Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass.
BACKGROUND
Arzoxifene, a benzothiophene estrogen agonist/antagonist, is being developed for prevention and treatment of osteoporosis and for risk reduction of invasive breast cancer in postmenopausal women.


METHODS
The effects of arzoxifene 20 mg/d on bone mineral density (BMD), uterine safety, and overall safety were studied in the FOUNDATION study, a 2-yr randomized, placebo-controlled trial including 331 postmenopausal women with normal to low bone mass.


RESULTS
Compared to placebo, arzoxifene significantly increased lumbar spine (+2.9%) and total hip (+2.2%) BMD. Arzoxifene decreased biochemical markers of bone metabolism compared to placebo. Changes in breast density were neutral or slightly decreased in the arzoxifene vs. placebo group. There was no evidence of endometrial hyperplasia or carcinoma in the arzoxifene group as assessed by central review of baseline and follow-up endometrial biopsies. There was no significant change between the groups in endometrial thickness assessed by transvaginal ultrasound. The incidence of uterine polyps and vaginal bleeding was not significantly different between the groups. Vulvovaginal mycotic infection was the only adverse event significantly increased in the arzoxifene vs. placebo group. Hot flushes were not significantly different between the groups.


CONCLUSIONS
In postmenopausal women with normal to low bone mass, arzoxifene 20 mg/d increased BMD at the spine and hip and had a neutral effect on the uterus and endometrium.
Bethesda Health Research Center, Bone Health Center of Bethesda, Maryland 20892, USA. mbolognese@erols.com
M
M
Bolognese
J H
JH
Krege
W H
WH
Utian
R
R
Feldman
S
S
Broy
D L
DL
Meats
J
J
Alam
M
M
Lakshmanan
M
M
Omizo
D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010919:Placebos; D017698:Postmenopause / Q000187:drug effects*; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010880:Piperidines; D010919:Placebos; D013876:Thiophenes; C115121:LY 353381