 |
|
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
C. Conrad Johnston, Jr, MD;
Nina H. Bjarnason, MD;
Fredric J. Cohen, MD;
Aarti Shah, PhD;
Robert Lindsay, MD;
Bruce H. Mitlak, MD;
William Huster, PhD;
Michael W. Draper, MD, PhD;
Kristine D. Harper, MD;
Hunter Heath III, MD;
Carlo Gennari, MD;
Claus Christiansen, MD, PhD;
Claude D. Arnaud, MD;
Pierre D. Delmas, MD, PhD
Arch Intern Med. 2000;160:3444-3450.
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.
From the Department of Medicine, Division of Endocrinology, Indiana University, Indianapolis (Dr Johnston); Center for Clinical and Basic Research, Ballerup, Denmark (Drs Bjarnason and Christiansen); Eli Lilly and Company, Indianapolis (Drs Cohen, Shah, Mitlak, Huster, and Draper); Helen Hayes Hospital, Clinical Research Center, West Haverstraw, NY (Dr Lindsay); Duke University Medical Center, Durham, NC (Dr Harper); University of Utah School of Medicine, Salt Lake City (Dr Heath); University of Siena, University Hospital of Siena, Siena, Italy (Dr Gennari); University of California, San Francisco (Dr Arnaud); and Hôpital Edouard Herriot and INSERM Research Unit, Lyon, France (Dr Delmas). Drs Cohen, Shah, Mitlak, Huster, Draper, Harper, and Heath are employees and stockholders of Eli Lilly and Co, Indianapolis. Drs Arnaud and Delmas have received honoraria from Eli Lilly Corporation and performed clinical trials of raloxifene supported by Eli Lilly. Dr Cohen is now with R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis
MacLean et al.
ANN INTERN MED 2008;148:197-213.
ABSTRACT
| FULL TEXT
Effect of Raloxifene on Bone Mineral Density in Premenopausal Women at Increased Risk of Breast Cancer
Eng-Wong et al.
J. Clin. Endocrinol. Metab. 2006;91:3941-3946.
ABSTRACT
| FULL TEXT
Osteoporosis
Obstet Gynecol 2004;104:66S-76S.
FULL TEXT
A Comparison of the Effects of Raloxifene and Conjugated Equine Estrogen on Bone and Lipids in Healthy Postmenopausal Women
Reid et al.
Arch Intern Med 2004;164:871-879.
ABSTRACT
| FULL TEXT
Long-Term Treatment of Lasofoxifene Preserves Bone Mass and Bone Strength and Does Not Adversely Affect the Uterus in Ovariectomized Rats
Ke et al.
Endocrinology 2004;145:1996-2005.
ABSTRACT
| FULL TEXT
Osteoporosis guidelines
Yendt
CMAJ 2003;168:1644-1644.
FULL TEXT
Osteoporosis guidelines
Brown
CMAJ 2003;168:1645-1646.
FULL TEXT
Selective Estrogen-Receptor Modulators -- Mechanisms of Action and Application to Clinical Practice
Riggs and Hartmann
NEJM 2003;348:618-629.
FULL TEXT
Raloxifene Administration in Women Treated with Gonadotropin-Releasing Hormone Agonist for Uterine Leiomyomas: Effects on Bone Metabolism
Palomba et al.
J. Clin. Endocrinol. Metab. 2002;87:4476-4481.
ABSTRACT
| FULL TEXT
The Effect of Raloxifene on Glyco-Insulinemic Homeostasis in Healthy Postmenopausal Women: A Randomized Placebo-Controlled Study
Cucinelli et al.
J. Clin. Endocrinol. Metab. 2002;87:4186-4192.
ABSTRACT
| FULL TEXT
American Society of Clinical Oncology Technology Assessment of Pharmacologic Interventions for Breast Cancer Risk Reduction Including Tamoxifen, Raloxifene, and Aromatase Inhibition
Chlebowski et al.
JCO 2002;20:3328-3343.
ABSTRACT
| FULL TEXT
Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis
Johnell et al.
J. Clin. Endocrinol. Metab. 2002;87:985-992.
ABSTRACT
| FULL TEXT
Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy
Simpson and Dowsett
Recent Prog Horm Res 2002;57:317-338.
ABSTRACT
| FULL TEXT
Effects of Long-Term Use of Raloxifene, a Selective Estrogen Receptor Modulator, on Thyroid Function Test Profiles
Hsu et al.
Clin. Chem. 2001;47:1865-1867.
FULL TEXT
Raloxifene Effect on Frequency of Surgery for Pelvic Floor Relaxation
Goldstein et al.
Obstet Gynecol 2001;98:91-96.
ABSTRACT
| FULL TEXT
|
