Several mechanisms can cause hypercalcemia in malignancies, in 80% of cases parathyroid hormone-related protein (PTHrP) acts on osteoblasts causing increased expression of receptor activator of nuclear factor kappa-B ligand (RANKL)  ultimately leading to activation of osteoclasts, bone resorption and increased reabsorption of calcium from kidneys causing hypercalcemia [19]. This evidence concerns the gene TNFSF11 and hypercalcemia disease.