An in vivo model of human multiple myeloma bone disease

M. Alsina, B. F. Boyce, G. R. Mundy, G. David Roodman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH- 77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin Gκ (IgGκ), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 106 ARH-77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers. Thus, we have developed a model of human MM bone disease which should be very useful to study the pathogenesis of the bone destruction in MM, and to develop novel therapeutic strategies to improve or arrest the bone disease in these patients.

Original languageEnglish (US)
Pages (from-to)48-50
Number of pages3
JournalStem Cells
Volume13
Issue numberSUPPL. 2
StatePublished - 1995
Externally publishedYes

Fingerprint

Bone Diseases
Multiple Myeloma
Hypercalcemia
Bone and Bones
Severe Combined Immunodeficiency
Osteoclasts
Plasma Cell Leukemia
X-Rays
Spontaneous Fractures
Paralysis
Histology
Spine
Spleen
Extremities
Immunoglobulin G
Calcium
Morbidity
Cell Line
Control Groups
Injections

Keywords

  • Bone disease
  • Multiple myeloma
  • Osteoblast
  • Osteoclast

ASJC Scopus subject areas

  • Cell Biology

Cite this

Alsina, M., Boyce, B. F., Mundy, G. R., & Roodman, G. D. (1995). An in vivo model of human multiple myeloma bone disease. Stem Cells, 13(SUPPL. 2), 48-50.

An in vivo model of human multiple myeloma bone disease. / Alsina, M.; Boyce, B. F.; Mundy, G. R.; Roodman, G. David.

In: Stem Cells, Vol. 13, No. SUPPL. 2, 1995, p. 48-50.

Research output: Contribution to journalArticle

Alsina, M, Boyce, BF, Mundy, GR & Roodman, GD 1995, 'An in vivo model of human multiple myeloma bone disease', Stem Cells, vol. 13, no. SUPPL. 2, pp. 48-50.
Alsina M, Boyce BF, Mundy GR, Roodman GD. An in vivo model of human multiple myeloma bone disease. Stem Cells. 1995;13(SUPPL. 2):48-50.
Alsina, M. ; Boyce, B. F. ; Mundy, G. R. ; Roodman, G. David. / An in vivo model of human multiple myeloma bone disease. In: Stem Cells. 1995 ; Vol. 13, No. SUPPL. 2. pp. 48-50.
@article{e0b8501d8d404a2dbc39c37d4bdb5ed1,
title = "An in vivo model of human multiple myeloma bone disease",
abstract = "Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH- 77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin Gκ (IgGκ), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 106 ARH-77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers. Thus, we have developed a model of human MM bone disease which should be very useful to study the pathogenesis of the bone destruction in MM, and to develop novel therapeutic strategies to improve or arrest the bone disease in these patients.",
keywords = "Bone disease, Multiple myeloma, Osteoblast, Osteoclast",
author = "M. Alsina and Boyce, {B. F.} and Mundy, {G. R.} and Roodman, {G. David}",
year = "1995",
language = "English (US)",
volume = "13",
pages = "48--50",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "SUPPL. 2",

}

TY - JOUR

T1 - An in vivo model of human multiple myeloma bone disease

AU - Alsina, M.

AU - Boyce, B. F.

AU - Mundy, G. R.

AU - Roodman, G. David

PY - 1995

Y1 - 1995

N2 - Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH- 77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin Gκ (IgGκ), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 106 ARH-77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers. Thus, we have developed a model of human MM bone disease which should be very useful to study the pathogenesis of the bone destruction in MM, and to develop novel therapeutic strategies to improve or arrest the bone disease in these patients.

AB - Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH- 77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin Gκ (IgGκ), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 106 ARH-77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers. Thus, we have developed a model of human MM bone disease which should be very useful to study the pathogenesis of the bone destruction in MM, and to develop novel therapeutic strategies to improve or arrest the bone disease in these patients.

KW - Bone disease

KW - Multiple myeloma

KW - Osteoblast

KW - Osteoclast

UR - http://www.scopus.com/inward/record.url?scp=0029129937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029129937&partnerID=8YFLogxK

M3 - Article

C2 - 8520511

AN - SCOPUS:0029129937

VL - 13

SP - 48

EP - 50

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - SUPPL. 2

ER -