Osteoporosis is a common skeletal disease characterized by reduced bone mineral density (BMD) and increased risk of low trauma fractures [4]. In the United States, it has been estimated that the prevalence rate of osteoporosis in older adults was about 10.3%, while low bone mass prevalence rate was 43.9% [5]. In China, the prevalence rate of osteoporosis in older adults was estimated to be 15.7%, and it will increase rapidly with the increasing age of the total population [6]. Despite the significant impact on human health, there is still a lack of highly effective osteoporosis treatments that are free of negative side effects [7]. Hence, identification of additional therapeutic molecular targets for effective and efficient prevention and treatment of osteoporosis are needed. Heritability for BMD is estimated to be > 50% [8,9] and more than one hundred loci have been found to be associated with BMD or osteoporosis by previous studies [10–16]. However, although many associated genetic variants have been identified by GWAS, the causal variants truly with biological effects have remained largely unknown. Furthermore, only ~10% of the total
