Credit: Eye of Science / Science Source

Increased osteoclast activity is implicated in a number of bone loss conditions; thus, targeting bone resorption by osteoclasts could be a potential therapeutic avenue for these pathologies. A new study shows that the adenosine diphosphate (ADP) receptor P2RY12 regulates osteoclast function and can be therapeutically targeted in mouse models of bone loss (J. Clin. Invest. 122, 3579–3592).

ADP is known to increase osteoclast activity, so Xinming Su et al. decided to examine the role of P2RY12 in osteoclasts. Mice lacking P2RY12 showed decreased osteoclast activity in vivo and were partially protected from age-related bone loss. Bone marrow macrophages from P2ry12−/− mice could be differentiated ex vivo into mature osteoclasts, but these osteoclasts showed reduced resorption function and could not be stimulated by ADP to increase bone resorption.

The authors then tested the susceptibility of P2ry12−/− mice to various types of pathological bone loss and found that they were less susceptible than wild-type mice to arthritis-associated, tumor-associated and ovariectomy-induced bone loss. Su et al. also showed that clopidogrel, which inhibits P2RY12 and is a US Food and Drug Administration–approved antiplatelet drug, could partially protect wild-type mice from pathological bone loss.

Although there are currently no prospective data on the effects of clopidogrel on bone in patients being treated with this drug, clinical studies to evaluate this aspect may be useful to better assess the potential for therapeutically targeting P2RY12 in bone loss conditions.