Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention trial.
OBJECTIVE
To evaluate the effect of alendronate on the occurrence rate of multiple svmptomatic fractures and on the risk of multiple symptomatic fractures (likelihood of having more than one fracture diagnosed because of the symptoms the fractures caused over the study period) among women with osteoporosis.


METHODS
Primary analysis of data from a randomized, placebo-controlled, double-blind trial.


METHODS
Eleven community-based clinical research centers.


METHODS
Subset of women enrolled in the Fracture Intervention Trial: aged 55 to 81 and having at least one morphometric vertebral fracture at baseline (n=2,027) or having no vertebral fracture but meeting prevailing World Health Organization bone mineral density criteria for osteoporosis (T-score < or =2.5 at the femoral neck)(n = 1,631).


METHODS
All participants reporting calcium intake of 1,000 mg/day or less received a supplement of 500 mg calcium and 250 IU cholecalciferol. Participants were randomly assigned to placebo or alendronate sodium (5 mg/day for 2 years and 10 mg/day for the remainder of the study). Average total follow-up was 4.3 years.


METHODS
Symptomatic fractures were diagnosed by personal physicians and confirmed by review of radiological data by an expert committee blinded to treatment assignments.


RESULTS
Eighty-six of 1,817 women receiving placebo experienced multiple symptomatic fractures during the follow-up period, compared with 51 of 1,841 receiving alendronate. Reduction of risk for multiple symptomatic fractures combined was 42% (relative risk (RR) = 0.58, 95% confidence interval (CI) = 0.41, 0.81) and for multiple symptomatic vertebral fractures was 84% (RR = 0.16,95% Cl = 0.05, 0.42). Cumulative incidence curves showed divergence after as little as 3 months of treatment, with a statistically significant (P = .044) reduction at 6 months for multiple symptomatic vertebral fractures. When all fractures over the follow-up period were included, the occurrence rates of all symptomatic fractures and symptomatic vertebral fractures were 34% and 63% lower, respectively, with alendronate than with placebo. These reductions were sustained during the follow-up period. All reductions in risk were consistent across predefined subgroups: age (<75 vs > or =75), morphometric vertebral fracture(present vs absent), prior clinical fracture since age 45 (yes vs no), and whether the subject had fallen in the 12 months before randomization.


CONCLUSIONS
These data demonstrate that treatment with alendronate reduces the risk of multiple symptomatic fractures during a treatment period averaging 4.3 years. The reductions were consistent across prespecified sub-groups. This effect is evident early in treatment and is sustained.
Levis
Silvina
S
Department of Medicine, Osteoporosis Center, University of Miami School of Medicine, 1475 Northwest 12 Avenue, Suite 407, Miami, FL 33101, USA. slevis@med.miami.edu
Quandt
Sara A
SA
Thompson
Desmond
D
Scott
Jean
J
Schneider
Diane L
DL
Ross
Philip D
PD
Black
Dennis
D
Suryawanshi
Shailaja
S
Hochberg
Marc
M
Yates
John
J
D000368:Aged; D019386:Alendronate / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D009104:Multiple Trauma / Q000453:epidemiology / Q000517:prevention & control; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
D019386:Alendronate