(1) There is no relationship between VDR and ERalpha genes polymorphism and the stage of osteoporosis related to the spinal BMD value before treatment. (2) The XX, PP or Bb markers or only X, P, B alleles are connected with a significant decrease of treatment efficacy. (3) Estradiol serum concentration before and during HRT is not dependent on the polymorphism of VDR and ERalpha genes.