Jacobus J. Arts

Clinical Applications of S53P4 Bioactive Glass in Bone Healing and Osteomyelitic Treatment: A Literature Review

Nowadays, S53P4 bioactive glass is indicated as a bone graft substitute in various clinical applications. This review provides an overview of the current published clinical results on indications such as craniofacial procedures, grafting of benign bone tumour defects, instrumental spondylodesis, and the treatment of osteomyelitis. Given the reported results that are based on examinations, such as clinical examinations by the surgeons, radiographs, CT, and MRI images, S53P4 bioactive glass may be beneficial in the various reported applications. Especially in craniofacial reconstructions like mastoid obliteration and orbital floor reconstructions, in grafting bone tumour defects, and in the treatment of osteomyelitis very promising results are obtained. Randomized clinical trials need to be performed in order to determine whether bioactive glass would be able to replace the current golden standard of autologous bone usage or with the use of antibiotic containing PMMA beads (in the case of osteomyelitis).

Clinical Application of Antimicrobial Bone Graft Substitute in Osteomyelitis Treatment: A Systematic Review of Different Bone Graft Substitutes Available in Clinical Treatment of Osteomyelitis

Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn.

How to prepare a systematic review of economic evaluations for informing evidence-based healthcare decisions: a five-step approach (part 1/3)

ABSTRACT Introduction: Systematic reviews of economic evaluations are useful for synthesizing economic evidence about health interventions and for informing evidence-based decisions. Areas covered: As there is no detailed description of the methods for performing a systematic review of economic evidence, this paper aims to provide an overview of state-of-the-art methodology. This is laid out in a 5-step approach, as follows: step 1) initiating a systematic review; step 2) identifying (full) economic evaluations; step 3) data extraction, risk of bias and transferability assessment; step 4) reporting results; step 5) discussion and interpretation of findings. Expert commentary: The paper aims to help inexperienced reviewers and clinical practice guideline developers, but also to be a resource for experts in the field who want to check on current methodological developments.

Bone reaction to a biomimetic third-generation hydroxyapatite coating and new surface treatment for the Symax hip stem

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface. Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer. The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.

A rabbit osteomyelitis model for the longitudinal assessment of early post-operative implant infections

BackgroundImplant infection is one of the most severe complications within the field of orthopaedic surgery, associated with an enormous burden for the healthcare system. During the last decades, attempts have been made to lower the incidence of implant-related infections. In the case of cemented prostheses, the use of antibiotic-containing bone cement can be effective. However, in the case of non-cemented prostheses, osteosynthesis and spinal surgery, local antibacterial prophylaxis is not a standard procedure. For the development of implant coatings with antibacterial properties, there is a need for a reliable animal model to evaluate the preventive capacity of such coatings during a specific period of time. Existing animal models generally present a limited follow-up, with a limited number of outcome parameters and relatively large animal numbers in multiple groups.MethodsTo represent an early post-operative implant infection, we established an acute tibial intramedullary nail infection model in rabbits by contamination of the tibial nail with 3.8 × 105 colony forming units of Staphylococcus aureus. Clinical, haematological and radiological parameters for infection were weekly assessed during a 6-week follow-up with post-mortem bacteriological and histological analyses.ResultsS. aureus implant infection was confirmed by the above parameters. A saline control group did not develop osteomyelitis. By combining the clinical, haematological, radiological, bacteriological and histological data collected during the experimental follow-up, we were able to differentiate between the control and the infected condition and assess the severity of the infection at sequential timepoints in a parameter-dependent fashion.ConclusionWe herein present an acute early post-operative rabbit implant infection model which, in contrast to previously published models, combines improved in-time insight into the development of an implant osteomyelitis with a relatively low amount of animals.

Large animal models in fusionless scoliosis correction research: a literature review

BACKGROUND CONTEXT Numerous prenatal, systemic, or local procedures have been described that have created an experimental scoliosis within different animal species. Compression-based fusionless scoliosis correction devices have been used to induce scoliosis (inverse approach) as an indication for their potential corrective efficacy in large animals. Deformities that most closely approximate the three-dimensional nature of an idiopathic-like scoliosis have been created in large animals using a posterior spinal tether. Fusionless scoliosis correction devices have subsequently been tested in these models. PURPOSE To provide an overview of large animal models used for preclinical testing of fusionless scoliosis correction devices and to describe recent advances in the creation of an idiopathic-like scoliosis large animal model. STUDY DESIGN Literature review of large animal models in fusionless scoliosis correction research. METHODS MEDLINE electronic database was searched for studies in which large animal models for spinal or vertebral growth modulation or the creation of an experimental scoliosis were described. The literature search was limited to articles written in the English language. RESULTS The pig appears to be the most suitable animal species for preclinical testing of fusionless scoliosis correction devices because of its large growth potential and the possibility for early weaning. With the inverse approach, it is difficult to gain insight into the possible corrective efficacy of the tested device, and therefore, a two-step approach is preferred. Using a posterior spinal tether, persistent spinal deformities are attained when the deformity has approximately doubled in comparison to the postoperative measure in a time span of approximately 12 weeks. Sufficient tether midline offset is required to render rib procedures unnecessary. CONCLUSIONS An idiopathic-like scoliosis animal model can be created using a posterior spinal tether in a fully reversible procedure. Experimental results will need to be reproduced to establish a standard idiopathic-like scoliosis large animal model.

Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections – A Multinational Study

Osteomyelitis is an infectious process in bone that occasionally leads to bone destruction. Traditionally, the surgical treatment procedure is performed in combination with systemic and local antibiotics as a two-stage procedure that uses autograft or allograft bone for filling of the cavitary defect. Bioactive glass (BAG-S53P4) is a bone substitute with proven antibacterial and bone bonding properties.One hundred and sixteen patients who had verified chronic osteomyelitis was treated using BAG-S53P4 as part of the treatment. Most of the patients had previously undergone numerous procedures, sometimes for decades. A register of patient data obtained from 11 centers from Finland, Italy, the Netherlands, Germany, Azerbaijan and Poland was set-up and continuously maintained at Helsinki University Central Hospital.The location of the osteomyelitis was mainly in the tibia followed by the femur and then the calcaneus. The median age of the patients was 48 years (15-87). The patients were either treated according to a one-stage procedure without local antibiotics (85 %) or by a two-stage procedure using antibiotic beads in the first procedure (15 %). The minimum follow-up was 1 year (12-95 months, median 31).The cure rate was 104/116, the total success rate 90 % and most of the patients showed a rapid recovery.The study shows that (BAG-S53P4) can be used in a one-stage procedure in treatment of osteomyelitis with excellent results.

The Longitudinal Assessment of Osteomyelitis Development by Molecular Imaging in a Rabbit Model

Introduction. Osteomyelitis is a severe orthopaedic complication which is difficult to diagnose and treat. Previous experimental studies mainly focussed on evaluating osteomyelitis in the presence of an implant or used a sclerosing agent to promote infection onset. In contrast, we focused on the longitudinal assessment of a nonimplant related osteomyelitis. Methods. An intramedullary tibial infection with S. aureus was established in NZW rabbits. Clinical and haematological infection status was evaluated weekly, combined with X-ray radiographs, biweekly injections of calcium binding fluorophores, and postmortem micro-CT. The development of the infection was assessed by micro-PET at consecutive time points using 18F-FDG as an infection tracer. Results. The intramedullary contamination of the rabbit tibia resulted in an osteomyelitis. Haematological parameters confirmed infection in mainly the first postoperative weeks (CRP at the first 5 postoperative weeks, leucocyte differentiation at the second and sixth postoperative weeks, and ESR on the second postoperative week only), while micro-PET was able to detect the infection from the first post-operative week onward until the end of the study. Conclusions. This study shows that osteomyelitis in the rabbit can be induced without use of an implant or sclerosing agent. The sequential follow-up indicates that the diagnostic value of each infection parameter is time point dependant. Furthermore, from all parameters used, the diagnostic value of  18F-FDG micro-PET is the most versatile to assess the presence of an orthopaedic infection in this model.

Fracture repair in the distal radius in postmenopausal women:a follow-up 2 years postfracture using HRpQCT

Fracture healing is characterized by an intense increase in modeling and remodeling of bone, which allows removal of the cast after a stable distal radius fracture within 3 to 5 weeks. However, at that time, bone strength has not recovered yet. We studied the changes in bone mineral density (BMD), microarchitecture, and bone stiffness after a distal radius fracture during a 2‐year follow‐up in comparison to the contralateral side and the association between the 2‐year stiffness and baseline BMD, microarchitecture, and early changes in these parameters. The fractured side of 14 postmenopausal women (mean age 64 ± 8 years) with a conservatively treated distal radius fracture was scanned by high‐resolution peripheral quantitative computed tomography (HRpQCT) at 1 to 2, 3 to 4, 6 to 8, and 12 weeks and 2 years postfracture. The same region contralaterally was scanned as well at the 2‐year visit. BMD, microarchitecture, and stiffness parameters were determined and the fracture side was compared with the contralateral side using a linear mixed‐effect model. Spearmans correlation was used to correlate the 2‐year bone stiffness with baseline BMD, microarchitecture, and early 3‐month changes in these parameters. Two years postfracture, cortical and trabecular thickness and torsional and bending stiffness were significantly higher at the fractured side compared with the nonfractured side (21%, 55%, 31%, and 29%, respectively, p < 0.05), whereas BMD was similar. Two‐year torsional and bending stiffness correlated significantly with baseline BMD and cortical perimeter (|rho| ≥ 0.63, p < 0.016) but not with early changes in bone parameters. Using HRpQCT, this study illustrates that fracture healing is not completed by the time the cast is removed. We showed that from 6 weeks to 2 years postfracture, large changes occur in BMD, microarchitecture, and biomechanical parameters at the fractured side, which were fully recovered after 2 years in comparison to the nonfractured contralateral side. Interestingly, higher 2‐year torsional and bending stiffness were associated with lower BMD and higher cortical perimeter at baseline.

Improving peri-prosthetic bone adaptation around cementless hip stems: A clinical and finite element study

This study assessed whether the Symax™ implant, a modification of the Omnifit(®) stem (in terms of shape, proximal coating and distal surface treatment), would yield improved bone remodelling in a clinical DEXA study, and if these results could be predicted in a finite element (FE) simulation study. In a randomized clinical trial, 2 year DEXA measurements between the uncemented Symax™ and Omnifit(®) stem (both n=25) showed bone mineral density (BMD) loss in Gruen zone 7 of 14% and 20%, respectively (p<0.05). In contrast, the FE models predicted a 28% (Symax™) and 26% (Omnifit(®)) bone loss. When the distal treatment to the Symax™ was not modelled in the simulation, bone loss of 35% was predicted, suggesting the benefit of this surface treatment for proximal bone maintenance. The theoretical concept for enhanced proximal bone loading by the Symax™, and the predicted remodelling pattern were confirmed by DEXA-results, but there was no quantitative match between clinical and FE findings. This was due to a simulation based on incomplete assumptions concerning the yet unknown biological and mechanical effects of the new coating and surface treatment. Study listed under ClinicalTrials.gov with number NCT01695213.