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      A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial.

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          Abstract

          Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, for example, calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a 3-month intervention using a calcium-collagen chelate (CC) dietary supplement was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. This study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for 12 months. Total body, lumbar, and hip BMD were evaluated at baseline, 6 and 12 months using dual-energy X-ray absorptiometry. Blood was collected at baseline, 6 and 12 months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons and multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at 12 months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P=.026, P=.035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) (P<.05), and higher bone-specific alkaline phosphatase/TRAP5b ratio (P<.05) than control at 6 months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women.

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          Pathogenesis of osteoporosis: concepts, conflicts, and prospects.

          Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.
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            Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis.

            R Pacifici (1996)
            In summary, available data demonstrate that IL-1 and TNF are the causative agents underlying the bone loss induced by estrogen deficiency. Indeed, these factors are produced in bone and the bone marrow, released in larger amounts from cells of estrogen-deficient subjects, and indispensable for reproducing the effects of estrogen deficiency in bone. These observations support the hypothesis that the bone sparing effect of estrogen is due to the ability of the hormone to block osteoclastogenesis, the activation of mature osteoclasts and, as recently demonstrated, the rate of apoptotic osteoclast death. Although IL-1 and TNF play a prominent causal role in these events, the bone-sparing effect of estrogen is mediated by numerous cytokines which, by simultaneously stimulating multiple target cells, induce effects that are not accounted for by any one single factor (Fig. 2). The ability of estrogen to regulate some, but not all, the cytokines involved in this process is not inconsistent with this hypothesis because cytokines have potent synergistic effects. Thus, a considerable increase in bone resorption may result from a relatively small increase in the concentration of only a few of the bone-resorbing factors present in the bone microenvironment. This concept is best illustrated by the study of Miyaura et al. demonstrating that the concentrations of either IL-1, IL-6, IL-6 receptor, or prostaglandins detected in the bone marrow of OVX mice are insufficient to account for the increased bone resorption caused by estrogen withdrawal. In contrast, the increase in bone resorption induced by OVX can be explained by the cumulative effects of these cytokines. Thus, a better understanding of the cooperative effects of cytokines and a recognition that the contribution of individual cytokines to postmenopausal bone loss varies with the passage of time after menopause are necessary to fully understand the mechanism of action of estrogen in bone. Although the relevance of individual bone-targeting cytokines in species specific, the development of transgenic mice with activatable or deactivatable promoters is likely to result in a further clarification of the integrated action of estrogen-regulated cytokines in human bone cells and lay the foundations for the use of cytokine inhibitors in the treatment of postmenopausal osteoporosis.
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              Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates.

              In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.
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                Author and article information

                Journal
                J Med Food
                Journal of medicinal food
                Mary Ann Liebert Inc
                1557-7600
                1096-620X
                Mar 2015
                : 18
                : 3
                Affiliations
                [1 ] 1 Department of Nutrition, Food and Exercise Sciences, Florida State University , Tallahassee, Florida, USA .
                Article
                10.1089/jmf.2014.0100
                25314004
                c687c239-2063-4489-99a8-801d2f0231f0
                History

                collagen hydrolysate,estrogen,menopause,osteoporosis,sclerostin

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