Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

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Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.

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The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

1. A case of symmetrical bilateral calcareous bursitis at the elbow is described. 2. Metabolic and neurotrophic factors played a role in its genesis. 3. Chemical analysis showed a similarity between the ratio of calcium phosphate and calcium carbonate in dystrophic calcification and in the fluid in the bursal cavity. 4. An inflammatory reaction was seen around the calcium appearing interstitially: this was probably not a consequence of chemical stimuli

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To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients.

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This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

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This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Aim. Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results. We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion. We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

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Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

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Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

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The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS.

Objective . A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation. Method . A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months. . Results . Systemic exposure to gentamicin after implantation was very low as local gentamicin concentrations were measured in wound exudate after six to ten hours. There were no signs of infectious complication throughout the clinical phase. Four patients had recurrent infections several weeks to months after implantation. The outcome was deemed successful by remission of infection in 16 (80%) of these problematic long-term treated patients. Safety laboratory measurements did not indicate nephrotoxic or hepatotoxic effects. . Conclusions . Local application of calcium sulphate/carbonate bone void filler comprising gentamicin revealed sufficient active local levels of the antibiotic by simultaneous significant low systemic exposure in patients with mostly chronic osteomyelitis/osteitis. The material was safe and well tolerated. Cite this article: Bone Joint Res 2014;3:223–9

1. The influence of various methods of preserving bone on the calcifying mechanism of the tibial epiphysial cartilage of rachitic rats was studied. An in vitro calcification technique was employed. 2. Preservation by deep freezing, aqueous merthiolate, boiling, or acetone inactivated the calcifying mechanism. 3. The inactivation was reversed with calcium ions, most readily in the deep-frozen bones, less readily in the merthiolate treated bones, still less readily in the acetone stored bones, and least in boiled bones. 4. Exposure to calcium ions before preservation in the deep-freeze chest prevented inactivation. 5. The inactivation, reactivation and survival of the calcifying mechanism were confirmed by metachromasia studies. 6. The theory of the mode of action of calcium chloride on reactivation and survival of the calcifying mechanism is presented

Extraskeletal bone formation can be induced in rodents by implantation of demineralised bone matrix and such implantation has been used to treat bone defects in man, but it is uncertain if induction or merely conduction occurs. We studied bone induction in primates by excising segments of the fibulae of adult squirrel monkeys, defatting and demineralising them before reimplanting them into the quadriceps of the same animal. As a control experiment, rat matrix was prepared in exactly the same way and implanted in rats. After six weeks the implants were harvested and either ashed and analysed for calcium content or prepared for histology. In the rats, the calcium content indicated that about 20% of the original matrix had been replaced by new bone. In the monkeys the calcium content was about the same as that in normal body fluid and no bone was seen in histological sections. This result casts doubt on the use of demineralised human bone matrix as a bone inductor, although it may function by other mechanisms

Ceramics have many properties which might make them suitable alternatives to bone grafts. This present study was done to find a suitable biodegradable porous ceramic for human bone replacement. Three different porous ceramics (calcium aluminate, calcium hydroxyapatite and tricalcium phosphate), with interlinked pores of two size ranges (150 to 210 micron), were implanted into the skulls of rats and rabbits for up to six months; the interaction with surrounding bone, which is virtually devoid of bone marrow, was then assessed. The ceramics caused no adverse biological response. Tissue ingrowth into pores throughout the implant was seen in all three types and in both pore sizes of ceramic, but the density of the penetrating tissue was far less for calcium aluminate than for calcium hydroxyapatite or tricalcium phosphate. For each type of ceramic, the soft-tissue ingrowth was more dense with the larger pore size, and with a longer period of implantation. Bone ingrowth was not usually seen within the pores of any ceramic. There were no differences in the histological findings between the rats and the rabbits. The results demonstrate that it is possible to produce ceramic materials with a porous structure which allows ingrowth of tissue and biological fluids

Aims. Treatment guidelines for atypical femoral fractures associated with bisphosphonates have not been established. We conducted a systematic review of the treatment of atypical femoral fractures first, to evaluate the outcomes of surgical fixation of complete atypical fractures and secondly, to assess whether prophylactic surgery is necessary for incomplete atypical fractures. Materials and Methods. Case reports and series were identified from the PubMed database and were included if they described the treatment of atypical femoral fractures. In total, 77 publications met our inclusion criteria and 733 patients with 834 atypical complete or incomplete femoral fractures were identified. Results. For complete fractures, internal fixation was predominantly achieved by intramedullary nailing. The mean time to healing post-operatively was 7.3 months (2 to 31). Revision surgery for nonunion or implant failure was needed in 77 fractures (12.6%). A greater percentage of fractures treated with plate fixation (31.3%) required revision surgery than those treated with intramedullary nailing (12.9%) (p < 0.01). Non-operative treatment of incomplete fractures failed and surgery was eventually needed in nearly half of the patients (47%), whereas prophylactic surgery was successful and achieved a 97% rate of healing. Conclusion. Intramedullary nailing is the first-line treatment for a complete fracture, although the risk of delayed healing and revision surgery seems to be higher than with a typical femoral fracture. Non-operative treatment does not appear to be a reliable way of treating an incomplete fracture: prophylactic intramedullary nailing should be considered if the patient is in intractable pain. Radiographs of the opposite side should be obtained routinely looking for an asymptomatic fracture. Bisphosphonates must be discontinued but ongoing metabolic management in the form of calcium and/or vitamin D supplements is advisable. Teriparatide therapy can be considered as an alternative treatment. Cite this article: Bone Joint J 2017;99-B:295–302

1. Senile osteoporosis is one of the common causes of morbidity in old people. Its distribution in European and American populations has been deduced from epidemiological studies of its major complications, such as fractures of the vertebrae and the femoral neck. Although there has been some evidence that different population groups differ in their susceptibility to this condition, no demographic study of its prevalence in the white and Bantu races has previously been made. 2. The present paper describes an epidemiological study of femoral neck fractures in the Bantu population of Johannesburg, covering the years 1957-63. The cases were analysed by age and sex, the type of trauma and the level of the fracture. The number of fractures was related to the population at risk; the fracture incidence was expressed both as an age-specific rate and as a standardised rate and compared with fracture rates in European populations. It was found that the fracture rate in the elderly Bantu is less than one-tenth of that in Western European populations, and that males and females are affected equally. It was concluded that senile or post-menopausal osteoporosis is much less pronounced in the Bantu than in white populations. 3. The relationship of these findings to endocrine changes, calcium balance and racial factors is discussed. It is suggested that senile osteoporosis is not caused by a simple calcium deficiency but may be related to an imbalance between calcium intake, absorption and excretion, or a failure of the complex mechanism which normally controls this balance. Whatever the immediate cause, however, race plays an important part in determining the onset and distribution of the condition

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Aims

Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.