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, Jia Junjing, Alanna Dubrovsky, Donald B. Kimmel

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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
StatePublished - Dec 1 2018


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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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