Interestingly, administration of osteoprotegerin (OPG), a soluble decoy receptor of RANKL, sharply reduced osteoclastogenesis, bone destruction, cancer-induced pain behaviors, and spinal astrocyte activation.37 This study also nicely demonstrates the difficulty in parsing out the relative contributions of tumor cells, osteoclasts, and activated spinal glial cells to nociceptor activation and pain in bone cancer because each of these components are intricately linked and it is difficult to alter one without reciprocally influencing the others. The gene discussed is TNFRSF11B; the disease is cancer.