Strain-specific differences in the development of bone loss and incidence of osteonecrosis following glucocorticoid treatment in two different mouse strains

Kie Shidara, Geetha Mohan, Yan An Evan Lay, Karl J. Jepsen, Wei Yao, Nancy E Lane

Research output: Contribution to journalArticle

Abstract

Objective: Glucocorticoids (GCs) are commonly prescribed as treatment for chronic inflammatory diseases. Prolonged use of GCs is a common cause of atraumatic osteonecrosis (ON) and secondary osteoporosis. Currently, there is no effective treatment for this disease; therefore, a reliable animal model would be useful to study both the pathology and novel treatment strategies for patients with the disease. The aim of this study was to establish a validated, reproducible model of GC-induced ON and bone loss in two different mouse strains (BALB/c and C57BL/6). Methods: Seven-week-old male BALB/c (n = 32) and male C57BL/6 mice (n = 32) were randomised into placebo or GC groups and treated with daily 4 mg/L oral dexamethasone in drinking water for 90 days. Study outcome measures included histologic assessment of ON of the distal femur, bone mass and mechanical strength of tibia and lumbar vertebral body, osteoclast number, biochemical measure of bone formation and bone marrow fat quantitation. Results: GC-induced ON lesions were observed in the distal femur in 47% of the male BALB/c mice and 25% of the male C57BL/6 mice. GC treatment decreased the trabecular bone volume and serum pro-collagen type 1N-protease (P1NP) in BALB/c mice compared with the placebo (p < 0.05) and reduced tibial bone strength in both BALB/c and C57BL/6 mice. GC-treated BALB/c mice had significantly greater marrow fat levels compared to the placebo group. Conclusion: GC-induced ON was more prevalent in the male BALB/c mice compared to the male C57BL/6 mice. GC treatment significantly reduced bone mass, bone formation measured by P1NP, bone strength and increased marrow fat levels in male BALB/c mice. Therefore, the use of male BALB/c mice strain is recommended for both diagnostic and therapeutic studies for the prevention and treatment of ON and bone loss following prolonged treatment with GCs. The Translational Potential of this Article: GCs are commonly used to treat patients with various chronic inflammatory diseases, and this is associated with both the development of ON and bone loss. Our study confirmed that the BALB/c mouse strain treated for 90 days with GC may be useful for developing novel treatments for ON.

Original languageEnglish (US)
JournalJournal of Orthopaedic Translation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Osteonecrosis
Bone Development
Glucocorticoids
Incidence
Bone and Bones
Inbred C57BL Mouse
Therapeutics
Bone Marrow
Fats
Placebos
Osteogenesis
Femur
Peptide Hydrolases
Chronic Disease
Collagen
Osteoclasts
Tibia
Drinking Water
Dexamethasone
Osteoporosis

Keywords

  • Animal model
  • Bone loss
  • Glucocorticoids
  • Osteonecrosis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

@article{f105427218904e6fa742359cac560327,
title = "Strain-specific differences in the development of bone loss and incidence of osteonecrosis following glucocorticoid treatment in two different mouse strains",
abstract = "Objective: Glucocorticoids (GCs) are commonly prescribed as treatment for chronic inflammatory diseases. Prolonged use of GCs is a common cause of atraumatic osteonecrosis (ON) and secondary osteoporosis. Currently, there is no effective treatment for this disease; therefore, a reliable animal model would be useful to study both the pathology and novel treatment strategies for patients with the disease. The aim of this study was to establish a validated, reproducible model of GC-induced ON and bone loss in two different mouse strains (BALB/c and C57BL/6). Methods: Seven-week-old male BALB/c (n = 32) and male C57BL/6 mice (n = 32) were randomised into placebo or GC groups and treated with daily 4 mg/L oral dexamethasone in drinking water for 90 days. Study outcome measures included histologic assessment of ON of the distal femur, bone mass and mechanical strength of tibia and lumbar vertebral body, osteoclast number, biochemical measure of bone formation and bone marrow fat quantitation. Results: GC-induced ON lesions were observed in the distal femur in 47{\%} of the male BALB/c mice and 25{\%} of the male C57BL/6 mice. GC treatment decreased the trabecular bone volume and serum pro-collagen type 1N-protease (P1NP) in BALB/c mice compared with the placebo (p < 0.05) and reduced tibial bone strength in both BALB/c and C57BL/6 mice. GC-treated BALB/c mice had significantly greater marrow fat levels compared to the placebo group. Conclusion: GC-induced ON was more prevalent in the male BALB/c mice compared to the male C57BL/6 mice. GC treatment significantly reduced bone mass, bone formation measured by P1NP, bone strength and increased marrow fat levels in male BALB/c mice. Therefore, the use of male BALB/c mice strain is recommended for both diagnostic and therapeutic studies for the prevention and treatment of ON and bone loss following prolonged treatment with GCs. The Translational Potential of this Article: GCs are commonly used to treat patients with various chronic inflammatory diseases, and this is associated with both the development of ON and bone loss. Our study confirmed that the BALB/c mouse strain treated for 90 days with GC may be useful for developing novel treatments for ON.",
keywords = "Animal model, Bone loss, Glucocorticoids, Osteonecrosis",
author = "Kie Shidara and Geetha Mohan and {Evan Lay}, {Yan An} and Jepsen, {Karl J.} and Wei Yao and Lane, {Nancy E}",
year = "2018",
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day = "1",
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language = "English (US)",
journal = "Journal of Orthopaedic Translation",
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TY - JOUR

T1 - Strain-specific differences in the development of bone loss and incidence of osteonecrosis following glucocorticoid treatment in two different mouse strains

AU - Shidara, Kie

AU - Mohan, Geetha

AU - Evan Lay, Yan An

AU - Jepsen, Karl J.

AU - Yao, Wei

AU - Lane, Nancy E

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: Glucocorticoids (GCs) are commonly prescribed as treatment for chronic inflammatory diseases. Prolonged use of GCs is a common cause of atraumatic osteonecrosis (ON) and secondary osteoporosis. Currently, there is no effective treatment for this disease; therefore, a reliable animal model would be useful to study both the pathology and novel treatment strategies for patients with the disease. The aim of this study was to establish a validated, reproducible model of GC-induced ON and bone loss in two different mouse strains (BALB/c and C57BL/6). Methods: Seven-week-old male BALB/c (n = 32) and male C57BL/6 mice (n = 32) were randomised into placebo or GC groups and treated with daily 4 mg/L oral dexamethasone in drinking water for 90 days. Study outcome measures included histologic assessment of ON of the distal femur, bone mass and mechanical strength of tibia and lumbar vertebral body, osteoclast number, biochemical measure of bone formation and bone marrow fat quantitation. Results: GC-induced ON lesions were observed in the distal femur in 47% of the male BALB/c mice and 25% of the male C57BL/6 mice. GC treatment decreased the trabecular bone volume and serum pro-collagen type 1N-protease (P1NP) in BALB/c mice compared with the placebo (p < 0.05) and reduced tibial bone strength in both BALB/c and C57BL/6 mice. GC-treated BALB/c mice had significantly greater marrow fat levels compared to the placebo group. Conclusion: GC-induced ON was more prevalent in the male BALB/c mice compared to the male C57BL/6 mice. GC treatment significantly reduced bone mass, bone formation measured by P1NP, bone strength and increased marrow fat levels in male BALB/c mice. Therefore, the use of male BALB/c mice strain is recommended for both diagnostic and therapeutic studies for the prevention and treatment of ON and bone loss following prolonged treatment with GCs. The Translational Potential of this Article: GCs are commonly used to treat patients with various chronic inflammatory diseases, and this is associated with both the development of ON and bone loss. Our study confirmed that the BALB/c mouse strain treated for 90 days with GC may be useful for developing novel treatments for ON.

AB - Objective: Glucocorticoids (GCs) are commonly prescribed as treatment for chronic inflammatory diseases. Prolonged use of GCs is a common cause of atraumatic osteonecrosis (ON) and secondary osteoporosis. Currently, there is no effective treatment for this disease; therefore, a reliable animal model would be useful to study both the pathology and novel treatment strategies for patients with the disease. The aim of this study was to establish a validated, reproducible model of GC-induced ON and bone loss in two different mouse strains (BALB/c and C57BL/6). Methods: Seven-week-old male BALB/c (n = 32) and male C57BL/6 mice (n = 32) were randomised into placebo or GC groups and treated with daily 4 mg/L oral dexamethasone in drinking water for 90 days. Study outcome measures included histologic assessment of ON of the distal femur, bone mass and mechanical strength of tibia and lumbar vertebral body, osteoclast number, biochemical measure of bone formation and bone marrow fat quantitation. Results: GC-induced ON lesions were observed in the distal femur in 47% of the male BALB/c mice and 25% of the male C57BL/6 mice. GC treatment decreased the trabecular bone volume and serum pro-collagen type 1N-protease (P1NP) in BALB/c mice compared with the placebo (p < 0.05) and reduced tibial bone strength in both BALB/c and C57BL/6 mice. GC-treated BALB/c mice had significantly greater marrow fat levels compared to the placebo group. Conclusion: GC-induced ON was more prevalent in the male BALB/c mice compared to the male C57BL/6 mice. GC treatment significantly reduced bone mass, bone formation measured by P1NP, bone strength and increased marrow fat levels in male BALB/c mice. Therefore, the use of male BALB/c mice strain is recommended for both diagnostic and therapeutic studies for the prevention and treatment of ON and bone loss following prolonged treatment with GCs. The Translational Potential of this Article: GCs are commonly used to treat patients with various chronic inflammatory diseases, and this is associated with both the development of ON and bone loss. Our study confirmed that the BALB/c mouse strain treated for 90 days with GC may be useful for developing novel treatments for ON.

KW - Animal model

KW - Bone loss

KW - Glucocorticoids

KW - Osteonecrosis

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