Advances in the biology and treatment of bone disease in multiple myeloma

Noopur Raje, G. David Roodman

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Osteolytic bone disease is pathognomonic of multiple myeloma (MM) and affects more than 80% of patients. Bone disease results in skeletal-related events (SRE) such as vertebral compression fractures, which may cause cord compression, hypercalcemia, pathologic fractures that require radiation or surgical fixation, and severe pain. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. Osteolytic disease is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Bisphosphonates are a well-established treatment of myeloma-related skeletal disease and are the current standard of care. However, complications arising from their long-term use have prompted studies of schedule optimization and alternate strategies. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition. The identification of negative regulators of OB differentiation has prompted the use of anabolic agents. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from bone disease but also capitalizing on the resultant antitumor activity.

Original languageEnglish (US)
Pages (from-to)1278-1286
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number6
DOIs
StatePublished - Mar 15 2011
Externally publishedYes

Fingerprint

Bone Remodeling
Bone Diseases
Osteoclasts
Osteoblasts
Multiple Myeloma
Compression Fractures
Anabolic Agents
Spontaneous Fractures
Diphosphonates
Hypercalcemia
Standard of Care
Osteogenesis
Appointments and Schedules
Therapeutics
Bone Marrow
Quality of Life
Radiation
Cytokines
Morbidity
Pain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Advances in the biology and treatment of bone disease in multiple myeloma. / Raje, Noopur; Roodman, G. David.

In: Clinical Cancer Research, Vol. 17, No. 6, 15.03.2011, p. 1278-1286.

Research output: Contribution to journalArticle

@article{c28d8d7a4ea847969fec69e1bdb66f9c,
title = "Advances in the biology and treatment of bone disease in multiple myeloma",
abstract = "Osteolytic bone disease is pathognomonic of multiple myeloma (MM) and affects more than 80{\%} of patients. Bone disease results in skeletal-related events (SRE) such as vertebral compression fractures, which may cause cord compression, hypercalcemia, pathologic fractures that require radiation or surgical fixation, and severe pain. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. Osteolytic disease is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Bisphosphonates are a well-established treatment of myeloma-related skeletal disease and are the current standard of care. However, complications arising from their long-term use have prompted studies of schedule optimization and alternate strategies. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition. The identification of negative regulators of OB differentiation has prompted the use of anabolic agents. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from bone disease but also capitalizing on the resultant antitumor activity.",
author = "Noopur Raje and Roodman, {G. David}",
year = "2011",
month = "3",
day = "15",
doi = "10.1158/1078-0432.CCR-10-1804",
language = "English (US)",
volume = "17",
pages = "1278--1286",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Advances in the biology and treatment of bone disease in multiple myeloma

AU - Raje, Noopur

AU - Roodman, G. David

PY - 2011/3/15

Y1 - 2011/3/15

N2 - Osteolytic bone disease is pathognomonic of multiple myeloma (MM) and affects more than 80% of patients. Bone disease results in skeletal-related events (SRE) such as vertebral compression fractures, which may cause cord compression, hypercalcemia, pathologic fractures that require radiation or surgical fixation, and severe pain. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. Osteolytic disease is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Bisphosphonates are a well-established treatment of myeloma-related skeletal disease and are the current standard of care. However, complications arising from their long-term use have prompted studies of schedule optimization and alternate strategies. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition. The identification of negative regulators of OB differentiation has prompted the use of anabolic agents. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from bone disease but also capitalizing on the resultant antitumor activity.

AB - Osteolytic bone disease is pathognomonic of multiple myeloma (MM) and affects more than 80% of patients. Bone disease results in skeletal-related events (SRE) such as vertebral compression fractures, which may cause cord compression, hypercalcemia, pathologic fractures that require radiation or surgical fixation, and severe pain. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. Osteolytic disease is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Bisphosphonates are a well-established treatment of myeloma-related skeletal disease and are the current standard of care. However, complications arising from their long-term use have prompted studies of schedule optimization and alternate strategies. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition. The identification of negative regulators of OB differentiation has prompted the use of anabolic agents. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from bone disease but also capitalizing on the resultant antitumor activity.

UR - http://www.scopus.com/inward/record.url?scp=79952721484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952721484&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-10-1804

DO - 10.1158/1078-0432.CCR-10-1804

M3 - Article

C2 - 21411443

AN - SCOPUS:79952721484

VL - 17

SP - 1278

EP - 1286

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 6

ER -