Molecular genetics of calcium sensing in bone cells

The molecular mechanisms regulating bone remodelling are only partially understood. One of the controversial issues discussed during the past few years is the role that calcium signalling plays in this process and, in particular, in the functioning of the osteoclast. Calcium is involved in the recruitment and activation of osteoclasts and their subsequent detachment from bone. Parathyroid hormone and vitamin D are part of a systemic mechanism regulating calcium availability, storage and disposal. But there are conflicting results suggesting the presence of a local calcium-sensing mechanism in osteoclasts, in osteoblasts or in both. If this system could be characterized, it would be of therapeutic relevance for diseases such as postmenopausal osteoporosis and rheumatoid arthritis. Genetic data, animal models and cell-based assays have not yet been used to their full extent in this area. Here we review the available data and outline possible future strategies.