Human patients carry RANK mutations and mice lacking RANKL or RANK exhibit a defect in B cell development, resulting in a significant reduction in B cell numbers (47, 49); however, these effects might be indirect because in the mouse, tissue-specific deletion of Rank in B cells showed no difference in function nor development of B cells, and blocking RANK/RANKL with Denosumab does not apparently affect B cell physiology in osteoporosis patients (58, 59). Here, TNFRSF11A is linked to osteoporosis.