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Selective Fat Cell Elimination in Mice Leads to a Profound Increase in Bone Mass

By studying how fat cells in the bone marrow of mice affect bone growth, researchers studying mice have discovered potential therapeutic targets that may profoundly increase bone mass to prevent or restore bone loss. Osteoporosis, a bone disease that occurs when the body loses bone mass, is endemic in Western and Asian societies and predisposes older adults to weak bones, fractures, and premature mortality. Recent evidence that fat cell depletion can trigger bone growth hints at the potential for new osteoporosis therapeutic strategies.

In the current study, researchers generated male and female mice in which administering a chemical could eliminate fat cells, including in bone marrow, which contains fat cells, and in other body fat tissue. They found that within 10 days of being given the chemical, bone growth increased 10-fold in mice without fat cells compared to mice with fat cells intact. New bone mass was markedly increased in older mice but to a lesser extent in young mice, and the new bone had enhanced strength and function compared to bones of mice with normal fat distribution. Moreover, researchers found that while removing the ovaries of normal female mice that results in osteoporosis, those in the group that received the chemical and lacked fat cells were protected from bone loss. The researchers next investigated whether the bone growth was caused by depletion of fat cells in bone marrow or in other body fat tissues, in part by seeing whether the effects changed if they restored some fat tissue. When fat tissue from normal mice was transplanted under the skin of mice lacking fat, there was no effect on bone growth. This and other experiments suggested that bone formation is specifically inhibited by fat cells in the bone marrow, rather than by fat in other tissues. Further analysis indicated that marrow fat cells might be tamping down a signaling pathway previously associated with bone growth, providing potential therapeutic targets that may be considered to treat osteoporosis in humans. Because chronic activation of this pathway can lead to excessive growth of other several cell types, the use of this strategy to treating bone disease may result in other yet unknown effects may present roadblocks.

Moreover, further research is needed to determine if bone growth in humans is similarly affected by marrow fat cells, and, if so, to identify strategies for stimulating bone growth that may one day improve treatment or prevention of osteoporosis.

Zou W, Rohatgi N, Brestoff JR,…Teitelbaum SL. Ablation of fat cells in adult mice induces massive bone gain. Cell Metab. 32: 801-813, 2020.