μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy

Chantal M.J. de Bakker, Allison R. Altman, Wei Ju Tseng, Mary Beth Tribble, Connie Li, Abhishek Chandra, Ling Qin, X. Sherry Liu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r = 0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.

Original languageEnglish (US)
Pages (from-to)198-207
Number of pages10
JournalBone
Volume73
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Alendronate
Bone Resorption
Parathyroid Hormone
Osteogenesis
Bone and Bones
Bone Remodeling
Therapeutics
Histology
Anabolic Agents
Diphosphonates
Osteoclasts
Tibia
Pharmaceutical Preparations
Osteoporosis

Keywords

  • Animal models/rodent
  • Anti-resorptive treatment
  • Bone stiffness
  • In vivo μCT
  • Parathyroid hormone
  • Trabecular bone microstructure

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

Cite this

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy. / de Bakker, Chantal M.J.; Altman, Allison R.; Tseng, Wei Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X. Sherry.

In: Bone, Vol. 73, 01.04.2015, p. 198-207.

Research output: Contribution to journalArticle

de Bakker, Chantal M.J. ; Altman, Allison R. ; Tseng, Wei Ju ; Tribble, Mary Beth ; Li, Connie ; Chandra, Abhishek ; Qin, Ling ; Liu, X. Sherry. / μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy. In: Bone. 2015 ; Vol. 73. pp. 198-207.
@article{f00eee117a9c47a0974f27b7ed25fcc1,
title = "μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy",
abstract = "Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r = 0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.",
keywords = "Animal models/rodent, Anti-resorptive treatment, Bone stiffness, In vivo μCT, Parathyroid hormone, Trabecular bone microstructure",
author = "{de Bakker}, {Chantal M.J.} and Altman, {Allison R.} and Tseng, {Wei Ju} and Tribble, {Mary Beth} and Connie Li and Abhishek Chandra and Ling Qin and Liu, {X. Sherry}",
year = "2015",
month = "4",
day = "1",
doi = "10.1016/j.bone.2014.12.061",
language = "English (US)",
volume = "73",
pages = "198--207",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy

AU - de Bakker, Chantal M.J.

AU - Altman, Allison R.

AU - Tseng, Wei Ju

AU - Tribble, Mary Beth

AU - Li, Connie

AU - Chandra, Abhishek

AU - Qin, Ling

AU - Liu, X. Sherry

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r = 0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.

AB - Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r = 0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed.

KW - Animal models/rodent

KW - Anti-resorptive treatment

KW - Bone stiffness

KW - In vivo μCT

KW - Parathyroid hormone

KW - Trabecular bone microstructure

UR - http://www.scopus.com/inward/record.url?scp=84920973040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920973040&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2014.12.061

DO - 10.1016/j.bone.2014.12.061

M3 - Article

VL - 73

SP - 198

EP - 207

JO - Bone

JF - Bone

SN - 8756-3282

ER -