Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: Effect of hormone replacement therapy

Genetic factors regulate bone mineral density (BMD) and possibly the develo pment of osteoporosis. An association between estrogen receptor (ER) polymo rphism, BMD, and postmenopausal hormone replacement therapy (HRT) has not b een established. Therefore, we studied the influence of the ER genotype on BMD before and after a 5-year HRT in a placebo-controlled, population-based , randomized group of 322 early postmenopausal women, The participants were randomized into two treatment groups: the HRT group (n = 145) received a s equential combination of 2 mg estradiol valerate and 1 mg CPA with or witho ut vitamin D-3, 100-300 ns + 500 mg calcium lactate/day (equal to 93 mg Ca2 +), and the non-HRT group (n = 177) received calcium lactate, 500 mg alone or in combination with vitamin D3, 10-300 IU/day, PvuII restriction fragmen t length polymorphism (RFLP) of the ER alpha was determined using polymeras e chain reaction (PCR). BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual-energy X-ray absorptiometry (DXA), At the basel ine, there were no significant differences in the lumbar or femoral neck BM Ds between the three ER PvuII genotype groups (PP, Pp, pp), After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4- 5% in the non-HRT group. The ER genotype did not modulate the femoral neck BMD change during the follow-up. In contrast, in the non-HRT-group the lumb ar spine BMD decreased more in subjects,vith the ER genotypes PP (6.4%) and Pp (5.2%) than in subjects with the pp genotype (2.9%) (p = 0,002), In the HRT group, the relative changes of the lumbar spine BMD were similar in al l three ER genotype groups, Thus without HRT, the pp genotype was associate d with a smaller decrease in the lumbar spine BMD than the Pp and PP genoty pes, Long-term HRT seemed to eliminate the ER genotype-related differences in the BMD, We conclude that subjects with the ER PvuII genotypes PP and Pp may have a greater risk of relatively fast bone loss after menopause than those with the pp genotype and that they may preferentially derive benefit from HRT.