cell survival by inhibiting TRAIL-induced apoptosis of tumour cells. Bone metastasis Bone is a common site of metastasis in cancers such as breast, prostate and lung cancer. In osteolytic bone metastases, tumour cells migrate to the bone and release cytokines such as parathyroid hormone-related protein (PTHrP), IL-8 and PGE2. These cytokines act on osteoblasts to increase RANKL and decrease OPG expression resulting in excess bone resorption. During resorption osteoclasts release nutrients such as growth factors and calcium from the mineralised bone matrix which cultivates a supportive environment for the proliferation and survival of tumour cells. Most bone metastases result in osteolytic lesions, however prostate cancer causes osteoblastic lesions characterised by excess bone formation and high bone density. Prostate cancer releases cytokines such as insulin-like growth factor (IGF), endothelin-1, bone morphogenetic proteins (BMPs), sclerostin and Wnt proteins that act on local bone to increase osteoblast proliferation and activity. Wnt proteins also act on osteoblasts to upregulate OPG expression through β-catenin signalling and suppress osteoclastic bone resorption. Multiple myeloma Multiple myeloma is a type of cancer involving malignant plasma cells, called myeloma cells, within the bone marrow. Multiple myeloma is associated with osteolytic bone lesions as the usually high levels of OPG in the bone marrow are diminished resulting in increased osteoclastic absorption. The reduced OPG in multiple myeloma is caused by suppression of both constitutive OPG transcription and the OPG inducing cytokines TGF-β and Wnt. In addition, the efficacy of OPG in bone marrow is impeded with multiple myeloma by excessive binding to syndecan-1. OPG binds to syndecan-1 on the surface of normal and multiple myeloma plasma cells to be internalised and degraded. However the overabundance of proliferating myeloma cells results in the excessive binding and inhibition of OPG by syndecan-1. Simultaneously, multiple myeloma is associated with unusually high levels of osteoclastogenesis-inducing factors. The decreased OPG transcription and increased OPG protein degradation combined with increased osteoclastogenesis result in the osteolytic lesions that are characteristic of multiple myeloma. Otosclerosis Otosclerosis is a disorder of the middle ear, characterized by abnormal bone growth at the foot plate of the stapes which affect its mobility, resulting in progressive hearing loss. OPG gene polymorphisms c.9C>G and c.30+15C> have shown genetic association with OTSC in Indian and Tunisian populations. Some of the reports have shown significantly reduced or missing OPG expression in otosclerotic tissues which might be a causal factor for abnormal bone remodeling during disease