Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial.
BACKGROUND
Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss.


OBJECTIVE
To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued.


METHODS
Randomized, controlled trial.


METHODS
United States and Europe.


METHODS
1609 postmenopausal women 45 to 59 years of age.


METHODS
Participants were randomly assigned to receive oral alendronate, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen-progestin. Women in the alendronate groups received alendronate for the first 2 years of the study. Treatment was then continued without change or replaced with placebo for the last 2 years of the study.


METHODS
Annual measurement of bone mineral density.


RESULTS
By year 4, the bone mineral density of participants in the placebo group had decreased by 1% to 6% (P < 0.001). Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine (mean change [+/-SE], 3.8%+/-0.3%), hip (mean, 2.9%+/-0.2%), and total body (mean, 0.9%+/-0.2%) (P < 0.001 overall). By year 4, bone mineral density at most skeletal sites was greater in participants who switched from alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater.


CONCLUSIONS
Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after alendronate therapy was stopped; however, continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo.
Ravn
P
P
Center for Clinical and Basic Research, Ballerup, Denmark.
Bidstrup
M
M
Wasnich
R D
RD
Davis
J W
JW
McClung
M R
MR
Balske
A
A
Coupland
C
C
Sahota
O
O
Kaur
A
A
Daley
M
M
Cizza
G
G
D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D011372:Progestins / Q000009:adverse effects / Q000627:therapeutic use*
D004967:Estrogens; D011372:Progestins; D019386:Alendronate