The genetics of osteoporosis: 'complexities and difficulties'

Osteoporosis is characterized by a decrease in bone mass as well as a deter ioration of the bone architecture resulting in an increased risk of fractur e. Although the disease is multifactorial, twin studies have shown that gen etic 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 t he vitamin D and estrogen receptor genes, as well as the collagen type I al pha 1 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 eac h candidate gene is expected to be modest, discrepancies between allelic as sociation studies may have arisen because different populations carry diffe rent genetic backgrounds and exposure to environmental factors. Also, we re alize the importance of gene-gene as well as gene-environment interactions as significant determinants of bone density and risk of osteoporosis. The u se of new tools such as small nucleotide polymorphism maps now allows the p ossibility to perform allelic association studies in the context of whole-g enome search. However, specific study design strategies in large epidemiolo gical studies as well as the best statistical approach will need to be esta blished. We may expect the development of population-specific at-risk profi les for osteoporosis that would include genetic and environmental factors, as well as their interactions. This should eventually lead to better preven tion strategies and more adapted therapies against osteoporosis.