INHIBITION OF OSTEOBLASTIC CELL-PROLIFERATION AND ORNITHINE DECARBOXYLASE ACTIVITY BY ETHANOL

Low bone mass and an increased prevalence of skeletal fractures are ev ident in the alcoholic population. Histomorphometric analysis of skele tal tissue from alcoholic patients reveals reduced osteoblast number a nd suppressed bone formation activity, with relative sparing of resorp tive indexes. The decreased number of osteoblasts observed in alcoholi c subjects results from either impaired proliferation or accelerated s enescence. Polyamines and ornithine decarboxylase (ODC), the rate-limi ting enzyme for polyamine synthesis, are essential for cell proliferat ion in a variety of cell types. To determine whether the consequences of ethanol on osteoblast number involve the modulation of polyamine bi osynthesis, we examined the effect of ethanol on parameters of cell gr owth and ODC activity in a rat osteoblast-like osteosarcoma cell line (UMR 106-01). Ethanol markedly impaired DNA synthesis and cell prolife ration in a dose-dependent fashion. Difluoromethylornithine, a specifi c inhibitor of ODC activity, induced a similar inhibition of UMR 106-0 1 cell proliferation, indicating the importance of the polyamine pathw ay in this osteoblastic cell line. Induction of ODC activity was impai red in ethanol-exposed cell cultures in a dose-dependent fashion that paralleled the antiproliferative effects. Finally, supplemental polyam ine administration substantially improved DNA synthesis in ethanol-exp osed UMR 106-01 cell cultures. These data confirm a direct inhibitory effect of ethanol on osteoblast proliferation that may in part explain the reduced bone mass observed in subjects who consume excessive amou nts of alcohol. These findings also suggest that altered polyamine met abolism may be an important mechanism responsible for the antiprolifer ative effects of ethanol on the osteoblast.