Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.
BACKGROUND
Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures.


OBJECTIVE
To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures.


METHODS
Randomized, blinded, placebo-controlled trial.


METHODS
Eleven community-based clinical research centers.


METHODS
Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later).


METHODS
All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial.


METHODS
Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry.


RESULTS
Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects.


CONCLUSIONS
In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.
Cummings
S R
SR
Department of Epidemiology and Biostatistics, University of California, San Francisco 94105, USA. scummings@psg.ucsf.edu
Black
D M
DM
Thompson
D E
DE
Applegate
W B
WB
Barrett-Connor
E
E
Musliner
T A
TA
Palermo
L
L
Prineas
R
R
Rubin
S M
SM
Scott
J C
JC
Vogt
T
T
Wallace
R
R
Yates
A J
AJ
LaCroix
A Z
AZ
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use*; D015519:Bone Density; D002118:Calcium / Q000008:administration & dosage; D002762:Cholecalciferol / Q000008:administration & dosage; D019587:Dietary Supplements; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000473:pathology; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D012306:Risk; D016103:Spinal Fractures / Q000517:prevention & control; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology
D002762:Cholecalciferol; D002118:Calcium; D019386:Alendronate