Infectious Bone Disease Research Articles

Efficacy Analysis of Anti-Tuberculosis Chemotherapy Combined with Arthroplasty or Joint Replacement for Tuberculous of the Elbow Joint: A Retrospective Study of 40 Patients.

Tuberculous arthritis of the elbow joint (TAEJ) is a relatively rare infectious bone and joint disease. Misdiagnosed owing to inconspicuous early symptoms, often the elbow joint has suffered serious damage at the time of treatment. This study retrospectively investigated the clinical manifestations, population characteristics, clinical diagnosis, surgical treatment, and functional recovery of elbow joint tuberculosis (TB). A retrospective study of 40 patients was conducted. These patients were diagnosed with tuberculous arthritis of the elbow from June 2007 to August 2021 and were diagnosed with TAEJ by fine-needle aspiration biopsy or biopsy of surgically excised lesions. All patients underwent surgery after taking regular anti-TB drugs and chemotherapy for 2 weeks. Visual analogue scale score, Mayo elbow performance score, and hospital for special surgery assessment scale score were used to evaluate postoperative functional recovery. Imaging tests were used to evaluate patients' postoperative recovery. Forty patients were followed up for an average of 12.5 ±0.5 months. Erythrocyte sedimentation rate and C-reactive protein values returned to normal after anti-TB drug chemotherapy combined with surgical removal of infected lesion tissue; only one patient relapsed 16 months after surgery. Tuberculous arthritis of the elbow joint should be diagnosed in an early stage based on clinical manifestations, laboratory tests, and histopathological examinations. Complete surgical removal of the lesions should be performed after chemotherapy with anti-TB drugs for 2 weeks. The corresponding operation should be selected according to the damage in the elbow joint.

The involvement of endogenous melatonin in LPS-induced M1-like macrophages and its underlying synthesis mechanism regulated by IRF3

Melatonin (MLT) has been shown to induce polarization of macrophages towards M2-like phenotype and inhibit polarization of macrophages towards M1-like phenotype through exogenous administration, which affects the development of many macrophage polarization-related diseases, such as infectious diseases, cardiovascular diseases, bone diseases, and tumors. However, whether endogenous melatonin has similar influences on macrophage polarization as exogenous melatonin is still under investigation. This study revealed that the process of lipopolysaccharide (LPS) inducing macrophages to polarize towards M1-like phenotype was accompanied by an increase in endogenous MLT secretion. To explore the role of increased endogenous MLT in the polarization process of macrophages, whether similar to the function of exogenous MLT in inhibiting polarization of macrophages towards M1-like phenotype, we established LPS-induced MLT deficiency models in vitro to investigate the effects of endogenous MLT on the secretion of cytokines, co-stimulatory molecules, ROS, and phagocytic function in LPS-induced M1-like macrophages. Additionally, we aimed to elucidate the mechanism by which LPS affects the secretion of endogenous MLT by macrophages. Our results confirm that LPS induces transcription of Aanat through the TLR4/TRIF pathway, consequently facilitating the secretion of MLT by macrophages. In this way, IRF3 is the main transcription factor that regulates Aanat transcription. Endogenous MLT plays a role in inhibiting the polarization of macrophages towards M1 phenotype and delaying cell apoptosis during LPS-induced polarization towards M1 phenotype. This phenomenon may be a form of self-protection that occurs when macrophages engulf pathogens while avoiding oxidative stress and apoptosis caused by LPS. This conclusion clarifies the role of endogenous MLT in the clearance of pathogens by macrophages, providing a theoretical basis for understanding its role in innate immunity.

A Sr@Ag-based spatiotemporal and step-release scaffold against chronic osteomyelitis, fabricated by coaxial 3D-printing

Chronic osteomyelitis (OM) represents a severe and persistent infectious bone disease. Effective treatment requires controlled anti-inflammatory releases and bone regeneration across disease phases. A Sr@Ag-based scaffold was successfully printed, featuring micron-scale coaxial fibers containing Ag-doped hydroxyapatite (HA) in the outer layer of PLLA and Sr-doped HA in the inner layer of PLLA, facilitating the spatiotemporal and sequential release of Ag and Sr ions during OM treatment. Most antibacterial agent (Ag) was released during the first 20 days, followed by a slow-release plateau over the next 40 days in phosphate-buffered saline solution (PBS). Meanwhile, the pro-angiogenic agent (Sr) was released in minimal amounts during the initial 20 days, followed by a rapid and considerable release in the following 40 days. The coaxial design effectively inhibited the growth of Staphylococcus aureus and Escherichia coli while preserving the viability of bone cells. The ion-based scaffold exhibited broad-spectrum antibacterial effects and enhanced bone-regenerating gene expression in a complex air-bacteria environment. The Sr@Ag-based coaxial scaffold demonstrated effective antibacterial activity during the early stage and exhibited excellent non-toxic bone regeneration results during the middle and late stages in vivo. This work offered a promising treatment strategy through sequential anti-inflammatory and pro-osteogenic effects for infectious bone-defect diseases.

A Janus-ROS Healing System Promoting Infectious Bone Regeneration via Sono-Epigenetic Modulation.

Elimination of bacterial infections and simultaneously promoting osteogenic differentiation are highly required for infectious bone diseases. Massive reactive oxygen species (ROS) can damage cells, while low ROS concentrations as a molecular signal can regulate cellular fate. In this study, a Janus-ROS healing system is developed for infectious bone regeneration. An alendronate (ALN)-mediated defective metal-organic framework (MOF) sonosensitizer is prepared, which can effectively clear Methicillin-resistant Staphylococcus aureus (MRSA) infections and promote osteogenic differentiation under differential ultrasonic irradiation. In the presence of zirconium-phosphate coordination, the ALN-mediated porphyrin-based MOF (HN25) with a proper defect has great sonodynamic antibacterial efficiency (98.97%, 15min) and bone-targeting ability. Notably, under low-power ultrasound irradiation, HN25 can increase the chromatin accessibility of ossification-related genes and FOXO1 to promote bone repair through low ROS concentrations. Animal models of paravertebral infection, fracture with infection, and osteomyelitis demonstrate that HN25 successfully realizes the targeted and potent repair of various infectious bone tissues through rapid MRSA elimination, inhibiting osteoclast activity and promoting bone regeneration. The results show that high catalytic efficiency and bioactive MOF can be constructed using pharmaceutical-mediated defect engineering. The Janus-ROS treatment is also a promising therapeutic mode for infectious tissue regeneration.

La diagnosi differenziale del dolore osseo in età pediatrica: quando preoccuparsi

Bone pain is a common cause of admission to the Paediatric Emergency Department. Although in most cases it is associated with benign processes, this symptom should be investigated thoroughly when anamnestic and clinical features suggest the possible presence of an underlying malignant process. This article describes the case of an adolescent presenting with persistent musculoskeletal pain, initially treated as an infectious bone disease that later turned out to be a malignant neoplasm. Based on clinical, laboratory and imaging data the differential diagnosis of paediatric bone pain can sometimes be challenging and includes nonneoplastic diseases, benign bone tumours and malignant bone tumours. Moreover, this article indicates the medical history data to be investigated, the signs and symptoms to be evaluated and the laboratory and imaging investigations to be performed in a paediatric patient with bone pain. In addition, the epidemiological, clinical and radiographic characteristics of the most frequent causes of paediatric bone pain are summarized in a final table.

Obtaining a bone biopsy in acute hematogenous osteomyelitis using a new surgical instrument: A technical note

Acute hematogenous osteomyelitis is an infectious and inflammatory tubular bone disease involving the bone marrow. The final diagnosis is made based on a morphological study obtained from a bone biopsy. We have developed and patented a surgical instrument (Patent RU No 176629) for one-stage osteoperforation and trepan biopsy. Bone biopsy specimens obtained have been tested for their suitability for morphological examination, namely light and electron microscopy. It has a diagnostic and therapeutic function. This report aimed to describe a new bone biopsy tool that allows obtaining specimens suitable for morphological studies.

Surface Multifunctionalization of Inert Ceramic Implants by Calcium Phosphate Biomimetic Coating Doped with Nanoparticles Encapsulating Antibiotics.

Aseptic loosening and periprosthetic infections are complications that can occur at the interface between inert ceramic implants and natural body tissues. Therefore, the need for novel materials with antibacterial properties to prevent implant-related infection is evident. This study proposes multifunctionalizing the inert ceramic implant surface by biomimetic calcium phosphate (CaP) coating decorated with antibiotic-loaded nanoparticles for bioactivity enhancement and antibacterial effect. This study aimed to coat zirconium dioxide (ZrO2) substrates with a bioactive CaP-layer containing drug-loaded degradable polymer nanoparticles (NPs). The NPs were loaded with two antibiotics, gentamicin or bacitracin. The immobilization of NPs happened by two deposition methods: coprecipitation and drop-casting. X-ray diffraction (XRD), scanning electron microscopy (SEM), and cross-section analyses were used to characterize the coatings. MG-63 osteoblast-like cells and human mesenchymal stem cells (hMSC) were chosen for in vitro tests. Antibacterial activity was assessed with S. aureus and E. coli. The coprecipitation method allowed for a favorable homogeneous distribution of the NPs within the CaP coating. The CaP coating was constituted of hydroxyapatite and octacalcium phosphate; its thickness was 3.8 ± 1 μm with cavities of around 1 μm suitable for hosting NPs with a size of 200 nm. Antibiotics were released from the coatings in a controlled manner for 1 month. The cell culture study has confirmed the excellent behavior of the coprecipitated coating, showing cytocompatibility and a homogeneous distribution of the cells on the coated surfaces. The increase in alkaline phosphatase activity showed osteogenic differentiation. The materials were found to inhibit the growth of bacteria. Newly developed coatings with antibacterial and bioactive properties are promising candidates to prevent peri-implant infectious bone diseases.

Blood parasites and acute osteomyelitis in a non-avian dinosaur (Sauropoda, Titanosauria) from the Upper Cretaceous Adamantina Formation, Bauru Basin, Southeast Brazil

This research documents for the first time the detailed histological description of severe bone inflammation and the exceptional preservation of soft-bodied parasitical microorganisms inside the vascular canals of a non-avian dinosaur. The results bring new insights into the fields of parasitology, pathology, and histology in the fossil record. A senile titanosaur from the Upper Cretaceous of Southeast Brazil presented acute osteomyelitis, identified by the presence of a highly reactive periosteum with a filigree pattern, and localized dome-like cortical tissue inflammation connecting the former to the medulla. Furthermore, tens of parasites were identified throughout the specimen's vascular canals. Novel histological insights resulted from the developmental description of an aggressive case of osteomyelitis. The lesions were either caused or facilitated by the parasitic infestation. This may be the earliest occurrence of infectious bone disease associated with parasites, adding new information to the complex biogeographic and evolutionary history of parasitic ailments.

Consensus statement on the assessment of comorbidities in people living with HIV in Romania.

The life expectancy of HIV-infected patients has been increased by highly effective therapies. People living with HIV (PLWH) in Romania are exposed to age-related comorbidities occurring earlier than in uninfected individuals. Multidisciplinary care is required to maintain the general health and quality of life in these patients. Currently, the communication among different specialties needs to be enhanced and formalized. A panel consisting of 8 Romanian experts in infectious diseases, cardio-metabolic, bone, and kidney diseases and psychology met in May 2019 in Bucharest Romania to discuss the need to evaluate and monitor the most prevalent comorbidities in PLWH. The meeting resulted in practical guidance on the management of several non-infectious associated diseases. The algorithms were endorsed by the Society for Infectious Diseases and HIV/AIDS, Romania. The consensus statement offers practical guidance on how to assess and monitor associated diseases in adult PLWH. The recommendations are grouped for each cluster of comorbidities and are based on international guidelines and clinical experience, including landmarks for referral of PLWH to cardiology, endocrinology, nephrology specialist or clinical psychologist for additional investigations and adequate treatment. Specific indications for diagnosis or treatment were beyond the scope of this consensus. Screening for associated diseases and adequate management are required to maintain the overall health status of PLWH. When implemented in clinical practice, the recommended algorithms should be used in addition to diagnosis and treatment guidelines and protocols. The infectious diseases specialist plays a key role in coordinating the overall treatment strategy and working within the multidisciplinary team.

Ciprofloxacin‐Loaded Ceramic/Polymer Composite Coatings on Ti with Improved Antibacterial and Corrosion Resistance Properties for Orthopedic Applications

AbstractPast few decades witnessed the upcoming of osteomyelitis which is a challenging infectious bone disease. Complications related to this infection is encountered by local drug delivery via orthopedic surgery. In this work, TiO2‐SiO2 based bioceramics coatings were fabricated on Ti alloy by anodization method using sulphuric acid and Sodium silicofluoride (SSF) as an electrolyte. Plasma polymerized ethylenediamine (PPEDA) thin film deposited on composites by inductively coupled plasma chemical vapor deposition and followed by ciprofloxacin were used as a model drug by electrodeposition method. The resultant coatings were characterized by FTIR, XRD, FESEM, EDAX and AFM techniques. The mechanical behavior of the composite coatings was evaluated using thickness and hardness tester and electrochemical properties were studied in Ringer's solution. Similarly, CIP@PPEDA/TiO2‐SiO2 composite coating on Ti alloy shows good corrosion resistance and better antibacterial efficacy as well as L929 fibroblast cell line, which exhibited a high cell adhesion and high cell viability compared than TiO2‐SiO2 and PPEDA/TiO2‐SiO2 coatings. All these results suggest that, this newly developed composite coating exhibits superior bioactivity and improved anticorrosion performance on Ti specimen and can be a potential candidate for orthopedic applications.

Preparation of hydroxyapatite porous scaffold from a ‘coral-like’ synthetic inorganic precursor for use as a bone substitute and a drug delivery vehicle

A novel surfactant free hydrothermal method was developed for the preparation of large hydroxyapatite scaffolds. Synthetic calcium carbonate (calcite) was used as the starting material which when mixed with an inorganic setting solution containing phosphoric acid and sodium hydroxide forms the porous precursor body with pore size 20–700 μm. The porous precursor body was then hydrothermally converted to hydroxyapatite scaffolds when treated in basic phosphate solution of pH 10.5 at 150 °C and 15 bar pressure maintaining the structural stability and integrity. X-ray diffraction and the Fourier transform infrared spectroscopy confirmed that the developed material consist of single phase crystalline hydroxyapatite. Surface morphology and microstructures were studied using scanning electron microscopy and porosity was evaluated by micro CT analysis. The cell material interactions evaluated by cell viability assays and live cell staining methods confirmed the cell compatibility. The drug release study at physiological pH implied that the developed materials could be promising in sustained long-term release. The results emerged have shown that the hydrothermal conversion of inorganic coral-like precursor is effective to produce porous bioactive hydroxyapatite scaffolds for bone regeneration as well as drug delivery vehicles for the treatment of infectious bone diseases such as osteomyelitis.

Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection.

Bone infection is a common and serious complication in the orthopedics field, which often leads to excessive bone destruction and non‐union. Osteoclast is the only type of cells which have the function of bone resorption. Its over activation is closely related to excessive bone loss. Staphylococcus aureus (S. aureus) is a major pathogen causing bone infection, which can produce a large number of strong pathogenic substances staphylococcal protein A (SPA). However, few studies were reported about the effects of SPA on osteoclastogenesis. In our study, we observed that S. aureus activated osteoclasts and promoted bone loss in bone infection specimens. Then, we investigated the effects of SPA on RANKL‐induced osteoclastogenesis in vitro, the results revealed that SPA promoted osteoclastic differentiation and fusion, and enhanced osteoclastic bone resorption. In addition, we also showed that SPA upregulated the expression of NFATc1 and c‐FOS through the activation of MAPK signaling to promote osteoclastogenesis. Our findings might help us better understand the pathogenic role of S. aureus in bone infection and develop new therapeutic strategies for infectious bone diseases.

Microbial Biofilms Are Able to Destroy Hydroxyapatite in the Absence of Host Immunity In Vitro

It is widely thought that inflammation and osteoclastogenesis result in hydroxyapatite (HA) resorption and sequestrum formation during osseous infections, and microbial biofilm pathogens induce the inflammatory destruction of HA. We hypothesized that biofilms associated with infectious bone disease can directly resorb HA in the absence of host inflammation or osteoclastogenesis. Therefore we developed an in vitro model to test this hypothesis. Customized HA discs were manufactured as a substrate for growing clinically relevant biofilm pathogens. Single-species biofilms of Streptococcus mutans, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and mixed-species biofilms of C albicans plus S mutans were incubated on HA discs for 72 hours to grow mature biofilms. Three different non-biofilm control groups also were established for testing. HA discs were then evaluated by means of scanning electron microscopy, micro-computed tomography metrotomography, x-ray spectroscopy, and confocal microscopy with planimetric analysis. In addition, quantitative cultures and pH assessment were performed. Analysis of variance was used to test for significance between treatment and control groups. All investigated biofilms were able to cause significant (P < .05) and morphologically characteristic alterations in HA structure as compared with controls. The highest number of alterations observed was caused by mixed biofilms of C albicans plus S mutans. S mutans biofilm incubated in medium with additional sucrose content was the most detrimental to HA surfaces among single-species biofilms. Our findings suggest that direct microbial resorption of bone is possible in addition to immune-mediated destruction, which has important translational implications for the pathogenesis of chronic bone infections and for targeted antimicrobial therapeutics.

Bone Substitutes as a Drug Delivery of Antibiotics

The aim of the present study was the in vitro investigation of a synthetic bone graft substitute loaded with individual antibiotics for the treatment of osteomyelitis and infectious bone disease. The elution of gentamicin, an aminoglycoside antibiotic, from the NanoBone® products NanoBone® S granules (NBG) and lyophilized NanoBone® (NBP) putty was tested over a period of one week. An indirect photometrically-based detection system was used to measure the released antibiotic concentration. Both materials showed very different release behaviour. After one day lyophilized NanoBone® putty delivered 100% of the gentamicin value, whereas NanoBone® S granules released one-fifth of the used gentamicin level.

Mediolateral subchondral tibial bone mineral density difference does not predict osteoarthritis progression.

Data on the relationship between osteoporosis and osteoarthritis are conflicting. Most studies report "snapshot" prevalences, and there are few studies evaluating localized knee bone mineral density (BMD) measurements with respect to subsequent osteoarthritis progression. The authors hypothesize that increased mediolateral difference of the proximal tibial BMD may predict progression of knee osteoarthritis. In this study, 246 female volunteers were followed up prospectively over 2 years. Baseline BMD measurements of bilateral proximal (subchondral) tibiae were performed, and the mediolateral BMD ratio was calculated. Precision studies were performed on healthy volunteers to validate the technique. The patients were divided into osteoarthritis progressors and non-progressors based on Kellgren-Lawrence radiographic criteria at 2-year follow-up. Patients who were taking bisphosphonates or who had a history of inflammatory, infectious, or metabolic bone disease and previous hip and knee surgery were excluded. Demographic data, calcium supplementation, physical activity, baseline knee radiographs, and radiographs at 2-year follow-up were obtained. The study was adequately powered to detect an effect size of 0.4. There were 121 progressors and 125 non-progressors. Mean mediolateral BMD ratio was 1.02 among the progressors and 1.01 among the non-progressors (t=0.632, P=.528). Potential confounders were equally distributed among both groups. The data suggest that there is no link between proximal tibial BMD ratio and progression of knee osteoarthritis.

In Vitro Elution Characteristics of Gentamicin and Vancomycin from Synthetic Bone Graft Substitutes

Objects:Beta tricalciumphosphate pellets loaded with individualized antibiotics may represent novel options in the treatment of osteomyelitis and infectious bone disease. Here, the in vitro antibiotic elution of vancomycin and gentamicin from the synthetic bone graft substitutes Cerasorb® and Cerasorb M® was tested. Methods:Antibiotic elution and concentration of gentamcin and vancomycin were measured using photometrically-based measurement and homogeneous particle-enhanced turbidimetric inhibition immunoassays (PETINIA). Results:Initially both materials showed a high release of the loaded antibiotics, with Cerasorb M® showing lower release levels for gentamicin and vancomycin than Cerasorb®. Gentamicin concentrations of Cerasorb M granules and Cerasorb were below the minimum detectiontreshold until day four and six of the experiment respectively. The vancomycin release-level followed a similar pattern, although the vancomycin concentration eluted by Cerasorb M® granules stayed above the detection threshold during the experimental time.Conclusions: Cerasorb® and Cersorb M® may represent a new treatment option in osteomyelitis and infectious bone disease.

In vitro/in vivo comparison of cefuroxime release from poly(ε‐caprolactone)–calcium sulfate implants for osteomyelitis treatment

This study aimed to investigate the release of cefuroxime axetil (CF) and calcium from poly(ε-caprolactone) (PCL)-calcium sulfate (CaS) implants (PCL:CaS 2:1-10% CF; PCL:CaS 2:1-20% CF; PCL:CaS 1:1-10% CF) for treating infectious bone diseases. Bioactivity, crystallinity and strength, and release profiles under standard and pressurized release conditions were studied. PCL:CaS 2:1-20% CF had slower release than 10% loading. These groups had no significant change in CF and Ca release in response to pressure. The PCL:CaS 1:1 group had the slowest release despite having higher CaS, probably due to more compaction of discs. In contrast, pressure caused significant differentiation of CF and Ca(2+) release. The presence of CaS enhanced mechanical properties and bioactivity of discs. SEM and XPS results showed calcium-phosphate containing accumulations on surfaces upon SBF incubation. CF-loaded implants were applied in a rabbit osteomyelitis model. In vivo CF release was enhanced with increased CaS proportions, suggesting that in vivo release conditions are closer to pressurized in vitro conditions. In the control group, there was still some inflammation in the bone and no complete coverage with bone was achieved in the defect site. Discs provided a suitable surface for regeneration of bone. However, bone formation in the PCL:CaS 1:1 disc implanted group was more complete and regular than in the 2:1 group.

277 : Simultaneous measurement of 13 Porcine Cytokines/Chemokines using MILLIPLEX® MAP technology

Cytokines and Chemokines are a group of small proteins that are secreted from immune cells as well as non-immune cells and play important roles in the development of infectious diseases, metabolic diseases, bone diseases and cancer. As porcine becomes a popular animal model used for research in various disease areas, we developed and commercialized MILLIPLEX ® MAP Porcine Cytokines/Chemokines Panel using Luminex® technology for simultaneous measurement of 13 Cytokines/Chemokines (GM-CSF, IFNγ, IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNFα) in porcine serum, plasma and tissue culture samples. Our validation data showed that the assay is specific, sensitive, accurate and reproducible, and this panel detects serum and plasma samples in various porcine strains including Hanford, Yucatan, Gottingen, Sinclair, and Yorkshire. Using this new assay panel, we also measured Cytokine/Chemokine levels in porcine PBMC culture medium samples collected at different time intervals after treatment of LPS or Con A. Our results suggested that this robust multiplex assay panel is a very useful tool for porcine cytokine/chemokine measurement for various research areas and drug discovery.

Dual-delivery of vancomycin and icariin from an injectable calcium phosphate cement-release system for controlling infection and improving bone healing

Infectious bone diseases following severely contaminated open fractures are frequently encountered in clinical practice. It is difficult to successfully repair bone and control infection at the same time. To identify a better treatment method, we prepared a dual-drug release system that was comprised of icariin (IC, a natural osteoinductive molecule), vancomycin (VA) and injectable calcium phosphate cement (CPC). The ultrastructure of the dual-drug release system was evaluated by scanning electron microscopy and the biocompatibility was assessed by cell culture. In addition, the release kinetics of IC and VA were respectively investigated by using high‑performance liquid chromatography. Finally, this system was used to repair Staphylococcus aureus-contaminated bone defects in a rabbit model. Twelve weeks after the implantation of IC-VA/CPC, the contaminated bone defects were completely repaired, with significantly improved formation of lamellar bone and recanalization of the marrow cavity compared with the controls (CPC without antibiotics or osteoinductive agent). These results demonstrate that this dual-drug release system, with its concomitant antibiotic and osteoinductive properties, has significant potential for the treatment of contaminated bone injury or infectious bone disease.

Unusual aetiology of persistent back pain in a patient with multiple myeloma: infectious discitis.

A 47 year old man with multiple myeloma presented with persistent back pain caused by infectious discitis. Aspiration of the affected vertebral disc space was carried out, guided by computed...