Detailed Instructions: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
See one example below:
Problem: In 1582 the united provinces invited francis, duke of anjou to lead them; but after a failed attempt to take antwerp in 1583, the duke left the netherlands again. after the assassination of william of orange (10 july 1584), both henry iii of france and elizabeth i of england declined the offer of sovereignty. however, the latter agreed to turn the united provinces into a protectorate of england (treaty of nonsuch, 1585), and sent the earl of leicester as governor-general. this was unsuccessful and in 1588 the provinces became a confederacy. the union of utrecht is regarded as the foundation of the republic of the seven united provinces, which was not recognized by the spanish empire until the peace of westphalia in 1648.
Solution: In what year did francis, duke of anjou leave the netherlands?
Explanation: The generated question is perfect. Because the question is based on second sentence of the input passage and its answer is 1583.

Problem: Bone, as well as the lung and liver, is among the sites of predilection for cancer metastasis. The bone stores large amounts of growth factors such as insulin-like growth factors and transforming growth factor-b, and provides fertile soil for metastatic cancer cells by continuously releasing these bone-stored growth factors, which are a consequence of osteoclastic bone resorption. Metastatic cancer cells in turn produce osteoclast-stimulating cytokines such as parathyroid hormone-related protein( PTH-rP), prostaglandin E2.(PGE2), and various interleukins(ILs). These cancer-produced osteoclast-stimulating cytokines bind to their cognitive receptors and promote the expression of ligands for the receptor activators of nuclear factor kB (RANKL)in osteoblasts. RANKL then binds to its receptor RANK, expressed in pre-osteoclasts, stimulates mature osteoclast formation, and subsequently, osteoclastic bone resorption. This vicious cycle between metastatic cancer cells and osteoclasts is critical to the development and progression of bone metastases. In addition, it is likely that metastatic cancer cells are influenced by bone environments(or niche)and acquire additional capacities such as an epithelial-mesenchymal transition(EMT), allowing them to be resistant to chemotherapy or apoptosis, to survive in a dormant state, or to aggressively spread to distant organs including lung and liver. Thus, the bone can serve as transit port. Disrupting this cycle by inhibiting osteoclastic bone resorption, antagonizing bone-derived growth factors, and neutralizing RANKL or PTH-rP, should be a promising therapeutic intervention for bone metastases. Bisphosphonates(BP)are specific inhibitors of osteoclasts, and have been shown to significantly reduce skeletal-related events(SRE)associated with bone metastasis. Denosumab is a neutralizing monoclonal antibody to RANKL and has recently been found to inhibit SRE more effectively than BP. Further understanding of the crosstalk communication between metastatic cancer cells and bone at the molecular level should lead us to design novel, more effective and specific treatments for cancer patients with bone metastases.
Solution:
To the ligand of which receptors does Denosumab (Prolia) bind?