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

Alcohol abuse is commonly associated with reduced bone mass and osteoporosi s 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 (colon y-forming units for fibroblasts; CFU-F) in long-term murine end 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 reac hed in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004% and 0.02%, and completely abolished rt at the dos e of 0.06%. Similarly, ethanol (at concentrations greater than or equal to 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 pre vented CFU-F formation at the concentration of 0.06%. These in vitro observ ations were confirmed by the in vivo findings that the CFU-F formation in b one marrow cultures from nine young, chronic, noncirrhotic alcoholics was s ignificantly reduced (70 +/- 15%), compared with seven age-matched normal s ubjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol r educed proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of th e bone marrow, and this effect may contribute to the decreased bone formati on observed in alcoholics.