The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice

Susanta K. Hui; Gregory R. Fairchild; Louis S. Kidder; Manju Sharma; Maryka Bhattacharya; Scott Jackson; Chap Le; Anna Petryk; Mohammad Saiful Islam; Douglas Yee

doi:10.1007/s00223-012-9688-0

The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice

Susanta K. Hui, Gregory R. Fairchild, Louis S. Kidder, Manju Sharma, Maryka Bhattacharya, Scott Jackson, Chap Le, Anna Petryk, Mohammad Saiful Islam, Douglas Yee

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Abstract

Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi ⁴⁵Ca. Thirty days post-⁴⁵Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of ⁴⁵Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal ⁴⁵Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via ⁴⁵Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar ⁴⁵Ca excretion but different bone microarchitectural responses. The ⁴⁵Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

Original language	English (US)
Pages (from-to)	372-384
Number of pages	13
Journal	Calcified Tissue International
Volume	92
Issue number	4
DOIs	https://doi.org/10.1007/s00223-012-9688-0
State	Published - Apr 2013

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (grants 1R03AR055333-01A1 and 1K12-HD055887-01) and by the PHS Cancer Center Support (grant P30 CA77398) and the Joseph E. Wargo cancer research fund from the University of Minnesota. S. K. H. is a scholar of the Building Interdisciplinary Careers in Women’s Health program. The authors acknowledge and thank the University of Minnesota – University Imaging Center, for aid in UV microscopy and Luke Arentsen, Kathleen Coghill, and Eftu Boru for laboratory assistance as well as Rajaram Gopalakrishnan, Kim Mansky, and Seymor Levitt for fruitful discussion pertaining to this experiment and report.

Keywords

Biodistribution
Bone remodeling
Ca
Ca surrogate
Clinically relevant radiation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice",

abstract = "Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar 45Ca excretion but different bone microarchitectural responses. The 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.",

keywords = "Biodistribution, Bone remodeling, Ca, Ca surrogate, Clinically relevant radiation",

author = "Hui, {Susanta K.} and Fairchild, {Gregory R.} and Kidder, {Louis S.} and Manju Sharma and Maryka Bhattacharya and Scott Jackson and Chap Le and Anna Petryk and Islam, {Mohammad Saiful} and Douglas Yee",

note = "Funding Information: This work was supported by the National Institutes of Health (grants 1R03AR055333-01A1 and 1K12-HD055887-01) and by the PHS Cancer Center Support (grant P30 CA77398) and the Joseph E. Wargo cancer research fund from the University of Minnesota. S. K. H. is a scholar of the Building Interdisciplinary Careers in Women{\textquoteright}s Health program. The authors acknowledge and thank the University of Minnesota – University Imaging Center, for aid in UV microscopy and Luke Arentsen, Kathleen Coghill, and Eftu Boru for laboratory assistance as well as Rajaram Gopalakrishnan, Kim Mansky, and Seymor Levitt for fruitful discussion pertaining to this experiment and report. ",

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T1 - The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice

AU - Hui, Susanta K.

AU - Fairchild, Gregory R.

AU - Kidder, Louis S.

AU - Sharma, Manju

AU - Bhattacharya, Maryka

AU - Jackson, Scott

AU - Le, Chap

AU - Petryk, Anna

AU - Islam, Mohammad Saiful

AU - Yee, Douglas

N1 - Funding Information: This work was supported by the National Institutes of Health (grants 1R03AR055333-01A1 and 1K12-HD055887-01) and by the PHS Cancer Center Support (grant P30 CA77398) and the Joseph E. Wargo cancer research fund from the University of Minnesota. S. K. H. is a scholar of the Building Interdisciplinary Careers in Women’s Health program. The authors acknowledge and thank the University of Minnesota – University Imaging Center, for aid in UV microscopy and Luke Arentsen, Kathleen Coghill, and Eftu Boru for laboratory assistance as well as Rajaram Gopalakrishnan, Kim Mansky, and Seymor Levitt for fruitful discussion pertaining to this experiment and report.

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N2 - Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar 45Ca excretion but different bone microarchitectural responses. The 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

AB - Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar 45Ca excretion but different bone microarchitectural responses. The 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

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KW - Ca surrogate

KW - Clinically relevant radiation

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The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice

Abstract

Bibliographical note

Keywords

UN SDGs

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