title: Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study.
abstract: OBJECTIVE
  To determine the relationships among bone mineral density changes, bone marker changes, and plasma estrogens in postmenopausal women receiving estrogen replacement therapy.
  
  
  METHODS
  A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens (0.3 mg, 0.625 mg, or 1.25 mg) or placebo daily for up to 24 months. Bone mineral density and bone marker measurements were determined at 6-month intervals; plasma estrogens were measured in a subset after 12, 18, and 24 months.
  
  
  RESULTS
  Esterified estrogens produced significant increases in bone mineral density (lumbar spine, hip) compared with baseline and placebo at 6, 12, 18, and 24 months. Bone markers decreased from baseline with all esterified estrogen doses relative to placebo. Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months (correlation coefficient range = -0.122 to -0.439). The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin. Mean plasma estrogen levels increased with esterified estrogen dose, and bone mineral density changes correlated positively with plasma estrogen levels. Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL.
  
  
  CONCLUSIONS
  Esterified estrogens, at doses from 0.3 mg to 1.25 mg/day, unopposed by progestin, increase bone mineral density of the spine and hip in postmenopausal women. These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12, 18, or 24 months. Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy.
authors: Emory University, Atlanta, Georgia, USA.
authors: N B
authors: NB
authors: Watts
authors: J C
authors: JC
authors: Nolan
authors: J J
authors: JJ
authors: Brennan
authors: H M
authors: HM
authors: Yang
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood*; D045166:Estradiol Congeners; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D045166:Estradiol Congeners; D004967:Estrogens; D015675:Osteocalcin; C084328:Estratab; D004958:Estradiol; C015484:pyridinoline; C036020:deoxypyridinoline; D002118:Calcium