Given the well-established role of osteoprotegerin as an osteoclast inhibitor [56], the outcome of systemic osteoprotegerin application does not bear any surprises, but the osteolysis promoting effects in [12], as well as the increased osteolysis in metastatic cancer patients with high levels of circulating osteoprotegerin [10], [11], appear to be contradictory. This evidence concerns the gene TNFRSF11B and metastatic malignant neoplasm.