Metabolic mediators play an important role in regulating inflammation(1). Rheumatoid arthritis and spondyloarthritis are common inflammatory diseases of the joint, aggravated in context of obesity(2). These patients experience systemic bone loss(3,4), which is not sufficiently controlled by disease-modifying therapeutics, despite adequate control of inflammation(5,6). Here we report an unexpected role for GDF15 (Growth Differentiation Factor 15), a central mediator of food intake(7–10), in inflammation-associated bone loss. Serum GDF15 levels were found to be elevated in arthritis patients and inversely correlated with bone density. However, GDF15 itself does not appear to promote arthritis. Rather, GDF15 mediates trabecular bone loss through its receptor GFRAL, which is expressed exclusively in the hindbrain(7–10). GDF15-GFRAL binding results in β-adrenergic activation of bone Marrow Adipogenic Lineage Precursors (MALPs), mesenchymal cells which are known to stimulate osteoclasts and trigger bone loss(11–14). These data demonstrate how a metabolic mediator controls bone loss through a brain-bone axis in inflammatory diseases. These findings may lead to more specific therapeutic interventions to protect bone through targeting GDF15 or MALPs.