title: Osteoprotegerin abrogates chronic alcohol ingestion-induced bone loss in mice.
abstract: To investigate the role of osteoprotegerin (OPG) on alcohol (ethanol)-mediated osteoporosis, we measured a variety of bone remodeling parameters in mice that were either on a control diet, an ethanol (5%) diet, or an ethanol (5%) diet plus OPG administration. OPG diminished the ethanol-induced (1) decrease in bone mineral density (BMD) as determined by dual-energy densitometry, (2) decrease in cancellous bone volume and trabecular width and the increase of osteoclast surface as determined by histomorphometry of the femur, (3) increase in urinary deoxypyridinolines (Dpd's) as determined by ELISA, and (4) increase in colony-forming unit-granulocyte macrophage (CFU-GM) formation and osteoclastogenesis as determined by ex vivo bone marrow cell cultures. Additionally, OPG diminished the ethanol-induced decrease of several osteoblastic parameters including osteoblast formation and osteoblast culture calcium retention. These findings were supported by histomorphometric indices in the distal femur. Taken together, these data show that OPG diminishes ethanol-induced bone loss. Furthermore, they suggest that OPG achieves this through its ability to abrogate ethanol-induced promotion of osteoclastogenesis and promote osteoblast proliferation.
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinlu
authors.initials: J
authors.lastname: Dai
authors.forename: Din-Lii
authors.initials: DL
authors.lastname: Lin
authors.forename: Paula
authors.initials: P
authors.lastname: Habib
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Jill
authors.initials: J
authors.lastname: Murtha
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Qi
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D006023:Glycoproteins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; D000431:Ethanol; D002118:Calcium