Bone Joint Res 2023;12(4):256–258.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 507 - 512
18 Sep 2024
Farrow L Meek D Leontidis G Campbell M Harrison E Anderson L

Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework – a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.

Cite this article: Bone Joint Res 2024;13(9):507–512.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 588 - 595
17 Oct 2024
Breu R Avelar C Bertalan Z Grillari J Redl H Ljuhar R Quadlbauer S Hausner T

Aims

The aim of this study was to create artificial intelligence (AI) software with the purpose of providing a second opinion to physicians to support distal radius fracture (DRF) detection, and to compare the accuracy of fracture detection of physicians with and without software support.

Methods

The dataset consisted of 26,121 anonymized anterior-posterior (AP) and lateral standard view radiographs of the wrist, with and without DRF. The convolutional neural network (CNN) model was trained to detect the presence of a DRF by comparing the radiographs containing a fracture to the inconspicuous ones. A total of 11 physicians (six surgeons in training and five hand surgeons) assessed 200 pairs of randomly selected digital radiographs of the wrist (AP and lateral) for the presence of a DRF. The same images were first evaluated without, and then with, the support of the CNN model, and the diagnostic accuracy of the two methods was compared.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 179 - 188
7 Mar 2023
Itoh M Itou J Imai S Okazaki K Iwasaki K

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

Methods

Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 409 - 412
22 Jun 2022
Tsang SJ Ferreira N Simpson AHRW


Bone & Joint Research
Vol. 13, Issue 1 | Pages 40 - 51
11 Jan 2024
Lin J Suo J Bao B Wei H Gao T Zhu H Zheng X

Aims

To investigate the efficacy of ethylenediaminetetraacetic acid-normal saline (EDTA-NS) in dispersing biofilms and reducing bacterial infections.

Methods

EDTA-NS solutions were irrigated at different durations (1, 5, 10, and 30 minutes) and concentrations (1, 2, 5, 10, and 50 mM) to disrupt Staphylococcus aureus biofilms on Matrigel-coated glass and two materials widely used in orthopaedic implants (Ti-6Al-4V and highly cross-linked polyethylene (HXLPE)). To assess the efficacy of biofilm dispersion, crystal violet staining biofilm assay and colony counting after sonification and culturing were performed. The results were further confirmed and visualized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). We then investigated the efficacies of EDTA-NS irrigation in vivo in rat and pig models of biofilm-associated infection.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 559 - 572
8 Oct 2024
Wu W Zhao Z Wang Y Liu M Zhu G Li L

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Methods

A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 386 - 397
22 Jun 2022
Zhu D Fang H Yu H Liu P Yang Q Luo P Zhang C Gao Y Chen Y

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Methods

MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 803 - 813
1 Nov 2022
Guan X Gong X Jiao ZY Cao HY Liu S Lin C Huang X Lan H Ma L Xu B

Aims

The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

Methods

Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 541 - 547
17 Aug 2022
Walter N Hierl K Brochhausen C Alt V Rupp M

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Methods

Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 239 - 250
20 Apr 2022
Stewart CC O’Hara NN Bzovsky S Bahney CS Sprague S Slobogean GP

Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Methods

A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 561 - 574
10 Aug 2022
Schulze-Tanzil GG Delgado Cáceres M Stange R Wildemann B Docheva D

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 210 - 213
1 Apr 2022
Fontalis A Haddad FS


Bone & Joint Research
Vol. 10, Issue 12 | Pages 840 - 843
15 Dec 2021
Al-Hourani K Tsang SJ Simpson AHRW


Bone & Joint Research
Vol. 10, Issue 12 | Pages 807 - 819
1 Dec 2021
Wong RMY Wong PY Liu C Chung YL Wong KC Tso CY Chow SK Cheung W Yung PS Chui CS Law SW

Aims

The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing.

Methods

A literature search was performed in PubMed, Embase, and Web of Science databases. The keywords used for the search criteria were ((3d print*) OR (rapid prototyp*) OR (additive manufactur*)) AND (orthopaedic). The inclusion criteria were: 1) use of 3D printing in orthopaedics, 2) randomized controlled trials, and 3) studies with participants/patients. Risk of bias was assessed with Cochrane Collaboration Tool and PEDro Score. Pooled analysis was performed.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 91 - 101
1 Feb 2022
Munford MJ Stoddart JC Liddle AD Cobb JP Jeffers JRT

Aims

Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Methods

In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 714 - 722
1 Nov 2021
Qi W Feng X Zhang T Wu H Fang C Leung F

Aims

To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model.

Methods

A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme.


Objectives. The annual incidence of hip fracture is 620 000 in the European Union. The cost of this clinical problem has been estimated at 1.75 million disability-adjusted life years lost, equating to 1.4% of the total healthcare burden in established market economies. Recent guidance from The National Institute for Health and Clinical Excellence (NICE) states that research into the clinical and cost effectiveness of total hip arthroplasty (THA) as a treatment for hip fracture is a priority. We asked the question: can a trial investigating THA for hip fracture currently be delivered in the NHS?. Methods. We performed a contemporaneous process evaluation that provides a context for the interpretation of the findings of WHiTE Two – a randomised study of THA for hip fracture. We developed a mixed methods approach to situate the trial centre within the context of wider United Kingdom clinical practice. We focused on fidelity, implementation, acceptability and feasibility of both the trial processes and interventions to stakeholder groups, such as healthcare providers and patients. Results. We have shown that patients are willing to participate in this type of research and that surgeons value being part of a team that has a strong research ethos. However, surgical practice does not currently reflect NICE guidance. Current models of service delivery for hip fractures are unlikely to be able to provide timely total hip arthroplasty for suitable patients. Conclusions. Further observational research should be conducted to define the population of interest before future interventional studies are performed. Cite this article: C. Huxley, J. Achten, M. L. Costa, F. Griffiths, X. L. Griffin. A process evaluation of the WHiTE Two trial comparing total hip arthroplasty with and without dual mobility component in the treatment of displaced intracapsular fractures of the proximal femur: Can a trial investigating total hip arthroplasty for hip fracture be delivered in the NHS? Bone Joint Res 2016;5:444–452. DOI: 10.1302/2046-3758.510.BJR-2015-0008.R1


Aims

In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models.

Methods

The cell toxicity of different concentrations of EDTA dissolved in NS (EDTA-NS) was assessed by Cell Counting Kit-8 (CCK-8). Various concentrations of EDTA-NS irrigation solution were compared in three female Sprague-Dawley rat models: 1) a skin defect; 2) a bone exposed; and 3) a wound with an intra-articular implant. All three models were contaminated with Staphylococcus aureus or Escherichia coli. EDTA was dissolved at a concentration of 0 (as control), 0.1, 0.5, 1, 2, 5, 10, 50, and 100 mM in sterile NS. Samples were collected from the wounds and cultured. The bacterial culture-positive rate (colony formation) and infection rate (pus formation) of each treatment group were compared after irrigation and debridement.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 41 - 50
1 Jan 2021
Wong RMY Choy VMH Li J Li TK Chim YN Li MCM Cheng JCY Leung K Chow SK Cheung WH

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.

Methods

A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.


Bone & Joint Research
Vol. 1, Issue 6 | Pages 104 - 110
1 Jun 2012
Swinteck BJ Phan DL Jani J Owen JR Wayne JS Mounasamy V

Objectives. The use of two implants to manage concomitant ipsilateral femoral shaft and proximal femoral fractures has been indicated, but no studies address the relationship of dynamic hip screw (DHS) side plate screws and the intramedullary nail where failure might occur after union. This study compares different implant configurations in order to investigate bridging the gap between the distal DHS and tip of the intramedullary nail. Methods. A total of 29 left synthetic femora were tested in three groups: 1) gapped short nail (GSN); 2) unicortical short nail (USN), differing from GSN by the use of two unicortical bridging screws; and 3) bicortical long nail (BLN), with two angled bicortical and one unicortical bridging screws. With these findings, five matched-pairs of cadaveric femora were tested in two groups: 1) unicortical long nail (ULN), with a longer nail than USN and three bridging unicortical screws; and 2) BLN. Specimens were axially loaded to 22.7 kg (50 lb), and internally rotated 90°/sec until failure. Results. For synthetic femora, a difference was detected between GSN and BLN in energy to failure (p = 0.04) and torque at failure (p = 0.02), but not between USN and other groups for energy to failure (vs GSN, p = 0.71; vs BLN, p = 0.19) and torque at failure (vs GSN, p = 0.55; vs BLN, p = 0.15). For cadaveric femora, ULN and BLN performed similarly because of the improvement provided by the bridging screws. Conclusions. Our study shows that bicortical angled screws in the DHS side plate are superior to no screws at all in this model and loading scenario, and suggests that adding unicortical screws to a gapped construct is probably beneficial


Bone & Joint Research
Vol. 9, Issue 7 | Pages 429 - 439
1 Jul 2020
Tahir M Chaudhry EA Zaffar Z Anwar K Mamoon MAH Ahmad M Jamali AR Mehboob G

Aims

We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue.

Methods

This was a randomized control trial of 169 patients who required surgery for closed isolated distal radius fractures. The study was performed between March 2016 and April 2019 at a public sector level 1 trauma centre. General anaesthesia was used in 56 patients, Bier’s block in 58 patients, and WALANT in 55 patients. Data were collected on pre-, peri-, and postoperative parameters, clinical outcome, hospital costs, and patient satisfaction. One-way analysis of variance (ANOVA) was used with a p-value of 0.05 being significant.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 613 - 622
1 Sep 2020
Perucca Orfei C Lovati AB Lugano G Viganò M Bottagisio M D’Arrigo D Sansone V Setti S de Girolamo L

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Methods

A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 477 - 483
1 Aug 2020
Holweg P Herber V Ornig M Hohenberger G Donohue N Puchwein P Leithner A Seibert F

Aims

This study is a prospective, non-randomized trial for the treatment of fractures of the medial malleolus using lean, bioabsorbable, rare-earth element (REE)-free, magnesium (Mg)-based biodegradable screws in the adult skeleton.

Methods

A total of 20 patients with isolated, bimalleolar, or trimalleolar ankle fractures were recruited between July 2018 and October 2019. Fracture reduction was achieved through bioabsorbable Mg-based screws composed of pure Mg alloyed with zinc (Zn) and calcium (Ca) ( Mg-Zn0.45-Ca0.45, in wt.%; ZX00). Visual analogue scale (VAS) and the presence of complications (adverse events) during follow-up (12 weeks) were used to evaluate the clinical outcomes. The functional outcomes were analyzed through the range of motion (ROM) of the ankle joint and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Fracture reduction and gas formation were assessed using several plane radiographs.


Bone & Joint Research
Vol. 9, Issue 1 | Pages 1 - 14
1 Jan 2020
Stewart S Darwood A Masouros S Higgins C Ramasamy A

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 440 - 449
1 Jul 2020
Huang Z Li W Lee G Fang X Xing L Yang B Lin J Zhang W

Aims

The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.

Methods

A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 472 - 480
1 Oct 2019
Hjorthaug GA Søreide E Nordsletten L Madsen JE Reinholt FP Niratisairak S Dimmen S

Objectives

Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

Methods

A standardized closed tibia shaft fracture was induced and stabilized by reamed intramedullary nailing in 66 Wistar rats. A ‘parecoxib immediate’ (Pi) group received parecoxib (3.2 mg/kg bodyweight twice per day) on days 0, 1, and 2. A ‘parecoxib delayed’ (Pd) group received the same dose of parecoxib on days 3, 4, and 5. A control group received saline only. Fracture healing was evaluated by biomechanical tests, histomorphometry, and dual-energy x-ray absorptiometry (DXA) at four weeks.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 255 - 265
1 Jun 2019
Hernigou J Schuind F

Objectives

The aim of this study was to review the impact of smoking tobacco on the musculoskeletal system, and on bone fractures in particular.

Methods

English-language publications of human and animal studies categorizing subjects into smokers and nonsmokers were sourced from MEDLINE, The Cochrane Library, and SCOPUS. This review specifically focused on the risk, surgical treatment, and prevention of fracture complications in smokers.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 502 - 508
1 Oct 2019
Mao W Ni H Li L He Y Chen X Tang H Dong Y

Objectives

Different criteria for assessing the reduction quality of trochanteric fractures have been reported. The Baumgaertner reduction quality criteria (BRQC) are relatively common and the Chang reduction quality criteria (CRQC) are relatively new. The objectives of the current study were to compare the reliability of the BRQC and CRQC in predicting mechanical complications and to investigate the clinical implications of the CRQC.

Methods

A total of 168 patients were assessed in a retrospective observational study. Clinical information including age, sex, fracture side, American Society of Anesthesiologists (ASA) classification, tip-apex distance (TAD), fracture classification, reduction quality, blade position, BRQC, CRQC, bone quality, and the occurrence of mechanical complications were used in the statistical analysis.


Bone & Joint Research
Vol. 8, Issue 3 | Pages 107 - 117
1 Mar 2019
Lim ZXH Rai B Tan TC Ramruttun AK Hui JH Nurcombe V Teoh SH Cool SM

Objectives

Long bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done.

Methods

We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses.


Bone & Joint Research
Vol. 7, Issue 12 | Pages 639 - 649
1 Dec 2018
MacLeod AR Serrancoli G Fregly BJ Toms AD Gill HS

Objectives

Opening wedge high tibial osteotomy (HTO) is an established surgical procedure for the treatment of early-stage knee arthritis. Other than infection, the majority of complications are related to mechanical factors – in particular, stimulation of healing at the osteotomy site. This study used finite element (FE) analysis to investigate the effect of plate design and bridging span on interfragmentary movement (IFM) and the influence of fracture healing on plate stress and potential failure.

Materials and Methods

A 10° opening wedge HTO was created in a composite tibia. Imaging and strain gauge data were used to create and validate FE models. Models of an intact tibia and a tibia implanted with a custom HTO plate using two different bridging spans were validated against experimental data. Physiological muscle forces and different stages of osteotomy gap healing simulating up to six weeks postoperatively were then incorporated. Predictions of plate stress and IFM for the custom plate were compared against predictions for an industry standard plate (TomoFix).


Bone & Joint Research
Vol. 7, Issue 2 | Pages 139 - 147
1 Feb 2018
Takahara S Lee SY Iwakura T Oe K Fukui T Okumachi E Waki T Arakura M Sakai Y Nishida K Kuroda R Niikura T

Objectives

Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM.

Methods

Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 179 - 186
1 Feb 2018
Wu T Zhang J Wang B Sun Y Liu Y Li G

Objectives

As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing.

Materials and Methods

Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 423 - 432
1 Jul 2017
van der Stok J Hartholt KA Schoenmakers DAL Arts JJC

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.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 610 - 611
1 Oct 2017
Simpson AHRW


Bone & Joint Research
Vol. 7, Issue 6 | Pages 397 - 405
1 Jun 2018
Morcos MW Al-Jallad H Li J Farquharson C Millán JL Hamdy RC Murshed M

Objectives

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of fracture callus in mice.

Methods

Tibial fractures were created and then stabilized in control wild-type (WT) and Phospho1-/- mice (n = 16 for each group; mixed gender, each group carrying equal number of male and female mice) at eight weeks of age. Fractures were allowed to heal for four weeks and then the mice were euthanized and their tibias analyzed using radiographs, micro-CT (μCT), histology, histomorphometry and three-point bending tests.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 447 - 456
1 Jul 2018
Morgenstern M Vallejo A McNally MA Moriarty TF Ferguson JY Nijs S Metsemakers W

Objectives

As well as debridement and irrigation, soft-tissue coverage, and osseous stabilization, systemic antibiotic prophylaxis is considered the benchmark in the management of open fractures and considerably reduces the risk of subsequent fracture-related infections (FRI). The direct application of antibiotics in the surgical field (local antibiotics) has been used for decades as additional prophylaxis in open fractures, although definitive evidence confirming a beneficial effect is scarce. The purpose of the present study was to review the clinical evidence regarding the effect of prophylactic application of local antibiotics in open limb fractures.

Methods

A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Cohort studies investigating the effect of additional local antibiotic prophylaxis compared with systemic prophylaxis alone in the management of open fractures were included and the data were pooled in a meta-analysis.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 385 - 390
1 Jun 2017
Yang Y Lin S Wang B Gu W Li G

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.

Methods

We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Methods

Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 289 - 297
1 Apr 2018
Sanghani-Kerai A Osagie-Clouard L Blunn G Coathup M

Objectives

This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis.

Methods

Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 232 - 243
1 Mar 2018
Winkler T Sass FA Duda GN Schmidt-Bleek K

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.


Bone & Joint Research
Vol. 6, Issue 8 | Pages 489 - 498
1 Aug 2017
Mifuji K Ishikawa M Kamei N Tanaka R Arita K Mizuno H Asahara T Adachi N Ochi M

Objectives

The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing.

Methods

Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 124 - 130
1 Feb 2018
Coric D Bullard DE Patel VV Ryaby JT Atkinson BL He D Guyer RD

Objectives

Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures.

Methods

Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher’s exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 216 - 223
1 Apr 2017
Ang BFH Chen JY Yew AKS Chua SK Chou SM Chia SL Koh JSB Howe TS

Objectives

External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF).

Methods

A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness.


Bone & Joint Research
Vol. 5, Issue 3 | Pages 101 - 105
1 Mar 2016
Wang X Luo F Huang K Xie Z

Objectives

Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients.

Methods

A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 191 - 197
1 May 2016
Kienast B Kowald B Seide K Aljudaibi M Faschingbauer M Juergens C Gille J

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.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 358 - 365
1 Jun 2017
Sanghani-Kerai A Coathup M Samazideh S Kalia P Silvio LD Idowu B Blunn G

Objectives

Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration.

Methods

MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.


Bone & Joint Research
Vol. 6, Issue 4 | Pages 208 - 215
1 Apr 2017
Decambron A Manassero M Bensidhoum M Lecuelle B Logeart-Avramoglou D Petite H Viateau V

Objectives

To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects.

Materials and Methods

Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation.


Bone & Joint Research
Vol. 2, Issue 6 | Pages 102 - 111
1 Jun 2013
Patel RA Wilson RF Patel PA Palmer RM

Objectives

To review the systemic impact of smoking on bone healing as evidenced within the orthopaedic literature.

Methods

A protocol was established and studies were sourced from five electronic databases. Screening, data abstraction and quality assessment was conducted by two review authors. Prospective and retrospective clinical studies were included. The primary outcome measures were based on clinical and/or radiological indicators of bone healing. This review specifically focused on non-spinal orthopaedic studies.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 215 - 217
1 Jun 2016
Pijls BG Nelissen RGHH


Bone & Joint Research
Vol. 5, Issue 8 | Pages 320 - 327
1 Aug 2016
van IJsseldijk EA Valstar ER Stoel BC Nelissen RGHH Baka N van’t Klooster R Kaptein BL

Objectives

An important measure for the diagnosis and monitoring of knee osteoarthritis is the minimum joint space width (mJSW). This requires accurate alignment of the x-ray beam with the tibial plateau, which may not be accomplished in practice. We investigate the feasibility of a new mJSW measurement method from stereo radiographs using 3D statistical shape models (SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to variations in patient positioning and bone geometry.

Materials and Methods

A validation study was performed using five cadaver specimens. The actual mJSW was varied and images were acquired with variation in the cadaver positioning. For comparison purposes, the mJSW was also assessed from plain radiographs. To study the influence of SSM model accuracy, the 3D mJSW measurement was repeated with models from the actual bones, obtained from CT scans.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 178 - 184
1 May 2016
Dean BJF Jones LD Palmer AJR Macnair RD Brewer PE Jayadev C Wheelton AN Ball DEJ Nandra RS Aujla RS Sykes AE Carr AJ

Objectives

The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment.

Methods

A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 145 - 152
1 Apr 2016
Bodalia PN Balaji V Kaila R Wilson L

Objectives

We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis.

Methods

The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion.


Bone & Joint Research
Vol. 4, Issue 11 | Pages 176 - 180
1 Nov 2015
Mirghasemi SA Rashidinia S Sadeghi MS Talebizadeh M Rahimi N

Objectives

There are various pin-in-plaster methods for treating fractures of the distal radius. The purpose of this study is to introduce a modified technique of ‘pin in plaster’.

Methods

Fifty-four patients with fractures of the distal radius were followed for one year post-operatively. Patients were excluded if they had type B fractures according to AO classification, multiple injuries or pathological fractures, and were treated more than seven days after injury. Range of movement and functional results were evaluated at three and six months and one and two years post-operatively. Radiographic parameters including radial inclination, tilt, and height, were measured pre- and post-operatively.


Bone & Joint Research
Vol. 1, Issue 8 | Pages 167 - 173
1 Aug 2012
Jack CM Rajaratnam SS Khan HO Keast-Butler O Butler-Manuel PA Heatley FW

Objectives

To assess the effectiveness of a modified tibial tubercle osteotomy as a treatment for arthroscopically diagnosed chondromalacia patellae.

Methods

A total of 47 consecutive patients (51 knees) with arthroscopically proven chondromalacia, who had failed conservative management, underwent a modified Fulkerson tibial tubercle osteotomy. The mean age was 34.4 years (19.6 to 52.2). Pre-operatively, none of the patients exhibited signs of patellar maltracking or instability in association with their anterior knee pain. The minimum follow-up for the study was five years (mean 72.6 months (62 to 118)), with only one patient lost to follow-up.


Bone & Joint Research
Vol. 1, Issue 9 | Pages 205 - 209
1 Sep 2012
Atrey A Morison Z Tosounidis T Tunggal J Waddell JP

We systematically reviewed the published literature on the complications of closing wedge high tibial osteotomy for the treatment of unicompartmental osteoarthritis of the knee. Publications were identified using the Cochrane Library, MEDLINE, EMBASE and CINAHL databases up to February 2012. We assessed randomised (RCTs), controlled group clinical (CCTs) trials, case series in publications associated with closing wedge osteotomy of the tibia in patients with osteoarthritis of the knee and finally a Cochrane review. Many of these trials included comparative studies (opening wedge versus closing wedge) and there was heterogeneity in the studies that prevented pooling of the results.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 123 - 129
1 Apr 2014
Perry DC Griffin XL Parsons N Costa ML

The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. ‘Trauma’ amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research.

Cite this article: Bone Joint Res 2014;3:123–9.


Bone & Joint Research
Vol. 1, Issue 7 | Pages 152 - 157
1 Jul 2012
Hamilton DF Gatherer D Jenkins PJ Maclean JGB Hutchison JD Nutton RW Simpson AHRW

Objectives

To evaluate the neck strength of school-aged rugby players, and to define the relationship with proxy physical measures with a view to predicting neck strength.

Methods

Cross-sectional cohort study involving 382 rugby playing schoolchildren at three Scottish schools (all male, aged between 12 and 18 years). Outcome measures included maximal isometric neck extension, weight, height, grip strength, cervical range of movement and neck circumference.


Bone & Joint Research
Vol. 2, Issue 6 | Pages 112 - 115
1 Jun 2013
Ismail HD Phedy P Kholinne E Kusnadi Y Sandhow L Merlina M

Objectives

Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest.

Methods

We enrolled five patients with neglected atrophic nonunions of long bones confirmed by clinical examinations and plain radiographs into this study. As much as 10 ml bone marrow aspirate was obtained from both the nonunion site and the iliac crest and cultured for three weeks. Cell numbers were counted using a haemocytometer and vitality of the cells was determined by trypan blue staining. The cells were confirmed as MSCs by evaluating their expression marker (CD 105, CD 73, HLA-DR, CD 34, CD 45, CD 14, and CD 19). Cells number and viability were compared between the nonunion and iliac creat sites.


Bone & Joint Research
Vol. 2, Issue 3 | Pages 51 - 57
1 Mar 2013
Sullivan MP Torres SJ Mehta S Ahn J

Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 272 - 280
1 Oct 2012
De Mattos CBR Binitie O Dormans JP

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated.


Bone & Joint Research
Vol. 1, Issue 1 | Pages 1 - 7
1 Jan 2012
Rosenberg N Rosenberg O

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.

Methods

Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining.