Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene.
OBJECTIVE
Osteoporosis is a significant health problem in postmenopausal women. Consequently, new and effective therapies are being sought to preserve bone mass and prevent osteoporosis in this population of women. The objective of this study was to compare the effects of lasofoxifene with raloxifene and placebo on indices of bone health in postmenopausal women.


METHODS
A randomized, double-blind, placebo- and active treatment-controlled study of 2 years duration was conducted. Women included 410 postmenopausal women aged 47 to 74 years. The four treatment groups were: lasofoxifene 0.25 mg/day, or 1.0 mg/day, raloxifene 60 mg/day, or placebo daily. All women received daily calcium and vitamin D supplements. The primary endpoint was percent change from baseline to 2 years in lumbar spine bone mineral density (BMD) in all women having baseline and at least one follow-up bone density measurement. Total hip BMD, biochemical markers of bone turnover, low-density lipoprotein cholesterol, and safety were also evaluated in all women.


RESULTS
Both doses of lasofoxifene significantly increased lumbar spine BMD compared with raloxifene (P < or = 0.05) and with placebo treatment (P < or = 0.05). Least squares mean increases (95% CI) from baseline in lumbar spine BMD, compared with placebo, were 3.6% (1.9, 5.2) for lasofoxifene 0.25 mg/day, 3.9% (2.4, 5.5) for lasofoxifene 1.0 mg/day, and 1.7% (0.3, 3.0) for raloxifene. The two doses of lasofoxifene and raloxifene were equally effective at increasing total hip BMD. Lasofoxifene and raloxifene significantly reduced the levels of biochemical markers of bone turnover compared with placebo. In general, the effects of lasofoxifene were greater than the responses to raloxifene. At 2 years, lasofoxifene significantly (P < or = 0.05) reduced low-density lipoprotein cholesterol levels by 20.6% and 19.7% with 0.25 mg/day and 1 mg/day, respectively, compared with raloxifene (12.1%) and placebo (3.2%). Lasofoxifene and raloxifene had a similar adverse event profile with low rate of discontinuations due to adverse events.


CONCLUSIONS
Lasofoxifene may be an effective and well-tolerated treatment option for the prevention of bone loss in postmenopausal women.
McClung
Michael R
MR
Oregon Osteoporosis Center, Portland, OR 97213, USA. mmcclung@orost.com
Siris
Ethel
E
Cummings
Steve
S
Bolognese
Michael
M
Ettinger
Mark
M
Moffett
Alfred
A
Emkey
Ronald
R
Day
Wesley
W
Somayaji
Veena
V
Lee
Andrew
A
D000368:Aged; D000990:Antithrombin III; D001053:Apolipoproteins / Q000097:blood; D015519:Bone Density; D001862:Bone Resorption; D002097:C-Reactive Protein; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005340:Fibrinogen; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D001053:Apolipoproteins; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene; D020849:Raloxifene Hydrochloride; D000990:Antithrombin III; D005340:Fibrinogen; D002097:C-Reactive Protein; D002784:Cholesterol