A FKBP5 mutation is associated with Paget’s disease of bone and enhances osteoclastogenesis

A rare case of familial Pagets disease of bone in Han Chinese reveals a mutation in a gene not previously associated with the condition. Paget’s disease of bone disrupts the normal cycle of bone degradation and repair, causing bone pain, deformity and fractures. It is rarely diagnosed in Asian populations, but is the second most prevalent chronic bone disorder among Europeans. Yueran Zhao at Shandong University, China, and colleagues show that a mutation harbored by three members of one family disrupted signalling pathways involved in the breakdown of bone tissue. Experiments in cell lines and transgenic mice demonstrated that the identified mutation stimulated the differentiation of precursor cells into osteoclasts, the multinucleated cells responsible for bone degradation, thus shedding further light on the mechanisms underlying the disease.