Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity

Nancy E Lane, Geetha Mohan, Wei Yao, Kie Shidara, Yu An Evan Lay, Junjing Jia, Alanna Dubrovsky, Donald B. Kimmel

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalBone Reports
Volume9
DOIs
StatePublished - Dec 1 2018

Fingerprint

Osteonecrosis
Glucocorticoids
Bone and Bones
Thigh
Therapeutics
Epiphyses

Keywords

  • Dexamethasone
  • Distal femoral epiphysis
  • hPTH (1–34)
  • LLP2A-Ale
  • Prevention

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity. / Lane, Nancy E; Mohan, Geetha; Yao, Wei; Shidara, Kie; Lay, Yu An Evan; Jia, Junjing; Dubrovsky, Alanna; Kimmel, Donald B.

In: Bone Reports, Vol. 9, 01.12.2018, p. 181-187.

Research output: Contribution to journalArticle

Lane, Nancy E ; Mohan, Geetha ; Yao, Wei ; Shidara, Kie ; Lay, Yu An Evan ; Jia, Junjing ; Dubrovsky, Alanna ; Kimmel, Donald B. / Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity. In: Bone Reports. 2018 ; Vol. 9. pp. 181-187.
@article{6e9c2b9c3daa4c51a5b03112ea22171b,
title = "Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity",
abstract = "Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14{\%} in the Con group and 36{\%} in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice.",
keywords = "Dexamethasone, Distal femoral epiphysis, hPTH (1–34), LLP2A-Ale, Prevention",
author = "Lane, {Nancy E} and Geetha Mohan and Wei Yao and Kie Shidara and Lay, {Yu An Evan} and Junjing Jia and Alanna Dubrovsky and Kimmel, {Donald B.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.bonr.2018.10.003",
language = "English (US)",
volume = "9",
pages = "181--187",
journal = "Bone Reports",
issn = "2352-1872",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity

AU - Lane, Nancy E

AU - Mohan, Geetha

AU - Yao, Wei

AU - Shidara, Kie

AU - Lay, Yu An Evan

AU - Jia, Junjing

AU - Dubrovsky, Alanna

AU - Kimmel, Donald B.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice.

AB - Objective: Determine if LLP2A-Ale or PTH (1–34) affects the prevalence of glucocorticoid-induced osteonecrosis (ON) in a mouse model. Methods: Eight-week-old young adult male BALB/cJ mice were weight-randomized into Control (Con), glucocorticoid (GC)-only, or concurrent treatments with GC and LLP2A-Ale (250 μg/kg or 500 μg/kg, IV, Days 1, 14, 28) or parathyroid hormone hPTH (1–34) (40 μg/kg, 5×/week). Mice were necropsied after 45 days for qualitative evaluation of prevalent ON and quantitative evaluation of vascularity in the distal femoral epiphysis (DFE); and quantitative evaluation of bone mass, microarchitecture, and strength in the distal femoral metaphysis and lumbar vertebral body. Results: The prevalence of ON was 14% in the Con group and 36% in the GC-only group (P = 0.07). The prevalence of ON did not differ among GC-only, GC + LLP2A-Ale, and GC + PTH groups. GC-only mice had significantly lower trabecular and cortical bone strength than Con, while GC + LLP2A-Ale (500 μg/kg) and GC + PTH (1–34) groups had significantly greater trabecular bone strength than the GC-only group. GC + LLP2A-Ale (250 μg/kg and 500 μg/kg) and GC + PTH had significantly higher trabecular bone volume than GC-only mice at the vertebrae, distal femoral epiphyses and distal femoral metaphyses. DFE vascularity was lower in GC-only mice than in all other groups. Conclusion: Neither LLP2A-Ale nor hPTH (1–34) reduced the prevalence of GC-induced ON, compared to GC-only mice. However, GC-treated mice given LLP2A-Ale or hPTH (1–34) had better bone mass, microarchitecture, and strength in trabecular-rich regions, and higher levels of vascularity than GC-only mice.

KW - Dexamethasone

KW - Distal femoral epiphysis

KW - hPTH (1–34)

KW - LLP2A-Ale

KW - Prevention

UR - http://www.scopus.com/inward/record.url?scp=85056875523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056875523&partnerID=8YFLogxK

U2 - 10.1016/j.bonr.2018.10.003

DO - 10.1016/j.bonr.2018.10.003

M3 - Article

VL - 9

SP - 181

EP - 187

JO - Bone Reports

JF - Bone Reports

SN - 2352-1872

ER -