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Bone metastases

Nature Reviews Disease Primers volume 6, Article number: 83 (2020) Cite this article

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Abstract

Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary tumour site and colonize the bone microenvironment. Within the bone, these disseminated tumour cells, as well as those arising in the context of multiple myeloma, may assume a state of dormancy, remaining quiescent for years before resuming proliferation and causing overt metastasis, which causes bone destruction via activation of osteoclast-mediated osteolysis. This structural damage can lead to considerable morbidity, including pain, fractures and impaired quality of life. Although treatment of bone metastases and myeloma bone disease is rarely curative, disease control is often possible for many years through the use of systemic anticancer treatments on a background of multidisciplinary supportive care. This care should include bone-targeted agents to inhibit tumour-associated osteolysis and prevent skeletal morbidity as well as use of appropriate local treatments such as radiation therapy, orthopaedic surgery and specialist palliative care to minimize the impact of metastatic bone disease on physical functioning. In this Primer, we provide an overview of the clinical features, the pathophysiology and the specific treatment approaches to prevent and treat bone metastases from solid tumours as well as myeloma bone disease.

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Fig. 1: Metastatic invasion of cancer cells to the bone.
Fig. 2: Physiological bone remodelling.
Fig. 3: Osteolytic bone metastases.
Fig. 4: Osteoblastic bone metastases.
Fig. 5: Myeloma bone disease.
Fig. 6: Relationships between imaging technologies and cellular biology of bone metastasis.
Fig. 7: Comparison of imaging techniques used for the diagnosis of bone metastases.
Fig. 8: Schematic algorithm for multidisciplinary treatment of bone metastases and myeloma bone disease.
Fig. 9: Bone metastasis response assessments on whole-body MRI.

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Acknowledgements

P.I.C. acknowledges J. Gibson and the Ernest Heine Family Foundation, the Kay Stubbs Cancer Research Grant, the Cancer Council New South Wales, the Leukaemia Foundation, the Prostate Cancer Foundation of Australia, The Movember Foundation and the National Health and Medical Research Council for supporting his research. P.C. acknowledges INSERM, ‘Appel à Projets LIA/LEA 2016’ (grant no.: ASC17018CSA), Weston Park Cancer Charity (grant no.: CA163) and the LabEX DEVweCAN (ANR-10-LABX-61) from Université de Lyon, within the programme ‘Investissements d’Avenir’ (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR), for funding his research.

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Authors and Affiliations

  1. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    Robert E. Coleman & Philippe Clézardin

  2. Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia

    Peter I. Croucher

  3. St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia

    Peter I. Croucher

  4. Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Northwood, UK

    Anwar R. Padhani

  5. INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, University of Lyon, Lyon, France

    Philippe Clézardin

  6. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

    Edward Chow

  7. Edinburgh Cancer Research Centre (IGMM), University of Edinburgh, Edinburgh, UK

    Marie Fallon

  8. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Theresa Guise

  9. Department of Translational Research on New Surgical and Medical Technologies, University of Pisa, Pisa, Italy

    Simone Colangeli & Rodolfo Capanna

  10. Hospital de Santa Maria and Instituto de Medicina Molecular, Faculdade de Medicina, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal

    Luis Costa

Authors
  1. Robert E. Coleman
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  2. Peter I. Croucher
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  3. Anwar R. Padhani
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  4. Philippe Clézardin
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Contributions

Introduction (R.E.C.); Epidemiology (R.E.C., L.C.); Mechanisms/pathophysiology (R.E.C., P.I.C., T.G.); Diagnosis, screening and prevention (R.E.C., A.R.P.); Management (R.E.C., E.C., L.C., M.F., A.R.P., S.C., R.C.); Quality of life (R.E.C.); Outlook (R.E.C., P.C.); Overview of Primer (R.E.C.).

Corresponding author

Correspondence to Robert E. Coleman.

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Competing interests

R.E.C. has received honoraria from Amgen and Novartis, and has stock options with Inbiomotion related to a patented biomarker. P.I.C. is the recipient of a grant from Amgen, and received honoraria and participated in advisory boards from Amgen. P.C. has received honoraria from Amgen. L.C. has received research grants from Amgen, Bayer, Novartis and Roche, speaker honoraria from Amgen, Bayer, Janssen, Lilly and Roche, and is also a consultant for Amgen, Novartis and Servier. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks Jean-Yves Blay, Claire Edwards, Rachelle Johnson, Klaus Pantel, Julie Sterling and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Bone resorption

The breakdown or dissolution of bone by osteoclasts.

Osteoclasts

Multinucleated cells derived from granulocyte–macrophage precursors that break down (resorb) bone.

Osteoblast

A bone-forming cell derived from mesenchymal, fibroblast-like cells that forms bone and usually works in close collaboration with osteoclasts to ensure bone resorption and formation are linked and balanced.

Bisphosphonates

A class of drugs that prevent bone loss by disrupting osteoclast-mediated bone resorption.

Denosumab

A fully humanized monoclonal antibody that binds to receptor activator of nuclear factor-κB ligand (RANKL) and inhibits osteoclast-mediated bone resorption.

Axial skeleton

The central portion of the skeleton comprising the skull, spine, pelvis, shoulders, hips and ribs.

Exosomes

Extracellular vesicles that may contain proteins, RNA or DNA.

Bone turnover

A measure of the speed of bone resorption and formation as determined by biomarkers or bone biopsy.

Endosteum

A thin vascular membrane of connective tissue that lines the inner surface of the bony tissue that forms the medullary cavity of long bones.

Leukoerythroblastic anaemia

Anaemia resulting from a structural or neoplastic problem in the bone marrow and the resultant appearance of immature erythrocyte and white cell precursors in the peripheral blood.

Diffusion weighted imaging

A form of MRI based upon measuring the random Brownian motion of water molecules within a voxel of tissue. Highly cellular tissues or those with cellular swelling exhibit lower diffusion coefficients.

Castration-resistant prostate cancer

(CRPC). A phase in the evolution of advanced prostate cancer that progresses despite androgen deprivation therapy.

Castration-sensitive prostate cancer

Prostate cancer that can be controlled by lowering androgen levels.

Oligometastasis

A single site or a few (<5) sites of metastasis within up to three different metastatic sites.

Curettage

Removal of tissue by scraping or scooping rather than surgical resection.

Analgesic titration

A stepwise increase in analgesics, especially opioids, to achieve pain control without excessive toxicity.

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Coleman, R.E., Croucher, P.I., Padhani, A.R. et al. Bone metastases. Nat Rev Dis Primers 6, 83 (2020). https://doi.org/10.1038/s41572-020-00216-3

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