Alcohol-induced adipogenesis in bone and marrow: a possible mechanism for osteonecrosis

The effect of alcohol on rabbit bone marrow and on the differentiation of mouse bone marrow stromal cells was investigated. Alcohol was administered intragastrically at a dose of 10 mL/kg/day for 1 to 6 months. Alcohol induced a significant increase in serum lipid peroxides, triglyceride, and cholesterol, and a reduction in superoxide dismutase activity. Fatty infiltration in the liver and adipogenesis in bone marrow were found histologically after alcohol administration. Fat cell hypertrophy and proliferation and diminished hematopoiesis in the subchondral area of the femoral head were observed. Triglycerides were deposited in osteocytes, which became pyknotic, and the percentage of empty osteocyte lacunae increased. None of these abnormal changes were detectable in the control group. In the in vitro study, the marrow stromal cells were treated with increasing (0.03, 0.09, and 0.15 mol/L) concentrations of ethanol for 4 to 21 days. Alcohol induced the differentiation of the cells into adipocytes. The number of adipocytes increased with longer durations of exposure to ethanol and with higher concentrations. Cells treated with ethanol also showed diminished alkaline phosphatase activity and expression of osteocalcin. These novel findings indicate that alcohol can directly induce adipogenesis, decrease osteogenesis in bone marrow stroma, and produce intracellular lipid deposits resulting in the death of osteocytes, which may be associated with the development of osteonecrosis, especially in patients with long-term and excessive use of alcohol.