Bone is a common and debilitating site for metastatic cancer cell expansion. Skeletal metastasis is a multistage process, with primary stages of circulating tumour cells, progressing to a dormant state in vasculature and bone marrow niches, followed by tumourigenic reactivation, proliferation and finally bone destruction. The frequency of bone metastasis is reconciled in Paget’s ‘seed and soil’ hypothesis, where a conducive microenvironment (bone niche) is essential for cancer cell colonisation. Cancer cells can mimic bone cells (osteomimicry) and interact with the bone marrow’s vascular architecture, utilising pathways akin to haematopoietic stem cell expansion. Current research suggests that each phase of bone metastasis is associated with specific gene expression and protein abundance patterns. For example, E-selectin, CXCR-4 and CXCL-12 are crucial for cancer cell homing, dormancy and colonisation of bone tissue. In contrast, different primary cancers appear to have unique staging profiles. In prostate cancer, dormancy is modulated by the CXCR-4/CXCL-12, ANXA2/CXCL12 and GAS6 pathways, while in breast cancer, dormancy involves ERK1/2, p38, MSK1, LIF, BMP-7, TGF-β1/2 and bone resorption factors. Conversely, osteoblastic metastasis in both breast and prostate cancers is characterised by ET-1, Dkk1 suppression and the release of IL-6, MCP-1, VEGF, FGF and IGF, while osteolytic metastasis primarily depends on PTHrP, RANKL, OPG, TGF-β, IGF, TNF-α, IL-1 and IL-7. Understanding the complex molecular mechanisms facilitating cancer cell colonisation and expansion in bone tissues is essential for developing effective treatments to prevent bone metastases. In this review, we discuss current theories linking bone remodelling with bone.

Background: The benefits of exercise for patients with cancer are well-established, however, for patients with bone metastases, exercise as adjuvant therapy is underutilised due to concerns for safety, efficacy and other barriers such as the method of delivery. This scoping review explores these barriers by reviewing the results of clinical trials conducted on participants with bone metastases. Methods: A thorough literature search was undertaken using PubMed, Scopus, NIH Clinical Trials and Google Scholar databases. Articles that involved an exercise intervention and patients with bone metastases were included. Data were pooled, charted, analysed and reported according to PRISMA-ScR standards. Results: A total of 26 trials were reviewed with interventions that included aerobic and resistance training. Only three serious adverse events occurred, not likely related to bone metastases. Nine trials (34.6%) involved unsupervised exercise sessions. Remote exercise delivery had an average of 80.3% compliance, rivalling in-person and mixed supervision. The results of this review reaffirm that exercise helps improve functional capacity, muscle strength, lean mass and cardiovascular function, and is safe in patients with bone metastases irrespective of in-person or remote delivery. Conclusions: Exercise therapy, whether delivered in person or remotely, is safe and efficacious for patients with bone metastases.

Rodent models of Down syndrome (DS) have been transformative in identifying basic mechanisms underlying the effects of Trisomy 21 at the molecular, cellular, physiological, and neurobehavioral levels. Each model, with its unique genomic architecture, has advanced our understanding of the complex multisystem etiology of DS. The availability of multiple models necessitates the challenge of selecting appropriate models to address a particular scientific question, experimental design, and translational relevance. This primer guides the reader through the various rodent models of DS and the genomic and phenotypic effects they recapitulate. We also provide recommendations and strategies for using DS rodent models to enable effective and robust forward and reverse translational approaches.

Metastasis from breast cancer (BC) has a predilection for the skeleton. Due to its osteolytic nature, breast cancer bone metastasis (BCBM) appears to increase fracture risk. The association between obesity and its effect on bone seems to be skeletal site-specific. The incidence of pathological fractures often involves the axial skeleton even though the most debilitating effects of fractures are caused in the appendicular skeleton. Whether obesity increases fracture risk in BCBM remains inconclusive, however. At present, there is no literature that examines the effects of obesity on BCBM, and fracture risk are as such we sought to determine the effect of obesity on fracture risk in BC. This is the focus of the review. This scoping review aims to examine the link between fracture outcomes of women with BC and obesity as reported by Body Mass Index (BMI). The purpose of this study is to determine if current literature suggests obesity increases fracture risk in women with BC. We conducted a comprehensive literature search for breast cancer bone metastasis, obesity, and fracture risk in PubMed, Cochrane Library, NIH Clinical Trials, and OpenGrey. Articles that included BC, obesity, and fracture risk were included for analysis. Data were pooled, charted, analysed, and reported according to PRISMA-ScR standards. Each outcome was stratified by BMI (obese or non-obese) status in women with breast cancer. Five studies were eligible for analysis and relevant data was charted to allow results to be synthesised. We found four out of five studies reported a positive association between BMI and fracture risk in females with breast cancer. We found a potential association of obesity and fracture risk in breast cancer. However, as we conducted this study it was evident that there is limited literature available on this topic and none for breast cancer bone metastasis. This poses an important direction for future research. Larger and robust pre-clinical and clinical randomized control trials are needed to better understand the relation between obesity and metastatic breast cancer.