Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats

Emily E Hohman, Joanna K Hodges, Meryl E Wastney, Pamela J Lachcik, Chun-Ya Han, Denise Dwyer, Munro Peacock, Paul J Kostenuik, Connie M Weaver

Research output: Contribution to journalArticle

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Abstract

Serum calcium (Ca) is maintained in a narrow range through regulation of Ca metabolism in the intestine, kidney, and bone. Calcium is incorporated and resorbed from bone during bone remodeling via cellular processes as well as by exchange. Both routes contribute to calcium homeostasis. To assess the magnitude of bone turnover contribution to calcium homeostasis we labeled bone with a Ca tracer and measured Ca release following stimulation or suppression of bone resorption. Young growing male rats (n = 162) were dosed with 45Ca to label skeletal Ca. After a one-month period to allow the label to incorporate into the skeleton, rats were treated with a bone resorption antagonist (OPG), a bone resorption agonist (RANKL), or vehicle control (PBS). Serum and urine 45Ca and total Ca, and serum TRACP5b (a bone resorption biomarker), were monitored for 45 days following treatment. Tracer data were analyzed by a compartmental model using WinSAAM to quantify dynamic changes in Ca metabolism and identify sites of change following treatment. In RANKL treated rats, both serum 45Ca and serum TRACP5b were increased by >70% due to a 25-fold increase in bone resorption. In OPG treated rats, both serum 45Ca and serum TRACP5b were suppressed by >70% due to a 75% decrease in bone resorption, a 3-fold increase in bone formation, and a 50% increase in absorption. Because TRACP5b and 45Ca responded similarly, we conclude that Ca release from bone into serum occurs mostly via osteoclast-mediated bone resorption. However, because serum Ca concentration did not change with altered resorption in response to either RANKL or OPG treatment, we also conclude that serum Ca concentration under normal dietary conditions in young growing male rats is maintained by processes in addition to cellular bone resorption.

Original languageEnglish (US)
Pages (from-to)162-170
Number of pages9
JournalBone
Volume116
DOIs
StateE-pub ahead of print - Aug 2 2018
Externally publishedYes

Fingerprint

Osteoprotegerin
Bone Resorption
Calcium
Serum
Bone and Bones
Bone Remodeling
Homeostasis
Osteoclasts
Osteogenesis
Skeleton
Intestines

Cite this

Hohman, Emily E ; Hodges, Joanna K ; Wastney, Meryl E ; Lachcik, Pamela J ; Han, Chun-Ya ; Dwyer, Denise ; Peacock, Munro ; Kostenuik, Paul J ; Weaver, Connie M. / Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats. In: Bone. 2018 ; Vol. 116. pp. 162-170.
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title = "Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats",
abstract = "Serum calcium (Ca) is maintained in a narrow range through regulation of Ca metabolism in the intestine, kidney, and bone. Calcium is incorporated and resorbed from bone during bone remodeling via cellular processes as well as by exchange. Both routes contribute to calcium homeostasis. To assess the magnitude of bone turnover contribution to calcium homeostasis we labeled bone with a Ca tracer and measured Ca release following stimulation or suppression of bone resorption. Young growing male rats (n = 162) were dosed with 45Ca to label skeletal Ca. After a one-month period to allow the label to incorporate into the skeleton, rats were treated with a bone resorption antagonist (OPG), a bone resorption agonist (RANKL), or vehicle control (PBS). Serum and urine 45Ca and total Ca, and serum TRACP5b (a bone resorption biomarker), were monitored for 45 days following treatment. Tracer data were analyzed by a compartmental model using WinSAAM to quantify dynamic changes in Ca metabolism and identify sites of change following treatment. In RANKL treated rats, both serum 45Ca and serum TRACP5b were increased by >70{\%} due to a 25-fold increase in bone resorption. In OPG treated rats, both serum 45Ca and serum TRACP5b were suppressed by >70{\%} due to a 75{\%} decrease in bone resorption, a 3-fold increase in bone formation, and a 50{\%} increase in absorption. Because TRACP5b and 45Ca responded similarly, we conclude that Ca release from bone into serum occurs mostly via osteoclast-mediated bone resorption. However, because serum Ca concentration did not change with altered resorption in response to either RANKL or OPG treatment, we also conclude that serum Ca concentration under normal dietary conditions in young growing male rats is maintained by processes in addition to cellular bone resorption.",
author = "Hohman, {Emily E} and Hodges, {Joanna K} and Wastney, {Meryl E} and Lachcik, {Pamela J} and Chun-Ya Han and Denise Dwyer and Munro Peacock and Kostenuik, {Paul J} and Weaver, {Connie M}",
note = "Copyright {\circledC} 2018. Published by Elsevier Inc.",
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doi = "10.1016/j.bone.2018.08.001",
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Hohman, EE, Hodges, JK, Wastney, ME, Lachcik, PJ, Han, C-Y, Dwyer, D, Peacock, M, Kostenuik, PJ & Weaver, CM 2018, 'Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats', Bone, vol. 116, pp. 162-170. https://doi.org/10.1016/j.bone.2018.08.001

Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats. / Hohman, Emily E; Hodges, Joanna K; Wastney, Meryl E; Lachcik, Pamela J; Han, Chun-Ya; Dwyer, Denise; Peacock, Munro; Kostenuik, Paul J; Weaver, Connie M.

In: Bone, Vol. 116, 02.08.2018, p. 162-170.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serum calcium concentration is maintained when bone resorption is suppressed by osteoprotegerin in young growing male rats

AU - Hohman, Emily E

AU - Hodges, Joanna K

AU - Wastney, Meryl E

AU - Lachcik, Pamela J

AU - Han, Chun-Ya

AU - Dwyer, Denise

AU - Peacock, Munro

AU - Kostenuik, Paul J

AU - Weaver, Connie M

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2018/8/2

Y1 - 2018/8/2

N2 - Serum calcium (Ca) is maintained in a narrow range through regulation of Ca metabolism in the intestine, kidney, and bone. Calcium is incorporated and resorbed from bone during bone remodeling via cellular processes as well as by exchange. Both routes contribute to calcium homeostasis. To assess the magnitude of bone turnover contribution to calcium homeostasis we labeled bone with a Ca tracer and measured Ca release following stimulation or suppression of bone resorption. Young growing male rats (n = 162) were dosed with 45Ca to label skeletal Ca. After a one-month period to allow the label to incorporate into the skeleton, rats were treated with a bone resorption antagonist (OPG), a bone resorption agonist (RANKL), or vehicle control (PBS). Serum and urine 45Ca and total Ca, and serum TRACP5b (a bone resorption biomarker), were monitored for 45 days following treatment. Tracer data were analyzed by a compartmental model using WinSAAM to quantify dynamic changes in Ca metabolism and identify sites of change following treatment. In RANKL treated rats, both serum 45Ca and serum TRACP5b were increased by >70% due to a 25-fold increase in bone resorption. In OPG treated rats, both serum 45Ca and serum TRACP5b were suppressed by >70% due to a 75% decrease in bone resorption, a 3-fold increase in bone formation, and a 50% increase in absorption. Because TRACP5b and 45Ca responded similarly, we conclude that Ca release from bone into serum occurs mostly via osteoclast-mediated bone resorption. However, because serum Ca concentration did not change with altered resorption in response to either RANKL or OPG treatment, we also conclude that serum Ca concentration under normal dietary conditions in young growing male rats is maintained by processes in addition to cellular bone resorption.

AB - Serum calcium (Ca) is maintained in a narrow range through regulation of Ca metabolism in the intestine, kidney, and bone. Calcium is incorporated and resorbed from bone during bone remodeling via cellular processes as well as by exchange. Both routes contribute to calcium homeostasis. To assess the magnitude of bone turnover contribution to calcium homeostasis we labeled bone with a Ca tracer and measured Ca release following stimulation or suppression of bone resorption. Young growing male rats (n = 162) were dosed with 45Ca to label skeletal Ca. After a one-month period to allow the label to incorporate into the skeleton, rats were treated with a bone resorption antagonist (OPG), a bone resorption agonist (RANKL), or vehicle control (PBS). Serum and urine 45Ca and total Ca, and serum TRACP5b (a bone resorption biomarker), were monitored for 45 days following treatment. Tracer data were analyzed by a compartmental model using WinSAAM to quantify dynamic changes in Ca metabolism and identify sites of change following treatment. In RANKL treated rats, both serum 45Ca and serum TRACP5b were increased by >70% due to a 25-fold increase in bone resorption. In OPG treated rats, both serum 45Ca and serum TRACP5b were suppressed by >70% due to a 75% decrease in bone resorption, a 3-fold increase in bone formation, and a 50% increase in absorption. Because TRACP5b and 45Ca responded similarly, we conclude that Ca release from bone into serum occurs mostly via osteoclast-mediated bone resorption. However, because serum Ca concentration did not change with altered resorption in response to either RANKL or OPG treatment, we also conclude that serum Ca concentration under normal dietary conditions in young growing male rats is maintained by processes in addition to cellular bone resorption.

U2 - 10.1016/j.bone.2018.08.001

DO - 10.1016/j.bone.2018.08.001

M3 - Article

C2 - 30077758

VL - 116

SP - 162

EP - 170

JO - Bone

JF - Bone

SN - 8756-3282

ER -