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The Pathophysiology of Myeloma Bone Disease: Bone Remodelling and the Role of Osteoclasts

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Management of Bone Disease and Kidney Failure in Multiple Myeloma

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Abstract

One of the most devastating effects of multiple myeloma is the severe bone disease that affects over 80% of patients during their disease course. In the vast majority, this is irreversible and significantly adds to the already heavy disease burden. Over the last decade, the pathophysiology and complexity of bone destruction in myeloma have become increasingly evident, here we explore the multiple normal physiological pathways and cell types that are disrupted in myeloma and can therefore be implicated in the evolution of bone destruction in this disease. As these pathways become clearer, they open up the possibility of targeted interventions which are explored elsewhere in this text.

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Abbreviations

ALP:

Alkaline phosphatase

BAFF:

B-cell-activating factor

bALP:

Bone alkaline phosphatase

BM:

Bone marrow

BMD:

Bone mineral density

BMME:

Bone marrow microenvironment

BMP-2:

Bone morphogenetic protein-2

BMSC:

Bone marrow stromal cells

CBFA1:

Core-binding factor Runt domain α subunit 1

CCL3:

Chemokine (C-C motif) ligand 3

DcR3:

Decoy receptor 3

DKK1:

Dickopf-1

FRP:

Frizzled-related proteins

Gfi1:

Growth factor independence 1

HGF:

Hepatocyte growth factor

IL-:

Interleukin-

LRP:

Low-density lipoprotein receptor-related protein

MBD:

Myeloma bone disease

MGUS:

Monoclonal gammopathy of unknown significance

MIP:

Macrophage inflammatory protein

MM:

Multiple myeloma

MMP:

Matrix metalloproteinase

MPC:

Malignant plasma cell

NF κB:

Nuclear factor kappa B

OAFs:

Osteoclast-activating factors

OB:

Osteoblast

OC:

Osteoclast

OIFs:

Osteoblast-inhibiting factors

OP:

Osteoporosis

OPG:

Osteoprotegerin

PTH:

Parathyroid hormone

PTHrP:

Parathyroid hormone-related protein

RANK:

Receptor activator of nuclear factor kappa B

RANKL:

Receptor activator of nuclear factor kappa B ligand

Runx2:

Runt-related transcription factor 2

SDF-1 α:

Stromal cell-derived factor 1 α (also known as CXCL12)

sFRP-:

Secreted frizzled-related protein-

SRE:

Skeletal-related events

TGF-β:

Transforming growth factor-beta

TNF:

Tumour necrosis factor

TRAF6:

TNF receptor-associated factor 6

TRAIL:

TNF-related apoptosis-inducing ligand

VCAM1:

Vascular cell adhesion molecule-1

VLA4:

Very late antigen 4 (also known as α4β1 integrin)

WIF-1:

Wnt inhibitory factor 1

Wnt:

Wingless/Intergrase-1

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Authors and Affiliations

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

    Rebecca E. Andrews & Andrew D. Chantry

  2. Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK

    Rebecca E. Andrews & Andrew D. Chantry

  3. Mid Yorkshire NHS Trust, Wakefiled, UK

    A. John Ashcroft

  4. University of Leeds, Leeds, UK

    A. John Ashcroft

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  1. “Seràgnoli” Institute of Hematology, IRCCS, Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy

    Elena Zamagni

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Andrews, R.E., Chantry, A.D., Ashcroft, A.J. (2021). The Pathophysiology of Myeloma Bone Disease: Bone Remodelling and the Role of Osteoclasts. In: Zamagni, E. (eds) Management of Bone Disease and Kidney Failure in Multiple Myeloma. Springer, Cham. https://doi.org/10.1007/978-3-030-63662-3_2

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  • DOI: https://doi.org/10.1007/978-3-030-63662-3_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-63661-6

  • Online ISBN: 978-3-030-63662-3

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