Genetics of male osteoporosis

In the past years, several epidemiological and clinical observations have underlined the importance of genetics in the pathogenesis of both female and male osteoporosis. It has been estimated that from 50 to 80% of the inter-individual variability in bone mass is genetically determined. In rare instances, osteoporosis in men could be inherited in a simple Mendelian pattern. Examples of this include familial osteoporotic syndromes due to mutations in the aromatase and ER alpha genes. Families have also been described in which high bone mass is inherited as an autosomal dominant trait, consistent with the effect of a single gene located on chromosome 11. However, except for these rare conditions, osteoporosis has to be considered a multifactorial disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. The genetic effect on bone may also be gender- and site-specific, with different genes regulating bone density at different skeletal sites in males and females. To date, most of the work on the genetics of osteoporosis has focused on women. In some studies, polymorphisms at the IGF-I, VDR, COLI-alpha1, ER alpha, and aromatase gene have been recently shown to predict BMD variation and osteoporotic risk in males. These observations remain to be confirmed by other independent studies. Other candidate genes, are still awaiting mapping and identification.