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      The association between circulating IGF1, IGFBP3, and calcium: results from NHANES III

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          Abstract

          Background

          Despite mounting evidence linking both calcium and IGF1, there is a lack of studies investigating any association between circulating levels of IGF1 and serum calcium.

          Methods

          Serum calcium, IGF1, and IGF-binding protein 3 (IGFBP3) were measured for 5368 participants in NHANES III. We calculated multivariable-adjusted geometric means of serum concentrations of IGF1, IGFBP3, and IGF1/IGFBP3 by categories of calcium (lowest 5% (<1.16 mmol/l), mid 90%, and top 5% (≥1.31 mmol/l)). We also performed stratified analyses by sex, age, ethnicity, BMI, serum levels of vitamin D, and bone mineral density (BMD).

          Results

          Overall, we found that circulating calcium was positively associated with circulating levels of IGF1 and IGFBP3, but not their molar ratio (i.e., geometric mean of IGF1 by increasing calcium categories: 237.63, 246.51, and 264.22 ng/nl; P trend: 0.43; P first vs third category: 0.01). In particular, these associations were observed in women, people aged <60, non-Hispanic whites, those with vitamin D levels above the mean, and those with low BMD. In contrast, there was an inverse association with the molar ratio for those with BMI ≥30 kg/m 2.

          Conclusion

          We found an overall positive association between circulating levels of IGF1 and IGFBP3 and serum calcium. However, stratification by potential effect-modifiers did not support all suggested hypotheses. Our findings provide more insight into the interplay between calcium and IGF1, which in the future can be investigated in larger observational studies allowing for additional stratifications based on a combination of the different effect-modifiers investigated here.

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          Most cited references37

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          Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force.

          Vitamin and mineral supplements are commonly used to prevent chronic diseases. To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. Dual quality assessments and data abstraction. Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. Agency for Healthcare Research and Quality.
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            Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

            Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.
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              Vitamin D and bone health.

              Vitamin D plays an essential role in maintaining a healthy mineralized skeleton for most land vertebrates including humans. Sunlight causes the photoproduction of vitamin D3 in the skin. Once formed, vitamin D3 is metabolized sequentially in the liver and kidney to 1,25-dihydroxyvitamin D. The major biological function of 1,25-dihydroxyvitamin D is to keep the serum calcium and phosphorus concentrations within the normal range to maintain essential cellular functions and to promote mineralization of the skeleton. Most foods do not contain any vitamin D. Foods fortified with vitamin D have a variable amount present and cannot be depended on as a sole source of vitamin D nutrition. Exposure to sunlight provides most humans with their vitamin D requirement. Aging, sunscreen use and the change in the zenith angle of the sun can dramatically affect the cutaneous production of vitamin D3. Vitamin D insufficiency and vitamin D deficiency is now being recognized as a major cause of metabolic bone disease in the elderly. Vitamin D deficiency not only causes osteomalacia but can exacerbate osteoporosis. It is generally accepted that an increase in calcium intake to 1000-1500 mg/d along with an adequate source of vitamin D of at least 400 IU/d is important for maintaining good bone health.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                3 August 2015
                1 September 2015
                : 4
                : 3
                : 187-195
                Affiliations
                [1]Cancer Epidemiology Group, Division of Cancer Studies , King's College London , London, UK
                [1 ]Division of Chronic Disease Epidemiology , Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich , Hirschengraben 848001, Zurich, Switzerland
                Author notes
                Correspondence should be addressed to S Rohrmann Email: sabine.rohrmann@ 123456ifspm.uzh.ch
                Article
                EC150039
                10.1530/EC-15-0039
                4547399
                26304028
                40fafa08-2ae7-41a1-8e9f-6d579582becb
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License.

                History
                : 10 July 2015
                : 3 August 2015
                Categories
                Research

                igf-1,igfbp3,calcium,cross-sectional
                igf-1, igfbp3, calcium, cross-sectional

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