Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma

Jose C. Cruz, Melissa Alsina, Fiona Craig, Toshiyuki Yoneda, Judith L. Anderson, Mark Dallas, G. David Roodman

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Objective. The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Materials and Methods. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. Results. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm2) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB.Conclusion. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.

Original languageEnglish (US)
Pages (from-to)441-447
Number of pages7
JournalExperimental Hematology
Volume29
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

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Bone Diseases
Bone Development
Osteoclasts
Paraplegia
Bone Marrow
Diphosphonates
Tumor Burden
Multiple Myeloma
SCID Mice
ibandronic acid
Subcutaneous Injections
Therapeutics
Neoplasms
Bone and Bones
Control Groups
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma. / Cruz, Jose C.; Alsina, Melissa; Craig, Fiona; Yoneda, Toshiyuki; Anderson, Judith L.; Dallas, Mark; Roodman, G. David.

In: Experimental Hematology, Vol. 29, No. 4, 2001, p. 441-447.

Research output: Contribution to journalArticle

Cruz, Jose C. ; Alsina, Melissa ; Craig, Fiona ; Yoneda, Toshiyuki ; Anderson, Judith L. ; Dallas, Mark ; Roodman, G. David. / Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma. In: Experimental Hematology. 2001 ; Vol. 29, No. 4. pp. 441-447.
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abstract = "Objective. The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Materials and Methods. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. Results. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm2) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB.Conclusion. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.",
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T1 - Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma

AU - Cruz, Jose C.

AU - Alsina, Melissa

AU - Craig, Fiona

AU - Yoneda, Toshiyuki

AU - Anderson, Judith L.

AU - Dallas, Mark

AU - Roodman, G. David

PY - 2001

Y1 - 2001

N2 - Objective. The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Materials and Methods. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. Results. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm2) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB.Conclusion. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.

AB - Objective. The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Materials and Methods. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. Results. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm2) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB.Conclusion. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.

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