Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.
BACKGROUND
Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis.


OBJECTIVE
To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis.


METHODS
Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998.


METHODS
Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low.


METHODS
Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry.


RESULTS
The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo.


CONCLUSIONS
These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.
Harris
S T
ST
University of California, San Francisco 94117-3608, USA.
Watts
N B
NB
Genant
H K
HK
McKeever
C D
CD
Hangartner
T
T
Keller
M
M
Chesnut
C H
CH
Brown
J
J
Eriksen
E F
EF
Hoseyni
M S
MS
Axelrod
D W
DW
Miller
P D
PD
D000368:Aged; D000704:Analysis of Variance; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D016016:Proportional Hazards Models; D011859:Radiography; D000068296:Risedronic Acid; D012306:Risk; D016103:Spinal Fractures / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control
D000068296:Risedronic Acid; D012968:Etidronic Acid