A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.
OBJECTIVE
We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis.


METHODS
A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group.


RESULTS
During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo.


CONCLUSIONS
Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.
Chesnut
C H
CH
University of Washington (CHC), Seattle, Washington, USA.
Silverman
S
S
Andriano
K
K
Genant
H
H
Gimona
A
A
Harris
S
S
Kiel
D
D
LeBoff
M
M
Maricic
M
M
Miller
P
P
Moniz
C
C
Peacock
M
M
Richardson
P
P
Watts
N
N
Baylink
D
D
D000368:Aged; D000704:Analysis of Variance; D015519:Bone Density / Q000187:drug effects*; D002116:Calcitonin / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008875:Middle Aged; D009296:Nasal Cavity; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D012016:Reference Values; D055502:Secondary Prevention; D016103:Spinal Fractures / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
C028815:salmon calcitonin; D002116:Calcitonin