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

Chesnut, Charles H.; Silverman, Stuart; Andriano, Kim; Genant, Harry; Gimona, Alberto; Harris, Steven; Kiel, Douglas; LeBoff, Meryl; Maricic, Michael; Miller, Paul; Moniz, Caje; Peacock, Munro; Richardson, Peter; Watts, Nelson; Baylink, David

Affiliations

¹University of Washington, Seattle, Washington

²University of California, Los Angeles, West Lost Angeles Veterans Affairs, Beverly Hills, California Medical Center

³Novartis Pharmaceuticals, East Hanover, New Jersey

⁴Departments of Radiology and Medicine, University of California, San Francisco, San Francisco, California

⁵Novartis Pharma AG, Basel, Switzerland

⁶University of California, San Francisco, San Francisco, California

⁷Rhode Island Hospital, Providence, Rhode Island

⁸Brigham and Women’s Hospital, Boston, Massachusetts

⁹University of Arizona, Arizona Health Science Center, Tucson, Arizona

¹⁰Colorado Center for Bone Research, Lakewood, Colorado

¹¹King’s College Hospital, London, United Kingdom

¹²Indiana University Medical Center, Indianapolis, Indiana

¹³Emory Clinic, Atlanta, Georgia

¹⁴Jerry L. Pettis Veterans Hospital, Loma Linda, California

Abstract

Purpose: 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.

Subjects and 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.

Conclusion: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Links

DOI: 10.1016/S0002-9343(00)00490-3

PubMed: 10996576

WoS: 000089356600001

History

Received: 1999-11-8

Accepted: 2000-05-18

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