Osteoporosis is one of our major public health problems. Bone fractures caused by osteoporosis lead to great suffering and significant costs for the patients affected.The inhabitants of Sweden and Norway have the highest risk of bone fractures in the world. The reason for this is unknown and it is therefore of great strategic importance to conduct osteoporosis research in Sweden. The overall objectives of the application are to develop more effective and safer treatment methods for patients with osteoporosis and to increase knowledge of the causes of osteoporosis. The studies include both experimental animal studies and clinical patient studies. I have recently identified a number of genetic risk markers and potential drug targets for bone fractures. We will evaluate whether the identified genetic regions that have been shown to increase the risk of osteoporosis are indeed important for bone fracture risk and if so, we will investigate in detail how they affect fracture risk. My human genetic studies and subsequent studies in transgenic mice have recently shown that the endogenous protein WNT16 reduces the risk of bone fracture by increasing the thickness of compact bone. We are now using advanced cell culture systems and transgenic mice to investigate in detail how WNT16 protects against bone fractures. Our working hypothesis is that WNT16 is released from the bone-forming osteoblasts and inhibits the bone-degrading osteoclasts.