Aims. The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Methods. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. Results. IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. Conclusion. Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP. Cite this article: Bone Joint Res 2022;11(11):803–813

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340

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

The April 2024 Oncology Roundup³⁶⁰ looks at: Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis; Intraosseous conventional central chondrosarcoma does not metastasize irrespective of grade in pelvis, scapula, and in long bone locations; Oncological and functional outcomes after resection of malignant tumours of the scapula; Reconstruction following oncological iliosacral resection – a comparison of techniques; Does primary tumour resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis?; Older patients with Ewing’s sarcoma: an analysis of the National Cancer Database; Diagnostic challenges in low-grade central osteosarcoma; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 limb soft-tissue sarcoma patients: a retrospective analysis using inverse probability of treatment weighting-adjusted models.

The October 2023 Oncology Roundup³⁶⁰ looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.

Aims

The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa.

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

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

Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs.

Aims

Surgery is often indicated in patients with metastatic bone disease (MBD) to improve pain and maximize function. Few studies are available which report on clinically meaningful outcomes such as quality of life, function, and pain relief after surgery for MBD. This is the published protocol for the Bone Metastasis Audit — Patient Reported Outcomes (BoMA-PRO) multicentre MBD study. The primary objective is to ascertain patient-reported quality of life at three to 24 months post-surgery for MBD.

Aims

Echocardiography is commonly used in hip fracture patients to evaluate perioperative cardiac risk. However, echocardiography that delays surgical repair may be harmful. The objective of this study was to compare surgical wait times, mortality, length of stay (LOS), and healthcare costs for similar hip fracture patients evaluated with and without preoperative echocardiograms.

Aims

Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells.

Aims

As the peak of the COVID-19 pandemic passes, the challenge shifts to safe resumption of routine medical services, including elective orthopaedic surgery. Protocols including pre-operative self-isolation, COVID-19 testing, and surgery at a non-COVID-19 site have been developed to minimize risk of transmission. Despite this, it is likely that many patients will want to delay surgery for fear of contracting COVID-19. The aim of this study is to identify the number of patients who still want to proceed with planned elective orthopaedic surgery in this current environment.

Objectives

Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells.

Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities.

We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240).

The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage.

The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage.

Cite this article: Bone Joint J 2014; 96-B:1396–1403

The April 2014 Oncology Roundup³⁶⁰ looks at: Eyeball as good as microscope for tumour margins; when is best to stabilise femoral metastases?; fluorine does not cause bone tumours; whether giant cell tumour of the proximal femur ever successfully managed; extraskeletal osteosarcoma; modular lower limb tumour reconstruction; and observational studies the basis for most bone tumour treatment.

Objectives

Guidelines for the management of patients with metastatic bone disease (MBD) have been available to the orthopaedic community for more than a decade, with little improvement in service provision to this increasingly large patient group. Improvements in adjuvant and neo-adjuvant treatments have increased both the number and overall survival of patients living with MBD. As a consequence the incidence of complications of MBD presenting to surgeons has increased and is set to increase further. The British Orthopaedic Oncology Society (BOOS) are to publish more revised detailed guidelines on what represents ‘best practice’ in managing patients with MBD. This article is designed to coincide with and publicise new BOOS guidelines and once again champion the cause of patients with MBD.

The October 2012 Oncology Roundup³⁶⁰ looks at: the causes of primary bone tumours; adjuvant chemotherapy in the longer term; vascularised fibular grafts to salvage massive femoral allografts; a new look at old risks; reconstruction with excised irradiated bone; predicting chemosensitivity in osteosarcoma ; and chemotherapy, osteoporosis and the risk of fracture.