The Mechanism of Dietary Protein Modulation of Bone Metabolism via Alterations in Members of the GH/IGF Axis

Author(s): Chen Lv, Songcai Liu, Jichao Xia, Lei Xu, Yunyun Cheng, Wenyue Li, Yu Zhang, Gang Wang, Wenzhen Wei, Hongyu Shi, Shan Huang, Nan Wang*, Linlin Hao*.

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Dietary protein intake as a critical regulatory factor of bone metabolism is a vital element to regulate nutritional status of mammals. Under the action of protease, dietary protein is digested into peptides and free amino acids (FAAs). Then, the metabolites are absorbed by enterocytes and metabolized in various organs of mammals. The dietary protein intake regulates bone metabolism generally via two aspects, dietary itself and signaling transduction. At the dietary level, different kinds of amino acids (AAs) of dietary protein may affect various protein metabolism of bone by regulating proteasome depending on proteolysis and protein synthesis. In addition, dietary protein from multiple sources such as animal, vegetal and healthcare products, presents distinct influences on bone metabolism via regulating calcium balance; At the cellular level, these products can regulate several biological functions via regulating signaling transduction. For example, the significant member of growth hormone/insulin-like growth factor (GH/IGF) axis can be regulated by dietary protein, which has an influence on bone metabolism through different approaches. This review mainly discusses the relationship between dietary protein and GH/IGF axis and illustrates the regulation of bone metabolism in mammals by dietary protein and its signaling transduction.

Keywords: Dietary protein, bone metabolism, growth hormone/insulin-like growth factors (GH/IGF) axis, signaling pathway, essential amino acids (EAAs), calcium balance.

Fox, P.F.; Uniacke-Lowe, T.; Mcsweeney, P.L.H.; O’Mahony, J.A. Dairy chemistry and biochemistry, 2nd ed; Springer: New York, 2015.
Anderson, G.H.; Luhovyy, B.; Akhavan, T.; Panahi, S.; Clemens, R.A.; Hernell, O.; Michaelsen, K.F. Milk proteins in the regulation of body weight, satiety, food intake and glycemia. Nestle Nutr. Workshop Ser., 2011, 67, 147-205.
Xiong, Y.L. 5–Muscle proteins. Proteins Food Process, 2004, 5, 100-122.
Coultate, T. Food proteins: Processing applications. Int. J. Food Sci. Technol., 2001, 36, 452-452.
Tanaka, N.; Aoyama, T.; Kimura, S.; Gonzalez, F.J. Targeting nuclear receptors for the treatment of fatty liver disease. Pharmacol. Ther., 2017, 179, 142-157.
Stayrook, K.R.; Bramlett, K.S.; Savkur, R.S.; Ficorilli, J.; Cook, T.; Christe, M.E.; Michael, L.F.; Burris, T.P. Regulation of carbohydrate metabolism by the farnesoid X receptor. Endocrinology, 2005, 146, 984-1074.
Gong, H.; Wang, X.; Wang, L.; Liu, Y.; Wang, J.; Lv, Q.; Pang, H.; Zhang, Q.; Wang, Z. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1. Mol. Med. Rep., 2017, 16, 787-793.
Elumalai, P.; Arunkumar, R.; Benson, C.S.; Sharmila, G.; Arunakaran, J. Nimbolide inhibits IGF-I-mediated PI3K/Akt and MAPK signalling in human breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem. Funct., 2014, 32, 476-484.
Manning, B.D.; Cantley, L.C. AKT/PKB signaling: Navigating downstream. Cell, 2007, 129, 1261-1334.
Zhang, M.; Zhang, P.; Liu, Y.; Zhou, Y. GSK3 inhibitor AR-A014418 promotes osteogenic differentiation of human adipose-derived stem cells via ERK and mTORC2/Akt signaling pathway. Biochem. Biophys. Res. Commun., 2017, 490, 182-188.
Ma, N.; Tian, Y.; Wu, Y.; Ma, X. Contributions of the interaction between dietary protein and gut microbiota to intestinal health. Curr. Protein Pept. Sci., 2017, 18, 795-808.
Naderi, N.; House, J.D.; Pouliot, Y. Scaling-up a process for the preparation of folate-enriched protein extracts from hen egg yolks. J. Food Eng., 2014, 141, 85-92.
Seyoum, E.; Selhub, J. Properties of food folates determined by stability and susceptibility to intestinal pteroylpolyglutamate hydrolase action. J. Nutr., 1998, 128, 1956-1960.
Comerford, K.B.; Pasin, G. Emerging evidence for the importance of dietary protein source on glucoregulatory markers and type 2 diabetes: Different effects of dairy, meat, fish, egg, and plant protein foods. Nutrients, 2016, 8, 446-463.
Michelfelder, A.J. Soy: A complete source of protein. Am. Fam. Physician, 2009, 79, 43-47.
Young, V.R.; Pellett, P.L. Plant proteins in relation to human protein and amino acid nutrition. Am. J. Clin. Nutr., 1994, 59, 1203S-1212S.
Darby, M.K.; Loughead, J.L. Neonatal nutritional requirements and formula composition: A review. J. Obstet. Gynecol. Neonatal Nurs., 1996, 25, 209-225.
Marsh, K.; Möller, J.; Basarir, H.; Orfanos, P.; Detzel, P. The economic impact of lower protein infant formula for the children of overweight and obese mothers. Nutrients, 2016, 8, 18-30.
Chen, X.; Eslamfamc, S.; Fang, L.; Qiao, S.; Ma, X. Maintenance of gastrointestinal glucose homeostasis by the gut-brain axis. Curr. Protein Pept. Sci., 2017, 18, 541-547.
Samloff, I.M. Peptic ulcer: The many proteinases of aggression. Gastroenterology, 1989, 96, 586-680.
Hu, S.; Liu, H.; Qiao, S.; He, P.; Ma, X.; Lu, W. Development of immunoaffinity chromatographic method for isolating glycinin (11S) from soybean proteins. J. Agric. Food Chem., 2013, 61, 4406-4410.
Han, P.; Yin, J.; He, P.; Ma, X. Dose-effect study of lipoic acid supplementation on growth performance in a weaned rat model. J. Anim. Sci. Biotechnol., 2011, 2, 533-538.
Song, P.; Zhang, R.; Wang, X.; He, P.; Tan, L.; Ma, X. Dietary grape-seed procyanidins decreased postweaning diarrhea by modulating intestinal permeability and suppressing oxidative stress in rats. J. Agric. Food Chem., 2011, 59, 6227-6258.
Fordtran, J.S.; Jr, R.F. Stimulation of intestinal sodium absorption by sugars. Am. J. Clin. Nutr., 1971, 24, 503-506.
Chairoungdua, A.; Segawa, H.; Kim, J.Y.; Miyamoto, K.; Haga, H.; Fukui, Y.; Mizoguchi, K.; Ito, H.; Takeda, E.; Endou, H. Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein. J. Biol. Chem., 1999, 274, 28845-28852.
Fan, P.; Song, P.; Li, L.; Huang, C.; Chen, J.; Yang, W.; Qiao, S.; Wu, G.; Zhang, G.; Ma, X. Roles of biogenic amines in intestinal signaling proteins and its detection. Curr. Protein Pept. Sci., 2017, 18, 532-540.
Zarei, I.; Brown, D.G.; Nealon, N.J.; Ryan, E.P. Rice bran metabolome contains amino acids, vitamins & cofactors, and phytochemicals with medicinal and nutritional properties. Rice (N. Y.), 2017, 10, 24-44.
Pasiakos, S.M.; Martin, W.F.; Sharma, C.S.; Pikosky, M.A.; Gaine, P.C.; Bolster, D.R.; Bennett, B.T.; Rodriguez, N.R. Level of dietary protein intake affects glucose turnover in endurance-trained men. J. Int. Soc. Sports Nutr., 2011, 8, 20-23.
Hu, S.; Han, M.; Rezaei, A.; Li, D.; Wu, G.; Ma, X. L-arginine modulates glucose and lipid metabolism in obesity and diabetes. Curr. Protein Pept. Sci., 2017, 18, 599-608.
Gonciulea, A.R.; Sellmeyer, D.E. The effect of dietary protein source on serum lipids: Secondary data analysis from a randomized clinical trial. J. Clin. Lipidol., 2017, 11, 46-54.
Ma, X. Editorial: Signal proteins involved in glucose and lipid metabolism regulation. Curr. Protein Pept. Sci., 2017, 18, 524-524.
Wang, J.; Hong, Z.; Wu, L.; Ding, B.; Bi, Y.; Gu, Z.; Li, W. Dietary intake and cardiometabolic biomarkers in relation to insulin resistance and hypertension in a middle-aged and elderly population in Beijing, China. Appl. Physiol. Nutr. Metab., 2017, 42, 869-875.
Ginty, F. Dietary protein and bone health. Proc. Nutr. Soc., 2003, 62, 867-876.
van der Wielen, N.; Moughan, P.J.; Mensink, M. Amino acid absorption in the large intestine of humans and porcine models. J. Nutr., 2017, 147, 1493-1498.
Mcneil, N.I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr., 1984, 39, 338-379.
Cummings, J.H. The large intestine. Its role in mammalian nutrition and homeostasis. Q. Rev. Biol., 1981, 22, 896-901.
Hartman, J.W.; Tang, J.E.; Wilkinson, S.B.; Tarnopolsky, M.A.; Lawrence, R.L.; Fullerton, A.V.; Phillips, S.M. Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. Am. J. Clin. Nutr., 2007, 86, 373-453.
Tang, J.E.; Moore Drkujbida, G.W. Ingestion of effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J. Appl. Physiol., 2009, 107, 987-992.
Gilbert, E.R.; Li, H.; Emmerson, D.A.; Jr, W.K.; Wong, E.A. Dietary protein composition influences abundance of peptide and amino acid transporter messenger ribonucleic acid in the small intestine of 2 lines of broiler chicks. Poult. Sci., 2010, 89, 1663-1738.
Gilbert, E.R.; Li, H.; Emmerson, D.A.; Webb, K.E., Jr; Wong, E.A. Dietary protein quality and feed restriction influence abundance of nutrient transporter mRNA in the small intestine of broiler chicks. J. Nutr., 2008, 138, 262-332.
Paddonjones, D.; Sheffieldmoore, M.; Aarsland, A.; Wolfe, R.R.; Ferrando, A.A. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am. J. Physiol. Endocrinol. Metab., 2005, 288, E761-E767.
Ohlsson, C.; Mohan, S.K. The role of liver-derived insulin-like growth factor-I. Endocr. Rev., 2009, 30, 494-535.
Isley, W.L.; Underwood, L.E.; Clemmons, D.R. Dietary components that regulate serum somatomedin-C concentrations in humans. J. Clin. Invest., 1983, 71, 175-256.
Campbell, R.G.; Johnson, R.J.; King, R.H.; Taverner, M.R.; Meisinger, D.J. Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs. J. Anim. Sci., 1990, 68, 3217-3241.
Thissen, J.P.; Triest, S.; Moatsstaats, B.M.; Underwood, L.E.; Mauerhoff, T.; Maiter, D.; Ketelslegers, J.M. Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations during dietary protein restriction. Endocrinology, 1991, 129, 429-463.
Straus, D.S.; Takemoto, C.D. Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol. Endocrinol., 1990, 4, 91-100.
Vandehaar, M.J.; Moatsstaats, B.M.; Davenport, M.L.; Walker, J.L.; Ketelslegers, J.M.; Sharma, B.K.; Underwood, L.E. Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein-restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle. J. Endocrinol., 1991, 130, 305-316.
Lowe, W.L. Jr., Adamo, M.; Werner, H.; Roberts, C.T.; Jr., Leroith, D. Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding. J. Clin. Invest., 1989, 84, 619-644.
Ketelslegers, J.M.; Maiter, D.; Maes, M.; Underwood, L.E.; Thissen, J.P. Nutritional regulation of insulin-like growth factor-I. Metab. Clin. Exp., 1995, 44, 50-56.
Thissen, J.P.; Ketelslegers, J.M.; Underwood, L.E. Nutritional regulation of the insulin-like growth factors. Endocr. Rev., 1994, 15, 80-101.
Funaba, M.; Kagiyama, K.; Iriki, T.; Abe, M.; Onodera, R.; Itabashi, H.; Ushida, K.; Yano, H.; Sasaki, Y. Rumen Microbes & Digestive Physiology in Ruminants; Karger, 1997, Vol. 2, .
Linkhart, T.A.; Keffer, M.J. Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II release from cultured neonatal mouse calvaria by parathyroid hormone, transforming growth factor-beta, and 1, 25-dihydroxyvitamin D3. Endocrinology, 1991, 128, 1511-1158.
Phillips, L.S.; Goldstein, S.; Pao, C.I. Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes. Diabetes, 1991, 40, 1525-1554.
Harp, J.B.; Goldstein, S.; Phillips, L.S. Nutrition and somatomedin. XXIII. Molecular regulation of IGF-I by amino acid availability in cultured hepatocytes. Diabetes, 1991, 40, 95-101.
López-Oliva, M.E.; Agis-Torres, A.; Muñoz-Martínez, E. The modulator effect of GH on skeletal muscle lysosomal enzymes is dietary protein dependent. Growth Horm. IGF Res., 2007, 17, 137-148.
Harel, Z.; Tannenbaum, G.S. Dietary protein restriction impairs both spontaneous and growth hormone-releasing factor-stimulated growth hormone release in the rat. Endocrinology, 1993, 133, 1035-1077.
Smith, S.R.; Edgar, P.J.; Pozefsky, T.; Chhetri, M.K.; Prout, T.E. Growth hormone in adults with protein-calorie malnutrition. J. Clin. Endocrinol. Metab., 1974, 39, 53-62.
Isidori, A.; Lo, M.A.; Cappa, M. A study of growth hormone release in man after oral administration of amino acids. Curr. Med. Res. Opin., 1981, 7, 475-555.
Probsthensch, N.M.; Wang, H.; Goh, V.H.; Seow, A.; Lee, H.P.; Yu, M.C. Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women. Cancer Epidemiol. Biomarkers Prev., 2003, 12, 739-746.
Maskarinec, G.; Takata, Y.; Kaaks, R. The relation between nutritional factors and insulin–like growth factor-I in premenopausal women of different ethnicity. Eur. J. Nutr., 2005, 44, 105-113.
Joslowski, G.; Remer, T.; Assmann, K.E.; Krupp, D.; Cheng, G.; Garnett, S.P.; Kroke, A.; Wudy, S.A.; Günther, A.L.; Buyken, A.E. Animal protein intakes during early life and adolescence differ in their relation to the growth hormone-insulin-like-growth-factor axis in young adulthood. J. Nutr., 2013, 143, 147-200.
Choi, Y.H.; Kim, K.W.; Han, H.S.; Nam, T.J.; Lee, B.J. Dietary Hizikia fusiformis glycoprotein-induced IGF-1 and IGFBP-3 associated to somatic growth, polyunsaturated fatty acid metabolism, and immunity in juvenile olive flounder Paralichthys olivaceus. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol., 2014, 167, 1-6.
Tran, C.D.; Diorio, C.; Bérubé, S.; Pollak, M.; Brisson, J. Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants. Am. J. Clin. Nutr., 2006, 84, 1518-1526.
Harrison, S.; Lennon, R.; Holly, J.; Higgins, J.P.T.; Gardner, M.; Perks, C.; Gaunt, T.; Tan, V.; Borwick, C.; Emmet, P. Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis. Cancer Causes Control, 2017, 28, 497-528.
Crowe, F.L.; Key, T.J.; Allen, N.E.; Appleby, P.N.; Roddam, A.; Overvad, K.; Gronbaek, H.; Tjonneland, A.; Halkjaer, J.; Dossus, L. The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 1333-1372.
Du, X.; Shi, Z.; Peng, Z.; Zhao, C.; Zhang, Y.; Wang, Z.; Li, X.; Liu, G.; Li, X. Acetoacetate induces hepatocytes apoptosis by the ROS-mediated MAPKs pathway in ketotic cows. J. Cell. Physiol., 2017, 232, 3296-3308.
Arvidson, K.; Abdallah, B.M.; Applegate, L.A.; Baldini, N.; Cenni, E.; Gomez-Barrena, E.; Granchi, D.; Kassem, M.; Konttinen, Y.T.; Mustafa, K. Bone regeneration and stem cells. J. Cell. Mol. Med., 2011, 15, 718-746.
Kimura, T.; Kuwata, T.; Ashimine, S.; Yamazaki, M.; Yamauchi, C.; Nagai, K.; Ikehara, A.; Feng, Y.; Dimitrov, D.S.; Saito, S. Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment. Clin. Cancer Res., 2010, 16, 121-129.
Tsiridis, E.; Upadhyay, N.; Giannoudis, P. Molecular aspects of fracture healing: Which are the important molecules? Injury, 2007, 38, S11-S25.
Elias, W.Y. Assessment of the osteogenic potential of morphogenetic protein-2 and insulin-like growth factor-I on adipose tissue-derived stem cells. J. Biomed. Sci., 2016, 5, 1-6.
Rico‐Llanos, G.A.; Becerra, J.; Visser, R. Insulin‐like growth factor‐1 (IGF‐1) enhances the osteogenic activity of bone morphogenetic protein‐6 (BMP‐6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF‐1 is combined with BMP‐2. J. Biomed. Mater. Res. A, 2017, 105, 1867-1875.
Czech, M.P.; Corvera, S. Signaling mechanisms that regulate glucose transport. J. Biol. Chem., 1999, 274, 1865-1872.
Shepherd, P.R.; Withers, D.J.; Siddle, K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem. J., 1998, 333, 471-560.
Kawamura, N.; Kugimiya, F.; Oshima, Y.; Ohba, S.; Ikeda, T.; Saito, T.; Shinoda, Y.; Kawasaki, Y.; Ogata, N.; Hoshi, K. Akt1 in osteoblasts and osteoclasts controls bone remodeling. PLoS One, 2007, 2, e1058.
Rached, M.T.; Kode, A.; Xu, L.; Yoshikawa, Y.; Paik, J.H.; Depinho, R.A.; Kousteni, S. FoxO1 is a positive regulator of bone formation by favoring protein synthesis and resistance to oxidative stress in osteoblasts. Cell Metab., 2010, 11, 147-160.
Marsell, R.; Sisask, G.; Nilsson, Y.; Sundgren-Andersson, A.K.; Andersson, U.; Larsson, S.; Nilsson, O.; Ljunggren, Ö.; Jonsson, K.B. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone, 2012, 50, 619-627.
Shin, I.; Yakes, F.M.; Rojo, F.; Shin, N.Y.; Bakin, A.V.; Baselga, J.; Arteaga, C.L. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat. Med., 2002, 8, 1145-1152.
Brunet, A.; Bonni, A.; Zigmond, M.J.; Lin, M.Z.; Juo, P.; Hu, L.S.; Anderson, M.J.; Arden, K.C.; Blenis, J.; Greenberg, M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 1999, 96, 857-924.
Walsh, K.; Shiojima, I.; Abel, E.D. Insulin signaling in the heart. J. Mol. Cell. Cardiol., 2001, 33, A149-A149.
Yang, J.; Zhang, X.; Wang, W.; Liu, J. Insulin stimulates osteoblast proliferation and differentiation through ERK and PI3K in MG-63 cells. Cell Biochem. Funct., 2010, 28, 334-341.
Xiao, G.; Jiang, D.; Thomas, P.; Benson, M.D.; Guan, K.; Karsenty, G.; Franceschi, R.T. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J. Biol. Chem., 2000, 275, 4453-4461.
Ge, C.; Xiao, G.; Jiang, D.; Franceschi, R.T. Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J. Cell Biol., 2007, 176, 709-726.
Schindeler, A.; Little, D.G. Ras-MAPK signaling in osteogenic differentiation: Friend or foe? J. Bone Miner. Res., 2006, 21, 1331-1338.
Takeuchi, Y.; Suzawa, M.; Kikuchi, T.; Nishida, E.; Fujita, T.; Matsumoto, T. Differentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cells. J. Biol. Chem., 1997, 272, 29309-29324.
Xiao, G.; Wang, D.; Benson, M.D.; Karsenty, G.; Franceschi, R.T. Role of the alpha2-integrin in osteoblast-specific gene expression and activation of the Osf2 transcription factor. J. Biol. Chem., 1998, 273, 32988-33081.
Konosuke Nakayama, M.D.; Tamura, Y.; Suzawa, M.; Harada, S.I.; Fukumoto, S.; Kato, M.; Miyazono, K.; Rodan, G.A.; Takeuchi, Y.; Fujita, T. Receptor tyrosine kinases inhibit bone morphogenetic protein-smad responsive promoter activity and differentiation of murine MC3T3-E1 osteoblast-like cells. J. Bone Miner. Res., 2003, 18, 827-861.
Higuchi, C.; Myoui, A.; Hashimoto, N.; Kuriyama, K.; Yoshioka, K.; Yoshikawa, H. Itoh, K. Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of the extracellular matrix. J. Bone Miner. Res., 2002, 17, 1785-1878.
Burguera, B.; Brunetto, A.; Garcia-Ocana, A.; Teijeiro, R.; Esplen, J.; Thomas, T.; Couce, M.E.; Zhao, A. Leptin increases proliferation of human steosarcoma cells through activation of PI(3)-K and MAPK pathways. Med. Sci. Monit., 2006, 12, 341-349.
Blume-Jensen, P.; Hunter, T. Oncogenic kinase signaling. Nature, 2001, 411, 355-419.
Grey, A.; Chen, Q.; Xu, X.; Callon, K.; Cornish, J. Parallel phosphatidylinositol-3 kinase and p42/44 mitogen-activated protein kinase signaling pathways subserve the mitogenic and antiapoptotic actions of insulin-like growth factor I in osteoblastic cells. Endocrinology, 2003, 144, 4886-4978.
Freudenheim, J.L.; Johnson, N.E.; Smith, E.L. Relationships between usual nutrient intake and bone-mineral content of women 35-65 years of age: longitudinal and cross-sectional analysis. Am. J. Clin. Nutr., 1986, 44, 863-938.
Metz, J.A.; Anderson, J.J.; Gallagher, P.N. Jr. Intakes of calcium, phosphorus, and protein, and physical-activity level are related to radial bone mass in young adult women. Am. J. Clin. Nutr., 1993, 58, 537-542.
Tang, M.; Leidy, H.J.; Campbell, W.W. Regional, but not total, body composition changes in overweight and obese adults consuming a higher protein, energy-restricted diet are sex specific. Nutr. Res., 2013, 33, 629-635.
Langsetmo, L.; Barr, S.I.; Berger, C.; Kreiger, N.; Rahme, E.; Adachi, J.D.; Papaioannou, A.; Kaiser, S.M.; Prior, J.C.; Hanley, D.A. Associations of protein intake and protein source with bone mineral density and fracture risk: A population-based cohort study. J. Nutr. Health Aging, 2015, 19, 861-868.
Heaney, R.P. Protein intake and bone health: The influence of belief systems on the conduct of nutritional science. Am. J. Clin. Nutr., 2001, 73, 5-6.
Sellmeyer, D.E.; Stone, K.L.; Sebastian, A.; Cummings, S.R. A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. Am. J. Clin. Nutr., 2001, 73, 118-139.
Hannan, M.T.; Tucker, K.L.; Dawson-Hughes, B.; Cupples, L.A.; Felson, D.T.; Kiel, D.P. Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study. J. Bone Miner. Res., 2000, 15, 2504-2515.
Dawson-Hughes, B.; Harris, S. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am. J. Clin. Nutr., 2002, 75, 773-781.
Langsetmo, L.; Shikany, J.M.; Cawthon, P.M.; Cauley, J.A.; Taylor, B.C.; Vo, T.N.; Bauer, D.C.; Orwoll, E.S.; Schousboe, J.T.; Ensrud, K.E. The association between protein intake by source and osteoporotic fracture in older men: A prospective cohort study. J. Bone Miner. Res., 2017, 32, 592-600.
Yoneme, H.; Hatakeyama, J.; Danjo, A.; Oida, H.; Yoshinari, M.; Aijima, R.; Murata, N.; Watanabe, T.; Oki, Y.; Kido, M.A. Milk basic protein supplementation enhances fracture healing in mice. Nutrition, 2015, 31, 399-405.
Beasley, J.M.; Lacroix, A.Z.; Larson, J.C.; Huang, Y.; Neuhouser, M.L.; Tinker, L.F.; Jackson, R.; Snetselaar, L.; Johnson, K.C.; Eaton, C.B. Biomarker-calibrated protein intake and bone health in the Women’s Health Initiative clinical trials and observational study. Am. J. Clin. Nutr., 2014, 99, 934-973.
Friedman, S.M.; Mendelson, D.A. Epidemiology of fragility fractures. Clin. Geriatr. Med., 2014, 30, 175-181.
Roughead, Z.K.; Johnson Lklykken, G.I.; Hunt, J.R. Controlled high meat diets do not affect calcium retention or indices of bone status in healthy postmenopausal women. J. Nutr., 2003, 133, 1020-1025.
Kerstetter, J.E.; O’brien, K.O.; Insogna, K.L. Dietary protein affects intestinal calcium absorption. Am. J. Clin. Nutr., 1998, 68, 859-923.
Howard, J.E. Calcium metabolism, bones and calcium homeostasis; A review of certain current concepts. J. Clin. Endocrinol. Metab., 1957, 17, 1105-1123.
Elefteriou, F.; Benson, M.D.; Sowa, H.; Starbuck, M.; Liu, X.; Ron, D.; Parada, L.F.; Karsenty, G. ATF4 mediation of NF1 functions in osteoblst reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab., 2006, 4, 441-491.
Macdonell, R.; Hamrick, M.W.; Isales, C.M. Protein/amino-acid modulation of bone cell function. Bonekey Rep., 2016, 5, 827-833.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [115 - 124]
Pages: 10
DOI: 10.2174/1389203719666180514143828
Price: $65

Article Metrics

PDF: 18