Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice

J Clin Invest. 2000 Oct;106(7):887-95. doi: 10.1172/JCI10483.


To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6(+/+)) or IL-6 gene knockout (il6(-/-)) mice that were fed either control or ethanol liquid diets for 4 months. In the il6(+/+) mice, ethanol ingestion decreased bone mineral density, as determined by dual-energy densitometry; decreased cancellous bone volume and trabecular width and increased trabecular spacing and osteoclast surface, as determined by histomorphometry of the femur; increased urinary deoxypyridinolines, as determined by ELISA; and increased CFU-GM formation and osteoclastogenesis as determined ex vivo in bone marrow cell cultures. In contrast, ethanol ingestion did not alter any of these parameters in the il6(-/-) mice. Ethanol increased receptor activator of NF-kappaB ligand (RANKL) mRNA expression in the bone marrow of il6(+/+) but not il6(-/-) mice. Additionally, ethanol decreased several osteoblastic parameters including osteoblast perimeter and osteoblast culture calcium retention in both il6(+/+) and il6(-/-) mice. These findings demonstrate that ethanol induces bone loss through IL-6. Furthermore, they suggest that IL-6 achieves this effect by inducing RANKL and promoting CFU-GM formation and osteoclastogenesis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Alcoholism / complications*
  • Animals
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / etiology*
  • Cell Differentiation
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Osteoclasts / cytology*


  • Interleukin-6