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      Does salmon calcitonin cause cancer? A review and meta-analysis

      review-article
      , , ,
      Osteoporosis International
      Springer London
      Cancer, Meta-analysis, Review, Salmon calcitonin

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          Abstract

          Recently an association between the use of calcitonin and cancer has been postulated. We reviewed the biological rationale and performed an additional analysis of historical data with respect to the possibility. An association cannot be excluded, but the relationship is weak and causality is unlikely. The purpose of the present study is to review the strength of association and likelihood of a causal relationship between use of calcitonin and cancer. We reviewed the evidence for this association, including the molecular signaling mechanisms of calcitonin, preclinical data, an “experiment of nature,” and the results of a previous meta-analysis which showed a weak association. We performed an additional meta-analysis to incorporate the data from a novel investigational oral formulation of salmon calcitonin. Review of the literature did not identify a cellular signaling mechanism of action which might account for a causal relationship or toxicologic or postmarketing data to support the thesis. Additional clinical results incorporated into previous meta-analyses weakened but did not completely negate the possibility of association. A causal association between calcitonin use and malignancy is unlikely, as there is little biological plausibility. The preponderance of nonclinical and clinical evidence also does not favor a causal relationship.

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          Most cited references24

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          Continuing bisphosphonate treatment for osteoporosis--for whom and for how long?

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

            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. 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. 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. Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.
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              Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002-2012.

              Bisphosphonates have been widely prescribed to postmenopausal women for treatment and prevention of osteoporosis. Given a background of reports of recent safety problems, questions about optimal duration of use, and the patent expiration of Fosamax in February 2008, we accessed data from pharmaceutical marketing research databases to describe trends in dispensed prescriptions and sales of oral bisphosphonates, characteristics of patients and prescribers, and sales of intravenous bisphosphonates for osteoporosis treatment. An estimated 21.3million prescriptions for oral bisphosphonates were dispensed in U.S. retail pharmacies in 2002 that increased 46% to a peak of 31.0million in 2007 and 2008, and declined by 53% in a four year-period to 14.7million in 2012. Sales data (number of packages sold in all settings of care) showed parallel trends (66% increase from 2002 through 2007 and 51% decrease from 2007 through 2012). Similarly, intravenous bisphosphonate sales for osteoporosis treatment grew 3.8-fold from 149.5 thousand packages in 2007 to 561.6 thousand in 2010, followed by a 22% decrease in 2012. Data from an ongoing monthly office-based survey indicated physicians mentioned oral bisphosphonates primarily in visits of older aged Caucasian women with lower body mass for osteoporosis. Frequencies of oral bisphosphonate mentions increased between 2002 and 2012 in visits of Asians and for osteopenia diagnoses. These data indicate a substantial decline in prescriptions and sales of oral (since 2007-2008) and intravenous (since 2010) bisphosphonates for osteoporosis treatment in the United States. Reasons for, and implications of, the decline should be considered for future research.
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                Author and article information

                Contributors
                613-761-5000
                267.273.7942 , dkrause@tarsatherapeutics.com
                Journal
                Osteoporos Int
                Osteoporos Int
                Osteoporosis International
                Springer London (London )
                0937-941X
                1433-2965
                5 October 2015
                5 October 2015
                2016
                : 27
                : 13-19
                Affiliations
                [ ]University of Ottawa Heart Institute, Ottawa, Ontario Canada K1Y 4W7
                [ ]Fox Chase Cancer Institute, 333 Cottman Ave # 307, Philadelphia, USA
                [ ]Tarsa Therapeutics Inc, 8 Penn Center, 1628 JFK Blvd., Philadelphia, PA 19103 USA
                Author information
                http://orcid.org/0000-0002-5484-8563
                Article
                3339
                10.1007/s00198-015-3339-z
                4715844
                26438308
                f2b64428-8f5d-4340-8c60-0ae317b39a8d
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 27 July 2015
                : 24 September 2015
                Categories
                Review
                Custom metadata
                © International Osteoporosis Foundation and National Osteoporosis Foundation 2016

                Orthopedics
                cancer,meta-analysis,review,salmon calcitonin
                Orthopedics
                cancer, meta-analysis, review, salmon calcitonin

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