Vnitr Lek 2011, 57(1):78-84

Role of genetics in prediction of osteoporosis risk

I. Žofková

Endokrinologický ústav Praha, ředitel doc. MUDr. Vojtěch Hainer, CSc.

Osteoporosis is in 60-80% a hereditary disease with a characteristic multifactorial pathogenesis during which the effects of many "weak" genes interact with external factors. To date, most information relating to the correlations between genes and bone parameter variability (density, quality and metabolism) has been provided by association studies of candidate genes for osteoporosis. The best known genes related to bone density have been identified as the genes for the vitamin D, estrogen and calcitonin receptor, LRP5 and LRP6. The genes for IL-1α and osteoprotegerin are responsible for the parameters of bone remodeling. Recently discovered genes related to bone phenotype include identified genes for hypolactasia, tetrafolate reductase and ALDH7A1. Bone size and dimensions are probably partially controlled by the PLCL1 gene. Candidate genes for osteoporosis probably also determine the production of calciotropic hormones (PTH, sex steroids) and even some extra-osseous phenotypes (inflammation, immunity, susceptibility to malignancies). On the contrary, genes that determine extra-osseous parameters (e. g. lipoprotein levels) are associated with the bone phenotype (the gene for ApoE is related to bone density). Association studies, though, have serious limitations. Among others, these include the influence of linkage disequilibrium associated with the close proximity of the identified genes within DNA, which may be one of the causes of false positive results. In children, where building of the skeleton is influenced predominantly by external factors (nutrition, physical activity), the relationship between candidate genes and bone mass is less close than in adults. This overview deals with the physiology and sexual differentiation of pubertal bone. It discusses the importance of identifying candidate genes in the prevention and targeted treatment of osteoporosis (pharmacogenetics) as well as the application of the FRAX (WHO) program in the ten-year prediction of fractures in osteopenic patients.

Keywords: osteoporosis; genetics; candidate genes for osteoporosis; pubertal bone; prevention of osteoporosis; pharmacogenetics

Received: August 12, 2010; Accepted: October 21, 2010; Published: January 1, 2011  Show citation