Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.

1. Experiments to examine the antigenicity of homologous bone tissues in rats are reported. The tissues studied included fresh marrow-free cortical bone blocks and chips, fresh, boiled, frozen and freeze-dried marrow-containing iliac bone, fresh iliac bone devoid of marrow, and fresh red marrow. 2. The various tissues were transplanted from hooded to Wistar rats. Three weeks later a skin graft from each donor was transplanted to its respective host to detect the presence of transplantation immunity, which was indicated by the early rejection of the skin graft. 3. Homografts of fresh cortical bone evoked transplantation immunity indicating that it contained transplantation antigens which were also in the skin. 4. Homografts of fresh marrow-containing iliac bone also evoked transplantation immunity, which was shown to be caused by the red marrow. 5. Fresh iliac homografts devoid of marrow did not elicit transplantation immunity. This suggests that iliac bone tissue may not contain transplantation antigens or that the small amount of iliac bone inserted was insufficient. 6. Microscopy of the grafts, removed after three weeks, showed that the inflammatory infiltrations around the bone homografts and autografts were not very different, but that the amount of new bone formed was different. The autografts produced a lot of new bone, the homografts only a little. 7. It is suggested that the immune response evoked in the host by the foreign graft impairs the formation of new bone by fresh homografts of cortical blocks, cortical chips and marrow-containing iliac bone. 8. The impairment of new bone formation by homografts of marrow-free iliac bone is discussed. Such bone grafts fail to evoke detectable transplantation immunity. Why these grafts do not form more new homologous bone than the other homografts studied, is not clear. 9. Homografts of boiled and frozen iliac bone do not evoke any detectable change in the sensitivity of the host to donor tissue. 10. Homografts of freeze-dried marrow-containing iliac bone elicit a slight but significant prolongation of the survival of skin homografts. The implication, in terms of modern immunological theory, is that in such grafts certain tissue antigens still persist

When large daily doses of vitamin D were administered to rats endochondral growth was inhibited and bone resorption occurred; later in the process uncalcified matrix (osteoid) like that seen in rickets formed on trabecular margins. When vitamin D was given only for a short period and then discontinued, little resorption of bone was seen during the withdrawal period and wide seams of osteoid material appeared which eventually calcified in an irregular manner. When normal endochondral growth was resumed a wide transverse band of dense bone with enclosed cartilaginous cores was left in the marrow cavity. If, after a few days, a second large dose of the vitamin was given resorption again occurred and calcification of osteoid material was accelerated, the first microscopic sign being a dense, wide, granular, deeply staining line at the junction of the bone and new osteoid. After a second withdrawal period a second layer of osteoid formed; eventually another transverse band appeared in the metaphysis. If this hypervitaminosis D cycle (+4 -12) was continued rats continued to form new bone with relatively little remodelling, so that after three such cycles bones became dense and hard. Histological study showed that little marrow cavity remained in either skull, vertebrae or epiphyses and a dense mass of bone enclosing cartilage cores filled the metaphysial part of the long bones. In addition, ankylosis ofteeth, calcification of spinal ligaments and widespread metastatic calcification were present. When hypervitaminosis D cycles (+1 -12, +1 -21) were adjusted to produce minimal resorptive changes a wide range of bone change was observed. This varied from uniform dense metaphysial bone containing abnormal cartilage matrix arranged in longitudinal striations, dense transverse bands parallel to the epiphysial cartilage, to remnants of dense trabeculae extending into the marrow cavity. Bone changes in osteopetrosis structurally closely resembled the induced bone changes in the rat. It is concluded that an important mechanism in the production of osteopetrosis is an accentuated rhythm of bone change like that shown experimentally to be produced in these animals. It is emphasised that these changes are but part of a range of bone disorders associated with abnormalities of cycles of resorption and deposition of bone, the type of change differing with the nature of the cycles

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

Objectives

Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation.

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Aims

To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice.

Objectives

Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures.

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Objectives

Irrigation is the cornerstone of treating skeletal infection by eliminating pathogens in wounds. A previous study shows that irrigation with normal saline (0.9%) and ethylenediaminetetraacetic acid (EDTA) could improve the removal of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) compared with normal saline (NS) alone. However, it is still unclear whether EDTA solution is effective against infection with drug-resistant bacteria.

The efficacy of locally implanted antibiotic-calcium hydroxyapatite ceramic composites was investigated for the treatment of experimentally produced, implant-related osteomyelitis in rats. High concentrations of antibiotics were detected at the site of infection and bacteria were eradicated without removal of the metal implants. Parenteral antibiotics and surgical debridement, alone or in combination with antibiotic-impregnated acrylic bone cement, all failed to eradicate the infections

1. Reports of the lipaemia-clearing effect of heparin suggested that this drug might be of therapeutic value in fat embolism. 2. In an experimental trial with rats, heparin was found both to accelerate death and to increase the number of deaths after fat embolism. 3. It is accordingly concluded that a clinical trial of heparin in human fat embolism would not be warranted

1. The effects of frozen irradiated homogenous bone grafts on the healing of circumscribed defects in the mandibles and femora of forty albino rats have been studied. 2. The grafts were well tolerated by the host animals and did not appear in any way either to stimulate or to inhibit osteogenesis. The rate of healing of the defects containing the homografts compared favourably with that of the control defects

This paper describes a procedure of activating osteogenesis by the use of the "petal" technique. The osteogenetic effect of these "petals" has been established in experimentally produced fractures and pseudarthroses in rats by radiographical, biomechanical, mechanical and histological examinations. The conventional concept of the osteogenetic activity of bone transplants is discussed. The authors feel that this method will find its clinical application in the operative treatment of pseudarthroses and, in selected cases, of fractures that are known for their tendency to unite slowly

1 . The repair of a simple crush injury was studied in rats, in both normally innervated and completely denervated muscle. In each case the histological findings at periods from two hours to thirty-two weeks are described. 2. The denervated muscle showed active and effective repair. 3. A comparison with the findings in normally innervated muscle establishes that the cellular processes of repair do not depend on connections with the central nervous system

1. Experimental fracture callus in rats contains mast cells as a normal morphological element. 2. The mast cell count undergoes peculiar variations in the normal course of events in experimentally delayed or accelerated bone repair. 3. A hypothesis is presented in which the tissue mast cell granules are regarded as calcium transporters in the mineral phase of callus formation, a process probably corresponding to Selye's concept of "mastocalciphylaxis" and "mastocalcergy."

Aims

Induction heating is a noninvasive, nonantibiotic treatment modality that can potentially be used to cause thermal damage to the bacterial biofilm on the metal implant surface. The purpose of this study was to determine the effectiveness of induction heating on killing Staphylococcus epidermidis from biofilm and to determine the possible synergistic effect of induction heating and antibiotics.