The genetics of osteoporosis: ‘complexities and difficulties’

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. Although the disease is multifactorial, twin studies have shown that genetic factors account for up to 80% of the variance in bone mineral density, the best known predictor of the risk of osteoporosis. Some loci, such as the vitamin D and estrogen receptor genes, as well as the collagen type Iα1 locus, are promising genetic determinants of bone mass, and possibly other bone phenotypes, but this is controversial and the molecular basis of osteoporosis remains largely undefined. Considering that the effect of each candidate gene is expected to be modest, discrepancies between allelic association studies may have arisen because different populations carry different genetic backgrounds and exposure to environmental factors. Also, we realize the importance of gene–gene as well as gene–environment interactions as significant determinants of bone density and risk of osteoporosis. The use of new tools such as small nucleotide polymorphism maps now allows the possibility to perform allelic association studies in the context of whole‐genome