In the present report, WGS of a two-generation Maltese pedigree with early-onset familial osteoporosis and low BMD identified three rare and evolutionary conserved missense variants within SELP (c.2177T>C), TGF-β2 (c.1136C>T) and ADAMTS20 (c.4090A>T). This evidence concerns the gene SELP and osteoporosis.