title: In vitro evaluation of dose-effects of ethanol on human osteoblastic cells.
abstract: Chronic alcoholism represents a high risk for fractures and osteopenia. Previous histomorphometric studies reported a decreased bone formation, but it has never been established whether ethanol has a direct toxic effect on osteoblasts. This present in vitro study was performed on human osteoblast cells derived from bone explants after collagenase digestion. The direct effect of ethanol was determined after 4 days of exposure to various doses, ranging from 0.01 to 5 g/l on the alkaline phosphatase (AP) activity, osteocalcin secretion and [3H]thymidine incorporation. The influence of the duration of exposure to 0.8 g/l ethanol was also determined. A significant and dose-dependent decrease in the cell proliferation was observed. AP activity was significantly decreased by high doses of ethanol (2-5 g/l). A biphasic effect of ethanol was noted on osteocalcin secretion according to the dose: it decreased at doses lower than 0.8 g/l and increased at the highest concentrations. At the dose of 0.8 g/l, whatever the duration of exposure, the decrease of the proliferation was of the same magnitude and no significant change in AP activity was observed. Significant ethanol-induced effects on osteocalcin secretion were observed only after 4 and 8 days of exposure. These data demonstrate that ethanol may have a direct toxic effect on osteoblast activity and proliferation. This could be one of the mechanisms of alcohol-induced osteopenia which has a multifactorial pathophysiology.
authors.affiliation: INSERM Unité 234, Faculté A. Carrel, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Chavassieux
authors.forename: C M
authors.initials: CM
authors.lastname: Serre
authors.forename: P
authors.initials: P
authors.lastname: Vergnaud
authors.forename: P D
authors.initials: PD
authors.lastname: Delmas
authors.forename: P J
authors.initials: PJ
authors.lastname: Meunier
mesh_terms: D000437:Alcoholism; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000139:chemically induced; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism
chemical_list: D015675:Osteocalcin; D000431:Ethanol; D000469:Alkaline Phosphatase; D002117:Calcitriol