Evidence for a major gene for bone mineral density in idiopathic osteoporotic families

Although there have been a number of studies indicating a heritable component for osteoporosis in middle to late adulthood, the etiology of osteoporosis in young people is uncertain. The present study aims to evaluate the extent to which genetic factors influence familial resemblance for bone mineral density (BMD) in families ascertained on the basis of young osteoporotic probands. The sample comprises eight families (74 total individuals) that were identified through a proband under the age of 35 years with a history of two or more fractures and a spinal bone density of at least 2.5 SDs below the mean for age and sex (Z score). Secondary causes of osteoporosis were excluded in the probands. In total, 27% (18/66) of the probands' relatives had osteoporosis and an additional 30% (20/66) had osteopenia. Classical segregation analysis was performed to evaluate the extent to which a genetic etiology could account for familial resemblance in these families. The results indicate a major gene of codominant inheritance for spinal BMD. Model-fitting comparisons revealed no support for environmental effects or for polygenic inheritance.