In addition to liver disease, alcoholics are at risk of other ailments, including fragile bones. Osteopenia in these individuals might be explained by a deficit in osteoblast-dependent bone deposition, an excess of osteoclast-dependent bone resorption, or both. Dai et al show here that these effects each contribute to bone fragility in mice exposed over 4 months to ethanol in their drinking water. They also show that IL-6, a known inducer of osteoclast formation, is required for ethanol's effects on bone resorption.

Since ethanol can induce IL-6 expression in cultured marrow stromal cells, Dai and coworkers compared the differentiation of marrow cells from wild type and IL6-/- knockout mice. IL-6-deficient cultures failed to accumulate osteoclast precursors in response to ethanol or to upregulate expression of RANK ligand, which promotes the formation of mature osteoclasts. By several measures, bone mass was better maintained in alcohol-fed IL6-/- mice than in wild type animals, suggesting that the loss of osteoclast induction improves the mechanical strength of the bone. The residual effects of alcohol on bone mass in IL6-deficient animals might be explained by loss of bone deposition.

Alcohol feeding did not interfere with osteoblast proliferation, but it did cause a significant block in osteoblast function in both genotypes, as seen in calcium retention in cultured osteoblasts. Hence, reduced bone deposition is largely IL-6-independent but would be expected to act in concert with an IL-6 dependent increase in bone turnover to weaken the bones, increasing the high incidence of fractures among alcoholics.