Effect of osteoporosis treatment agents on the cortical bone osteocyte microenvironment in adult estrogen-deficient, osteopenic rats

Amber Rath Stern, Xiaomei Yao, Yong Wang, Amanuel Berhe, Mark Dallas, Mark L. Johnson, Wei Yao, Donald B. Kimmel, Nancy E Lane

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Though osteoporosis is a significant cause of disability worldwide, treatment with pharmacologic agents decreases risk of fragility fracture. Though these treatments act through the bone remodeling system to improve bone mass, it is unclear if they alter the response of bone to mechanical loading at the level of the osteocyte. This pre-clinical study determined the relationship between microstructural bone tissue properties and osteocyte lacunar size and density to strain around osteocytes with standard osteoporosis treatment or sequential therapies. Six-month-old female ovariectomized (OVX) Sprague-Dawley rats were cycled through various sequences of pharmacological treatments [alendronate (Aln), raloxifene (Ral) and human parathyroid hormone-1,34 (PTH)] for three month intervals, over nine months. Linear nanoindentation mapping was used to determine Young's modulus in perilacunar and bone matrix regions around cortical bone osteocyte lacunae. Measurements of lacunar diameter and density were completed. Treatment-related differences in Young's modulus in the perilacunar and bone matrix regions were not observed. We confirmed previous data that showed that the bone matrix region was stiffer than the perilacunar matrix region. Whole bone material properties were correlated to perilacunar matrix stiffness. Finite element models predicted a range of mechanical strain amplification factors estimated at the osteocyte across treatment groups. In summary, though the perilacunar matrix near cortical osteocyte lacuna is not as stiff as bone matrix further away, osteoporosis treatment agents do not affect the stiffness of bone tissue near osteocyte lacunae.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalBone Reports
Volume8
DOIs
StatePublished - Jun 1 2018

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Osteocytes
Osteoporosis
Estrogens
Bone Matrix
Bone and Bones
Elastic Modulus
Teriparatide
Alendronate
Bone Remodeling
Cortical Bone
Sprague Dawley Rats
Pharmacology

Keywords

  • Alendronate
  • Finite element model
  • Lacuna
  • Nanoindentation
  • PTH(1-34)
  • Raloxifene
  • Sequential treatment

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Effect of osteoporosis treatment agents on the cortical bone osteocyte microenvironment in adult estrogen-deficient, osteopenic rats. / Stern, Amber Rath; Yao, Xiaomei; Wang, Yong; Berhe, Amanuel; Dallas, Mark; Johnson, Mark L.; Yao, Wei; Kimmel, Donald B.; Lane, Nancy E.

In: Bone Reports, Vol. 8, 01.06.2018, p. 115-124.

Research output: Contribution to journalArticle

Stern, Amber Rath ; Yao, Xiaomei ; Wang, Yong ; Berhe, Amanuel ; Dallas, Mark ; Johnson, Mark L. ; Yao, Wei ; Kimmel, Donald B. ; Lane, Nancy E. / Effect of osteoporosis treatment agents on the cortical bone osteocyte microenvironment in adult estrogen-deficient, osteopenic rats. In: Bone Reports. 2018 ; Vol. 8. pp. 115-124.
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AB - Though osteoporosis is a significant cause of disability worldwide, treatment with pharmacologic agents decreases risk of fragility fracture. Though these treatments act through the bone remodeling system to improve bone mass, it is unclear if they alter the response of bone to mechanical loading at the level of the osteocyte. This pre-clinical study determined the relationship between microstructural bone tissue properties and osteocyte lacunar size and density to strain around osteocytes with standard osteoporosis treatment or sequential therapies. Six-month-old female ovariectomized (OVX) Sprague-Dawley rats were cycled through various sequences of pharmacological treatments [alendronate (Aln), raloxifene (Ral) and human parathyroid hormone-1,34 (PTH)] for three month intervals, over nine months. Linear nanoindentation mapping was used to determine Young's modulus in perilacunar and bone matrix regions around cortical bone osteocyte lacunae. Measurements of lacunar diameter and density were completed. Treatment-related differences in Young's modulus in the perilacunar and bone matrix regions were not observed. We confirmed previous data that showed that the bone matrix region was stiffer than the perilacunar matrix region. Whole bone material properties were correlated to perilacunar matrix stiffness. Finite element models predicted a range of mechanical strain amplification factors estimated at the osteocyte across treatment groups. In summary, though the perilacunar matrix near cortical osteocyte lacuna is not as stiff as bone matrix further away, osteoporosis treatment agents do not affect the stiffness of bone tissue near osteocyte lacunae.

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