We have attempted to summarise in a short space investigations that have occupied several years, and we realise that whatever the merits of such an effort the results can only be modest. Many important aspects of the osteogenetic process still remain a mystery and thus are subjected to theory and controversy. Such is the case with this constant attendant at osteogenesis which is alkaline phosphatase. But of one thing we are certain, namely that bone is an organised "soft" tissue of which only part has been made rigid by the deposit of calcium salts. The organiser is the osteogenetic vessel from which springs the syncytial frame of cells and their connections on which the bone architecture is established. Endothelial cell, intermediate cell, osteoblast, osteocyte, osteoclast; these constitute the normal sequence of cellular phylogeny in the constant elaboration and removal of the bone substance. The initial cells on which the whole process rests are those of the capillary-sinusoid vessel which is responsible for providing the transudates on which the life and health of the whole syncytium depends. If our findings were confirmed, a better understanding of the nature and characteristics of primitive malignant bone tumours would be possible. Each type of tumour from endothelioma to malignant osteoclastoma, including reticulum-cell sarcoma and osteogenic sarcoma, would be initiated by a different cell of the syncytium, but in its monstrous deviation from the normal would still preserve most of the characteristics of its healthy ancestor. Thus the endothelioma causes bone expansion, bone reaction and even bone necrosis, but not proper bone formation, whereas the osteogenic sarcoma or osteoblastoma forms bone; and with the same fidelity to their origin osteoclasts are seen in the malignant osteolytic tumour. Over thirty years ago the late Sir Arthur Keith (1927) expressed his suspicion that the cells which assume a bone-forming role are derived from the endothelium of the capillary system. We hope we have contributed to show that his suspicion was right

Aims

This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

1. The clinical features, diagnosis and treatment of osteomalacia are discussed in relation to thirty-seven recently recognised cases. It is suggested that this disease is not uncommon in elderly women, among whom it is liable to be confused with senile osteoporosis. Osteomalacia may be distinguished by, firstly, the history, in which persistent skeletal pain of long duration and muscular weakness are typical of osteomalacia, but not of osteoporosis in which transient episodes of pain usually associated with a fracture are more characteristic. There is a high incidence of previous gastric surgery in the osteomalacia patients. Secondly, the physical examination shows skeletal tenderness in osteomalacia but this is not a particular feature of osteoporosis. A shuffling "penguin gait" suggests osteomalacia. Thirdly, the biochemistry shows a low plasma calcium and phosphate, and raised alkaline phosphatase levels commonly in osteomalacia but these are usually normal in osteoporosis. Reduced twenty-four-hour urinary calcium is characteristic of osteomalacia but not of osteoporosis. Fourthly, radiology will show diminished bone density which is common to both diseases, but if the changes are more marked in the peripheral bones than in the axial skeleton osteomalacia is suggested; the opposite is typical of osteoporosis. Skeletal deformity without fracture suggests osteomalacia, as do stress fractures and greenstick fractures in the elderly. Looser's zones are diagnostic of osteomalacia in which they are the most important radiological feature. Finally, histology will show the presence of excess osteoid tissue in undecalcified sections of bone in osteomalacia. This may be the earliest and most sensitive index of the disease and biopsy is indicated in all doubtful cases. 2. The etiology is discussed and it is suggested that a dietary deficiency of vitamin D, limited exposure to sunlight and mild degrees of malabsorption may all be important either alone or in combination. No satisfactory explanation is offered for the predominant female incidence. 3. A practical method of treatment is given and the dangers of uncontrolled administration of vitamin D indicated. 4. Treatment of osteomalacia is rapidly and consistently successful, and well justifies a thorough screening of all elderly patients presenting with weakness, skeletal pain, pathological fractures or with diminished radiographic density of bone

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients.

Cite this article: Bone Joint J 2022;104-B(8):915–921.

Cite this article: Bone Joint Res 2023;12(5):311–312.

Aims

To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

The April 2024 Research Roundup³⁶⁰ looks at: Prevalence and characteristics of benign cartilaginous tumours of the shoulder joint; Is total-body MRI useful as a screening tool to rule out malignant progression in patients with multiple osteochondromas?; Effects of vancomycin and tobramycin on compressive and tensile strengths of antibiotic bone cement: a biomechanical study; Biomarkers for early detection of Charcot arthropathy; Strong association between growth hormone therapy and proximal tibial physeal avulsion fractures in children and adolescents; UK pregnancy in orthopaedics (UK-POP): a cross-sectional study of UK female trauma and orthopaedic surgeons and their experiences of pregnancy; Does preoperative weight loss change the risk of adverse outcomes in total knee arthroplasty by initial BMI classification?.

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Cite this article: Bone Joint Res 2024;13(9):462–473.

Aims

LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling.

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.