Objectives: Bone mineral density (BMD) and development of osteoporosis are
partly determined by genetic factors. The associations between one of sugge
sted candidate, apolipoprotein E (apo E) genotype to bone mineral density (
BMD) and bone biochemical markers was studied in 464 subjects recruited fro
m a population-based group of early postmenopausal women (II = 13 100). Add
itionally, the influence of apo E genotype on BMD changes during a 5-year f
ollow-up with or without hormone replacement therapy (HRT) was investigated
. Methods: Participants were randomized into two treatment groups: HRT grou
p: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone a
cetate with or without vitamin D-3, 100-300 IU/day + calcium lactate, 500 m
g/day (n = 232), and the non-HRT group: Calcium lactate, 500 mg/day alone o
r in combination with vitamin D-3, 100-300 IU/day (n = 232). BMD was measur
ed from the lumbar spine and proximal femur at baseline and after 5 years o
f treatment (n = 352). In a subgroup (n = 59), the serum concentrations of
bone biochemical markers (intact osteocalcin (OC), bone-specific alkaline p
hosphatase (BAP) and type I collagen carboxy-terminal telopeptide (ICTP)) w
ere measured at baseline and after 1 year of follow-up. Results: At baselin
e, 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 o
f women with the apo E4 allele were found compared with those without it. T
here was a statistically significant difference in 5-year BMD changes betwe
en the HRT and non-HRT groups. After 5 years, the BMD of the femoral neck h
ad 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 grou
p. 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. Conclusio
ns: The results of our population-based study indicate that apo E genotype
does not modify lumbar or femoral neck BMDs or serum bone biochemical marke
rs or their response to HRT in early postmenopausal Caucasian women. (C) 20
00 Elsevier Science Ireland Ltd. All rights reserved.