However, as rare variants in several genes, including LRP5, can be found in the general population that are predicted to be (likely) pathogenic or of undetermined significance it is not always easy to link these variants to the patient’s osteoporosis, especially when segregation analysis in the family is not possible due to lack of large pedigrees or when family members have low BMD due to other (non-genetic) causes [47]. Here, LRP5 is linked to osteoporosis.