The Effect of RANKL/OPG Balance on Reducing Implant Complications

Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion. The effects of pro-inflammatory factors play a significant role in initiating and maintaining osteoclastogenesis that results in bone resorption by osteoclasts. This is because there is a disruption of the relative ratio between Receptor Activator of Nuclear Factor κB-Ligand (RANKL) and osteoprotegerin (OPG), which is central to modulating bone repair and remodelling. This review aims to provide a background to the bone remodelling process, the bone repair cascade post-implantation, and the associated complications. Furthermore, current clinical solutions that can influence bone formation via either internal or extrinsic mechanisms will be described. These efficacious treatments for osteolysis via targeting the RANKL/OPG ratio may be crucial to reducing the incidence of related implant failures in the future

Docking site interventions following bone transport using external fixation: a systematic review of the literature

Purpose Although bone transport is a well-recognised technique to address segmental bone defects, optimal management of docking sites is not absolutely determined. Some surgeons routinely intervene in all cases, and others prefer to observe and intervene only if spontaneous union does not occur. Primary aim of the study was to compare rates of docking site union between patients who underwent routine docking site intervention and those who did not. Methods A systematic literature review using the keywords “bone transport”, “docking”, “tibia”, and “femur” was performed in PubMed using PRISMA guidelines. Studies published in English from January 2000 to August 2022 were included and assessed independently by two reviewers. Pooled analysis was undertaken dividing patients into two groups: those managed by routine intervention and those initially observed. Results Twenty-three clinical studies met the eligibility criteria for pooled analysis, including 1153 patients, 407 in the routine intervention and 746 in the observed group. The rate of union after initial treatment was 90% in the routine intervention group and 66% in the observed group (p < 0.0001). Overall union rates at the end of treatment were similar at 99% in both groups. Patients in the observed group required an average of 2.2 procedures to achieve union overall compared with 3.8 in the routine intervention group. Time in frame was similar between groups. Conclusion Based on the current literature, routine docking site interventions cannot be recommended, since this may lead to unnecessary interventions in two thirds of patients. Timely selective intervention in those at high risk or after a defined period of observation would appear to be a logical approach

Do patients with diabetes mellitus and polytrauma continue to have worse outcomes?

The management of patients with multiple injuries remains challenging. Patients presenting with comorbidities, such as diabetes mellitus, may have additional unpredictable outcomes with increased mortality. Therefore, we aim to investigate the impact of major trauma centres in the UK on the outcomes of polytrauma patients with diabetes. The Trauma Audit and Research Network was used to identify polytrauma patients presenting to centres in England and Wales between 2012 and 2019. In total, 32,345 patients were thereby included and divided into three groups: 2271 with diabetes, 16,319 with comorbidities other than diabetes and 13,755 who had no comorbidities. Despite an overall increase in diabetic prevalence compared to previously published data, mortality was reduced in all groups, but diabetic patient mortality remained higher than in the other groups. Interestingly, increasing Injury Severity Score (ISS) and age were associated with increasing mortality, whereas the presence of diabetes, even when taking into consideration age, ISS and Glasgow Coma Score, led to an increase in the prediction of mortality with an odds ratio of 1.36 (p < 0.0001). The prevalence of diabetes mellitus in polytrauma patients has increased, and diabetes remains an independent risk factor for mortality following polytrauma

Unstable pelvic fractures in women: implications on obstetric outcome

Purpose Obstetric outcomes in women following pelvic injuries requiring surgical fixation is not thoroughly known. We aimed to evaluate if radiographic measurements (RMs) can be used to provide information on delivery methods outcome after these injuries, and to evaluate if metal work removal is required prior to delivery. Method A retrospective study in a level 1 trauma centre of female patients with pelvic fractures treated operatively, aged 16–45 at the time of injury. Participants completed a questionnaire regarding their obstetric history. RM evaluating pelvic symmetry, displacement, and pelvimetry were conducted on postoperative radiographs and CT scans. Patients who gave birth after the injury were divided to two groups according to the delivery method: vaginal delivery (VD) and caesarean section (CS). These two groups RM were compared. Results Forty-four patients were included, comparison of the RM of patients who delivered by CS (9) and patients who had only VD (11) showed no significant difference between the groups. Two patients underwent a trial of VD who subsequently underwent urgent CS due to prolonged labour, their RM were below the average and their pelvimetry measurements were above the cut-off for CS recommendation. Eleven patients had uncomplicated VD, all had retained sacroiliac screws at the time of delivery and one patient had an anterior pubic plate. Conclusion Postoperative RM did not show an effect on delivery method of women after pelvic fracture fixation. A relatively high number of patients who underwent normal vaginal delivery had retained sacroiliac screws. These findings can form the foundation for larger cohort studies

Physiologically engineered porous titanium/brushite scaffolds for critical-size bone defects: A design and manufacturing study

Repairing critical-size bone defects still represents a critical clinical challenge in the field of trauma surgery. This study focuses on a physiological design and manufacturing of porous composite scaffold (titanium Ti with 10 % mole iron doped brushite DCPD-Fe3+) which can mimic the biomechanical properties of natural cortical bone, specifically for the purpose of repairing critical-size defects. To achieve this, the principle of design of experiments (DOE) was applied for investigating the impact of sintering temperature, mineral ratio, and volume fraction of porosity on the mechanical properties of the fabricated scaffolds. The fabricated scaffolds had open porosity up to 60 %, with pore size approximately between 100 μm and 850 μm. The stiffness of the porous composite scaffolds varied between 3.30 GPa and 20.50 GPa, while the compressive strength ranged from approximately 130 MPa–165 MPa at sintering temperatures equal to or exceeding 1000 °C. Scaffolds with higher porosity and mineral content demonstrated lower stiffness values, resembling natural bone. Numerical simulation was employed by Ansys Workbench to investigate the stress and strain distribution of a critical size defect in mid-shaft femur which was designed to be replaced with the fabricated scaffold. The fabricated scaffolds showed flexible biomechanical behaviour at the bone/scaffold interface, generating lower stress levels and indicating a better match with the femoral shaft stiffness. The experimental and numerical findings demonstrated promising applications for manufacturing a patient-specific bone scaffold for critical and potentially large defects for reducing stress shielding and minimizing non-union risk

Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

[Abstract] Background: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. Materials and Methods: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). Results: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. Conclusions: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy

Retrograde intramedullary nailing or locked plating for stabilisation of distal femoral fractures? A comparative study of 193 patients

Purpose The aim of this study was to evaluate the results of distal femoral fracture fixation of two different methods, lateral locking plate (LP) or an Intra-medullary nail (IMN), in patients managed in our institution. More specifically, to assess: (a) if there was a difference in functional outcomes between the LP and IMN groups; (b) whether the rate of complications was different between the two groups. Methods Between January 2009 and December 2018 adult patients with distal femoral fractures managed in our unit with either LP or IMN for extra and intra-articular fractures were eligible to participate. Demographic details, fracture type, procedures performed, time to union, complications and functional scores (Oxford Knee Score) were recorded and analysed. The mean follow up was 4 years (12–120 months). Results Out of 193 patients who met the inclusion criteria, 93 received an IMN whereas 100 patients were treated with LP. Mean age was 64.2 (18–99) and 70.1 (18–100) for the IMN and LP groups respectively. Overall, the two groups had similar demographics and there was no significant difference in the type of fractures sustained (p > 0.05). The Oxford Knee Score was highest for patients fixed with LP, mean 37.3 (6–48, SD 7.3) versus 28.4 (3–48, SD 14.4), (p =  < 0.02) compared to the IMN group. In terms of complications, the rate of non-union was higher in the LP group 8.6% versus 4% in those patients treated with an IMN, p value < 0.01. Conclusion While the rate of non-union was higher in the LP group and the functional results were superior in the plating group

Fracture-related outcome study for operatively treated tibia shaft fractures (F.R.O.S.T.): registry rationale and design

Background: Tibial shaft fractures (TSFs) are among the most common long bone injuries often resulting from high-energy trauma. To date, musculoskeletal complications such as fracture-related infection (FRI) and compromised fracture healing following fracture fixation of these injuries are still prevalent. The relatively high complication rates prove that, despite advances in modern fracture care, the management of TSFs remains a challenge even in the hands of experienced surgeons. Therefore, the Fracture-Related Outcome Study for operatively treated Tibia shaft fractures (F.R.O.S.T.) aims at creating a registry that enables data mining to gather detailed information to support future clinical decision-making regarding the management of TSF’s. Methods: This prospective, international, multicenter, observational registry for TSFs was recently developed. Recruitment started in 2019 and is planned to take 36 months, seeking to enroll a minimum of 1000 patients. The study protocol does not influence the clinical decision-making procedure, implant choice, or surgical/imaging techniques; these are being performed as per local hospital standard of care. Data collected in this registry include injury specifics, treatment details, clinical outcomes (e.g., FRI), patient-reported outcomes, and procedure- or implant-related adverse events. The minimum follow up is 12 months. Discussion: Although over the past decades, multiple high-quality studies have addressed individual research questions related to the outcome of TSFs, knowledge gaps remain. The scarcity of data calls for an international high-quality, population-based registry. Creating such a database could optimize strategies intended to prevent severe musculoskeletal complications. The main purpose of the F.R.O.S.T registry is to evaluate the association between different treatment strategies and patient outcomes. It will address not only operative techniques and implant materials but also perioperative preventive measures. For the first time, data concerning systemic perioperative antibiotic prophylaxis, the influence of local antimicrobials, and timing of soft-tissue coverage will be collected at an international level and correlated with standardized outcome measures in a large prospective, multicenter, observational registry for global accessibility. Trial registration: ClinicalTrials.gov: NCT03598530