Genetics of male osteoporosis

In the past years, several epidemiological and clinical observations have u nderlined 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 inst ances, 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, consisten t with the effect of a single gene located on chromosome 11. However, excep t for these rare conditions, osteoporosis has to be considered a multifacto rial disease in which genetic determinants are modulated by hormonal, envir onmental, and nutritional factors. The genetic effect on bone may also be g ender- and site-specific, with different genes regulating bone density at d ifferent skeletal sites in males and females. To date, most of the work on the genetics of osteoporosis has focused on women. In some studies, polymor phisms at the IGF-I, VDR, COLI-alpha1, ER alpha, and aromatase gene have be en recently shown to predict BMD variation and osteoporotic risk in males. These observations remain to be confirmed by other independent studies. Oth er candidate genes, are still awaiting mapping and identification.