ETHANOL INHIBITS HUMAN OSTEOBLASTIC CELL-PROLIFERATION

The habitual consumption of alcoholic beverages is clearly associated with low bone mass and an increased prevalence of skeletal fractures. Microscopic analysis of skeletal tissue from alcoholic patients reveal s reduced osteoblast number and suppressed bone formation activity wit h a relative sparing of resorptive indices. The decreased number of os teoblasts observed in alcoholic subjects results from either impaired proliferation or accelerated senescence. Polyamines and ornithine deca rboxylase (ODC), the rate-limiting enzyme for polyamine synthesis, are essential for cell proliferation in a variety of cell types. To deter mine if the adverse effect of ethanol on osteoblast number involves mo dulation of polyamine biosynthesis, we examined the effect of ethanol on parameters of cell growth and ODC activity in a human osteoblast-li ke osteosarcoma cell line (TE-85). Ethanol markedly impaired DNA synth esis and cell proliferation in a dose-dependent fashion, but alkaline phosphatase activity (a marker of differentiated osteoblast function) remained intact, and accelerated apoptosis was not evident. Thus, the reduced osteoblastic cell number was a result of a direct effect on pr oliferative processes rather than a nonspecific toxic effect of ethano l to accelerate cell death. Induction of ODC activity was impaired in ethanol-exposed cell cultures in a dose-dependent fashion that paralle led the antiproliferative effects. Finally, supplemental polyamine adm inistration substantially improved DNA synthesis in ethanol-exposed UM R 106-01 cell cultures. These data confirm a direct inhibitory effect of ethanol on osteoblast proliferation without overt cellular toxicity that may, in part, explain the reduced bone mass observed in those wh o consume excessive amounts of alcohol.