Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass.
The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with >or=1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P<0.001), with greater increases in the ALN group (each P<0.05). Similar numbers of women in each group had >or=1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P<0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports.


BACKGROUND
ClinicalTrials.gov Identifier NCT00035971.
Recker
Robert R
RR
Creighton University, Osteoporosis Research Center, 601 North 30th Street, Suite 5766, Omaha, NE 68131, USA. rrecker@creighton.edu
Kendler
David
D
Recknor
Christopher P
CP
Rooney
Theodore W
TW
Lewiecki
E Michael
EM
Utian
Wulf H
WH
Cauley
Jane A
JA
Lorraine
Joanne
J
Qu
Yongming
Y
Kulkarni
Pandurang M
PM
Gaich
Carol L
CL
Wong
Mayme
M
Plouffe
Leo
L
Stock
John L
JL
D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D020849:Raloxifene Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety
D050071:Bone Density Conservation Agents; D020849:Raloxifene Hydrochloride; D019386:Alendronate