Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?
OBJECTIVE
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.
Heikkinen
A M
AM
Department of Obstetrics and Gynecology, Kuopio University Hospital, Finland. anna-mari.heikkinen@pp.inet.fi
Kröger
H
H
Niskanen
L
L
Komulainen
M H
MH
Ryynänen
M
M
Parviainen
M T
MT
Tuppurainen
M T
MT
Honkanen
R
R
Saarikoski
S
S
D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D017698:Postmenopause
D001057:Apolipoproteins E; D015415:Biomarkers