Vitamin D and bone formation parameters - genetic variation
H Namkung, J Patava, MD Slater, RS Mason
(collaborators: B Tuch, Dept of Endocrinology, Prince of Wales Hospital, Sydney; JA Eisman, C White, Garvan Institute of Medical Research, Sydney)

Genetic influences on bone density are known to be strong, but the identities of the genes responsible for this relationship are not clear. The Garvan group have described a relationship between particular vitamin D receptor allelles and bone density in adults, although this data has recently been modified. If genetic factors are involved, it is not clear whether they alter bone cell function, or gut or renal function. A bone cell formation model has been established in this laboratory. In this model, several parameters of bone forming activity including mineralization are modulated by 1,25(OH)₂D3. The availability of bone cells from different human donors, collected and maintained under similar conditions, provides a unique resource to examine possible genetic influences on bone cell function. To date 68 bone samples from different donors have been collected for these studies. Analyses showed that while there is consistency in different experiments in the response of bone cells from an individual donor to 1,25(OH)₂D3, the 1,25(OH)₂D3, response shows a very marked variation between cells from different donors. There is evidence that the influence of 1,25(OH)₂D3 on classic bone cell functional markers such as alkaline phosphatase activity and osteocalcin secretion may be influenced to some extent by vitamin D receptor genotype.