alexa Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures.
Toxicology

Toxicology

Journal of Drug Metabolism & Toxicology

Author(s): Giuliani N, Girasole G, Vescovi PP, Passeri G, Pedrazzoni M

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Abstract Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a consequence of both systemic and direct cellular effects. To clarify some of the pathways by which alcohol exerts its actions directly on bone cells, we investigated the formation of early osteoblast progenitors (colony-forming units for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F formation (maximal reduction +/- SEM: 50 +/- 2\%; p < 0.01) at concentrations ranging from 0.04\% to 0.6\% that are similar to those reached in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004\% and 0.02\%, and completely abolished it at the dose of 0.06\%. Similarly, ethanol (at concentrations > or =0.02\%) and acetaldehyde (from 0.004\% to 0.06\%) significantly decreased the number of CFU-F in human bone marrow cultures; the mean reduction observed with ethanol was 63 +/- 12\% (p < 0.05), whereas acetaldehyde completely prevented CFU-F formation at the concentration of 0.06\%. These in vitro observations were confirmed by the in vivo findings that the CFU-F formation in bone marrow cultures from nine young, chronic, noncirrhotic alcoholics was significantly reduced (70 +/- 15\%), compared with seven age-matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol reduced proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of the bone marrow, and this effect may contribute to the decreased bone formation observed in alcoholics.
This article was published in Alcohol Clin Exp Res and referenced in Journal of Drug Metabolism & Toxicology

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