Changes in bone density and turnover after alendronate or estrogen withdrawal.
OBJECTIVE
To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin.


METHODS
In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59 years were assigned to receive alendronate, placebo, or open-label estrogen-progestin (conjugated equine estrogens plus medroxyprogesterone acetate or a cyclic regimen of 17 beta-estradiol, norethisterone acetate and estradiol). Of the original women, one third after year 2 and one third after year 4 were switched from alendronate to placebo, while remaining blinded to treatment assignment. The women taking estrogen-progestin in years 1 to 4 were followed off therapy in years 5 and 6. BMD at the lumbar spine and hip and biochemical markers of bone turnover were measured.


RESULTS
The treatment groups described in the current report represent 860 women at baseline; 481 women entered year 5, and 430 completed 6 years. BMD steadily decreased in the placebo group during all 6 years. In contrast, spine and hip BMD increased during the first 4 years in the groups receiving daily continuous alendronate 5 mg and estrogen-progestin. During years 5 and 6, BMD decreased at the lumbar spine -2.42% (95% CI = -4.10, -0.74) and total hip -1.09% (-2.60, 0.41) in the group previously treated with alendronate 5 mg for 4 years. In comparison, large BMD decreases were observed at the spine [-7.69% (-8.96, -6.41)] and total hip [-5.16% (-6.30, -4.01)] among women who had received estrogen-progestin for 4 years.


CONCLUSIONS
Alendronate produces greater residual skeletal effects than estrogen-progestin after therapy discontinuation.
Wasnich
Richard D
RD
Radiant Research-Honolulu, Honolulu, HI 96814, USA. richardwasnich@radiantresearch.com
Bagger
Yu Z
YZ
Hosking
David J
DJ
McClung
Michael R
MR
Wu
Mei
M
Mantz
Ann Marie
AM
Yates
John J
JJ
Ross
Philip D
PD
Alexandersen
Peter
P
Ravn
Pernille
P
Christiansen
Claus
C
Santora
Arthur C
AC
D000368:Aged; D019386:Alendronate / Q000008:administration & dosage*; D015519:Bone Density; D016723:Bone Remodeling; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D004966:Estrogens, Conjugated (USP); D004958:Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone; D019386:Alendronate