Liraglutide increases bone formation and inhibits bone resorption in rats with glucocorticoid-induced osteoporosis

J Endocrinol Invest. 2019 Sep;42(9):1125-1131. doi: 10.1007/s40618-019-01034-5. Epub 2019 Apr 6.

Abstract

Objective: This study aimed to investigate the effects of liraglutide on bone metabolism markers in rat models with glucocorticoid-induced osteoporosis (GIOP), including the effects on bone mass, bone tissue microstructure, bone biomechanics, and bone turnover markers.

Method: Thirty male Sprague-Dawley rats aged 8 weeks were randomly divided into three groups: the control group (n = 10) was intramuscularly injected with an equal volume of 0.9% sodium chloride, the dexamethasone group (n = 10) was intramuscularly injected with dexamethasone at 1 mg/kg (twice a week) to induce GIOP, the dexamethasone plus liraglutide group (n = 10) was subcutaneously injected with liraglutide at 200 μg/kg daily, simultaneously. The bilateral femurs and the fifth lumbar vertebrae were collected after 12 weeks to perform micro-computed tomography and bone biomechanical examinations. Also, tartrate-resistant acid phosphatase (TRACP), cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), alkaline phosphatase (ALP), and osteocalcin (OC) were tested.

Results: The bone mineral density (BMD), bone microstructure, and bone biomechanical markers reduced significantly in the dexamethasone group compared with the control group. The bone resorption indicators (TRACP and CTX-I) increased, while the bone formation indicators (ALP and OC) decreased. After liraglutide treatment, BMD, bone microstructure, and bone biomechanical markers improved significantly. Moreover, TRACP and CTX-I decreased significantly, while ALP and OC increased compared with the dexamethasone group.

Conclusions: Liraglutide improved BMD, bone microstructure, and bone strength and reversed GIOP, primarily through the reduction of bone resorption and promotion of bone formation.

Keywords: Bone biomechanics; Glucocorticoid-induced osteoporosis; Liraglutide; Micro-CT.

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Bone Density / drug effects
  • Bone Resorption / chemically induced
  • Bone Resorption / prevention & control*
  • Glucocorticoids / adverse effects*
  • Hypoglycemic Agents / pharmacology*
  • Liraglutide / pharmacology*
  • Male
  • Osteogenesis / drug effects*
  • Osteoporosis / chemically induced
  • Osteoporosis / drug therapy*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Glucocorticoids
  • Hypoglycemic Agents
  • Liraglutide