title: Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, Finland. anna-mari.heikkinen@pp.inet.fi
authors.forename: A M
authors.initials: AM
authors.lastname: Heikkinen
authors.forename: H
authors.initials: H
authors.lastname: Kröger
authors.forename: L
authors.initials: L
authors.lastname: Niskanen
authors.forename: M H
authors.initials: MH
authors.lastname: Komulainen
authors.forename: M
authors.initials: M
authors.lastname: Ryynänen
authors.forename: M T
authors.initials: MT
authors.lastname: Parviainen
authors.forename: M T
authors.initials: MT
authors.lastname: Tuppurainen
authors.forename: R
authors.initials: R
authors.lastname: Honkanen
authors.forename: S
authors.initials: S
authors.lastname: Saarikoski
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers