title: The effects of selective estrogen receptor modulator treatment following hormone replacement therapy on elderly postmenopausal women with osteoporosis.
abstract: OBJECTIVE
  A comparison between the atheroprotective and osteoprotective effects of the selective estrogen receptor modulator (SERM) raloxifene and those of hormone replacement therapy (HRT) has not been made in elderly women.
  
  
  METHODS
  A randomized prospective controlled trial was performed in a cohort of 32 elderly Japanese women with osteoporosis receiving HRT (estriol plus medroxyprogesterone) for more than 1 year. In 16 randomly selected subjects, HRT was changed to raloxifene therapy (60mg/day, 71.4±3.4 years, SERM group). The other 16 patients were continued on HRT (71.8±2.9 years, HRT group). As a control group, 14 subjects were enrolled, did not take any medications and were age-matched to experimental patients (72.5±3.3 years, control group). Plasma lipids, TNFα, adiponectin, NO metabolites (NOx:NO2(-) and NO3(-)), cyclicGMP and bone-mineral density (BMD) were evaluated at baseline and at 26 and 52 weeks after enrollment.
  
  
  RESULTS
  SERM (Raloxifene) increased high-density-lipoprotein cholesterol levels and tended to decrease low-density-lipoprotein cholesterol levels (P=0.058) compared with baseline. Adiponectin, NOx and cGMP levels were significantly increased after 6 months compared with baseline or the HRT group. TNFα was decreased by raloxifene. In control subjects, no significant changes were observed in any of these markers. Bone-mineral density was higher at baseline in the raloxifene and HRT groups than in the control group, and BMD increased 12 months after baseline in the HRT and control group.
  
  
  CONCLUSIONS
  SERM improved BMD and endothelial function in elderly postmenopausal women with osteoporosis who had received HRT, and these effects were comparable to or slightly stronger than those of HRT. Changes in adiponectin and TNFα may underlie the improvements in endothelial function, such as NO signaling.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. hayashi@med.nagoya-u.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Hayashi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ina
authors.forename: Morihiko
authors.initials: M
authors.lastname: Maeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Nomura
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015519:Bone Density / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004964:Estriol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007564:Japan; D008525:Medroxyprogesterone / Q000627:therapeutic use; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy*; D017698:Postmenopause / Q000187:drug effects*; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D020845:Selective Estrogen Receptor Modulators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D004964:Estriol; D008525:Medroxyprogesterone