title: The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone.
abstract: OBJECTIVE
  Oestrogen replacement reduces the increased rate of bone remodelling after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast-mediated bone resorption. In vitro studies have shown that oestrogen stimulates OPG production. However, the role of OPG in physiological bone remodelling and its regulation by oestrogen in vivo remain controversial. In this study, we analysed the association between changes in serum OPG levels and bone turnover status before and after hormone therapy (HT) in healthy postmenopausal women.
  
  
  METHODS
  Ninety-nine healthy postmenopausal women of Korean ethnicity, aged 42-64 years (52.3 +/- 4.9 years, mean +/- SD) were enrolled in our study. Serum OPG levels were assessed by a highly sensitive sandwich-type enzyme immunoassay. Serum concentrations of osteocalcin (OC) and carboxyterminal telopeptides (CTx) were determined by electrochemiluminescence immunoassays. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry (DEXA).
  
  
  RESULTS
  Baseline levels of OPG correlated neither a the bone formation marker, serum OC, nor with a bone resorption marker, serum CTx. No significant association of baseline OPG was found with baseline BMD measured at the lumbar spine and femoral neck. Serum OPG levels measured after 3 months and 1 year of HT decreased significantly compared to baseline (P < 0.001 in both). The changes in circulating OPG at 3 months of HT correlated with the changes in both serum OC (r = 0.226, P = 0.029) and serum CTx (r = 0.214, P = 0.038) at 3 months after HT. However, there was no significant association between the changes in circulating OPG after 3 months of HT and BMD values of the lumbar spine or femoral neck after 1 year of HT.
  
  
  CONCLUSIONS
  Our results suggest that baseline OPG levels do not reflect bone turnover status and that serial measurements of serum OPG after HT are not a useful predictor of the long-term effects of oestrogen on bone density. The decrease in serum concentrations of OPG after HT may occur to compensate for the action of oestrogen in suppressing bone resorption.
authors.affiliation: Department of Medicine, Samsung Cheil Hospital and Women's Healthcare Centre, Sungkyunkwan University School of Medicine, Choong Gu Mukjung Dong, Seoul, Korea. kiok.han@samsung.com
authors.forename: Ki Ok
authors.initials: KO
authors.lastname: Han
authors.forename: Jong Tae
authors.initials: JT
authors.lastname: Choi
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Choi
authors.forename: In Gul
authors.initials: IG
authors.lastname: Moon
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Yim
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Park
authors.forename: Hyun Koo
authors.initials: HK
authors.lastname: Yoon
authors.forename: In Kwon
authors.initials: IK
authors.lastname: Han
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000375:Aging / Q000097:blood; D000704:Analysis of Variance; D000886:Anthropometry; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D005272:Femur Neck / Q000502:physiology; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D053244:Osteoprotegerin; D017698:Postmenopause / Q000097:blood* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D004966:Estrogens, Conjugated (USP); D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D017258:Medroxyprogesterone Acetate