Excessive bone resorption by osteoclasts can lead to disability as well in inflammation induced bone erosion such as Rheumatoïd Arthritis as in non-inflammation dependent bone diseases such as postmenopausal osteoporosis. We have shown that sialoadhesin has a role in osteoclastogenesis as its deficiency or blocking inhibits osteoclastogenesis ex vivo in mouse and human and in vivo in mice, either non-diseased or during arthritis. Based on these results, we are currently preparing a patent application. In this project we want to establish the proof of concept of blocking sialoadhesin in a non-inflammation dependent bone disease to be able to validate our target in a broad scope of relevant bone disorders depending on osteoclast function. As a model for postmenopausal osteoporosis we will perform ovariectomy on wildtype and sialoadhesin deficient mice to provide proof of concept of the role of sialoadhesin in osteoclastogenesis and in particular in osteoporosis. A monoclonal anti-sialoadhesin antibody will be optimised in order to be minimally immunogenic and produced and purified in quantities for validation in this mouse model. This will serve as a prototype for future sialoadhesin targeted therapeutic molecules for proof of concept studies in other disease models. Furthermore, elucidation of the precise mechanism of osteoclast inhibition by blocking sialoadhesin, will illustrate the possible novelty of mode of action, next to the novelty of the therapeutic target.