Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women.
OBJECTIVE
To evaluate the efficacy of the tissue-selective estrogen complex, bazedoxifene/conjugated estrogens (BZA/CE), for postmenopausal osteoporosis prevention.


METHODS
Multicenter, randomized, double-blind, placebo- and active-controlled, phase 3 trial (Selective estrogen Menopause And Response to Therapy [SMART]-1).


METHODS
Outpatient clinical study.


METHODS
Women (n = 3,397) more than 5 years and 1-5 years postmenopause were enrolled in the Osteoporosis Prevention I and II Substudies, respectively.


METHODS
Single tablets of BZA (10, 20, or 40 mg) each with CE (0.625 or 0.45 mg), raloxifene (60 mg), or a placebo taken daily for 2 years.


METHODS
The primary outcome for both substudies was change in bone mineral density of the lumbar spine; bone mineral density was also measured at the hip.


RESULTS
In both substudies, bone mineral density increased significantly more with all BZA/CE doses compared with placebo at the lumbar spine and total hip, and for most BZA/CE doses compared with raloxifene at the lumbar spine. Osteocalcin and N-telopeptide significantly decreased with all BZA/CE doses vs. placebo and most BZA/CE doses vs. raloxifene.


CONCLUSIONS
BZA/CE combinations decreased bone turnover and bone loss in postmenopausal women at increased risk for osteoporosis.
Lindsay
Robert
R
Department of Medicine, Helen Hayes Hospital, West Haverstraw, New York, New York, and Columbia University, New York, New York. Electronic address: lindsayr@helenhayeshosp.org.
Gallagher
J Christopher
JC
Bone Metabolism Unit, Creighton University School of Medicine, Omaha, Nebraska.
Kagan
Risa
R
Foundation for Osteoporosis Research and Education, Oakland, California and East Bay Physicians Medical Group, Berkeley, California.
Pickar
James H
JH
Clinical Research and Development, Wyeth Research, Philadelphia, Pennsylvania.
Constantine
Ginger
G
Clinical Research and Development, Wyeth Research, Philadelphia, Pennsylvania.
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000453:epidemiology* / Q000517:prevention & control*; D010455:Peptides / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D024042:Collagen Type I; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D010455:Peptides; D020845:Selective Estrogen Receptor Modulators; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D020849:Raloxifene Hydrochloride; C447119:bazedoxifene