OA is a polygenic disease, and researchers conducting OA genomic studies have focused on typically diagnosed cases of age-related disease, which begins in the fifth decade of life.[12] In a phenotype-wide association study using the UK Biological Database, heterozygotes for the Z allele of SERPINA1 (rs28929474) were associated with multiple musculoskeletal phenotypes, including reduced risk of OA but increased risk of osteoporosis and reduced bone mineral mass.[13] AAT inhibited osteoclast formation and bone resorption induced by RANKL. Here, SERPINA1 is linked to osteoporosis.