During the early part of this past decade, several reports linked changes in bone mass to alterations in LRP5. The first report found that patients with osteoporosis pseudoglioma syndrome (OPPG), an autosomal recessive disorder in which afflicted individuals develop severe, early-onset osteoporosis [47], are homozygous for inactivating mutations in LRP5  [48]. Here, LRP5 is linked to osteoporosis-pseudoglioma syndrome.