Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial.
BACKGROUND
Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women.


OBJECTIVE
To determine whether HRT increases bone mineral density (BMD) in frail elderly women.


METHODS
Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000.


METHODS
Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty.


METHODS
Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months.


METHODS
The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover.


RESULTS
Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%).


CONCLUSIONS
In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.
Villareal
D T
DT
Division of Geriatrics and Gerontology, Washington University School of Medicine, 4488 Forest Park Blvd, St Louis, MO 63108, USA. dvillare@im.wustl.edu
Binder
E F
EF
Williams
D B
DB
Schechtman
K B
KB
Yarasheski
K E
KE
Kohrt
W M
WM
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004032:Diet; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D005269:Femur; D016330:Frail Elderly; D006615:Hip; D006801:Humans; D008159:Lumbar Vertebrae; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D010455:Peptides / Q000652:urine
D024042:Collagen Type I; D004966:Estrogens, Conjugated (USP); D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D017258:Medroxyprogesterone Acetate; D000469:Alkaline Phosphatase