A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlle d study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with establishe d osteoporosis were randomly assigned to receive salmon calcitonin nasal sp ray (100, 200, or 400 IU) or placebo daily. All participants received eleme ntal calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures w ere assessed with lateral radiographs of the spine. The primary efficacy en dpoint was the risk of new vertebral fractures in the salmon calcitonin nas al spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radi ograph. A total of 783 women completed 3 years of treatment, and 511 comple ted 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% confi dence 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 vertebr al fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-I U (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly differen t from placebo. Lumbar spine bone mineral density increased significantly f rom baseline (1% to 1.5%, P <0.01) in all active treatment groups. Bone tur nover 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) an d by 14% in the 400-IU group (P <0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily signifi cantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis. Am J Med. 2000;109:267-276. (C) 2000 by Excerpta Medica, Inc.