Objectives: Bone mineral density (BMD) and development of osteoporosis are partly determined by genetic factors. The associations between one of suggested candidate, apolipoprotein E (apo E) genotype to bone mineral density (BMD) and bone biochemical markers was studied in 464 subjects recruited from a population-based group of early postmenopausal women (n = 13100). Additionally, the influence of apo E genotype on BMD changes during a 5-year follow-up with or without hormone replacement therapy (HRT) was investigated.
Methods: Participants were randomized into two treatment groups: HRT group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU/day + calcium lactate, 500 mg/day (n = 232), and the non-HRT group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 100-300 IU/day (n = 232). BMD was measured from the lumbar spine and proximal femur at baseline and after 5 years of treatment (n = 352). In a subgroup (n = 59), the serum concentrations of bone biochemical markers (intact osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I collagen carboxy-terminal telopeptide (ICTP)) were measured at baseline and after 1 year of follow-up.
Results: At baseline, the BMDs were similar between the five apo E genotype groups (2/3, 2/4, 3/3, 3/4, 4/4). No significant differences in lumbar or femoral neck BMDs of women with the apo E4 allele were found compared with those without it. There was a statistically significant difference in 5-year BMD changes between the HRT and non-HRT groups. After 5 years, the BMD of the femoral neck had remained constant and the mean lumbar spine BMD had increased by 1.5% in the HRT group, whereas both BMDs had decreased by 4-5% in the non-HRT group. However, the apo E genotype did not modify the changes in BMD in either group. Additionally, the baseline concentrations of bone metabolic markers and their 1-year changes showed no genotype-related associations.
Conclusions: The results of our population-based study indicate that apo E genotype does not modify lumbar or femoral neck BMDs or serum bone biochemical markers or their response to HRT in early postmenopausal Caucasian women.