Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials.
BACKGROUND
In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women.


METHODS
A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels.


RESULTS
Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo).


CONCLUSIONS
Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.
Johnston
C C
CC
Indiana University School of Medicine, Emerson Hall Room 421, 545 Barnhill Dr, Indianapolis, IN 46202, USA.
Bjarnason
N H
NH
Cohen
F J
FJ
Shah
A
A
Lindsay
R
R
Mitlak
B H
BH
Huster
W
W
Draper
M W
MW
Harper
K D
KD
Heath
H
H
Gennari
C
C
Christiansen
C
C
Arnaud
C D
CD
Delmas
P D
PD
D015519:Bone Density / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride