title: Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial.
abstract: BACKGROUND
  Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis, but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown.
  
  
  OBJECTIVE
  To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe, and how they compare with monotherapy in community-dwelling elderly women.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, clinical trial.
  
  
  METHODS
  Five hundred seventy-three community-dwelling women age 65 years or older were screened: 485 completed screening and 373 (aged 65 to 90 years) were randomized following a 3-month, open-label, run-in phase with hormone replacement and alendronate placebo. The trial was conducted at a single academic US medical center from January 1996 to May 2001.
  
  
  METHODS
  Participants were randomly assigned in a 2 x 2 factorial design to receive hormone replacement (conjugated equine estrogen, 0.625 mg/d, with or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10 mg daily, both agents, or neither. All participants received calcium and vitamin D supplements.
  
  
  METHODS
  Annualized change in bone mineral density of the hip and spine and occurrence of adverse events.
  
  
  RESULTS
  Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy, with mean (SD) increases of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean (SD) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; P<.05, respectively), and alendronate resulted in more responders to therapy. All therapies were well tolerated and participant retention was 90% at 3 years.
  
  
  CONCLUSIONS
  Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort. Alendronate was superior to hormone replacement, and combination therapy was superior to either therapy alone. Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy.
authors.affiliation: Division of Endocrinology and Metabolism and Division of Geriatric Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pa, USA. griffithsd@msx.dept-med.pitt.edu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Greenspan
authors.forename: Neil M
authors.initials: NM
authors.lastname: Resnick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D015519:Bone Density; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D045167:Progesterone Congeners / Q000627:therapeutic use*
chemical_list: D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D017258:Medroxyprogesterone Acetate; D019386:Alendronate