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Nutritional Zinc Plays a Pivotal Role in Bone Health and Osteoporosis Prevention

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Nutritional Zinc Plays a Pivotal Role in Bone Health and Osteoporosis Prevention Edorium J Nutr Diet 2015;1:1–8. Yamaguchi 1 www.edoriumjournals.com/ej/nd EDITORIAL OPEN ACCESS Nutritional zinc plays a pivotal role in bone health and osteoporosis prevention Masayoshi Yamaguchi Bone homeostasis is maintained through a delicate cardiovascular diseases, cancer and diabetesaffecting the balance between osteoblastic bone formation and aging population [6–8]. osteoclastic bone resorption [1, 2]. Bone mass is reduced Osteoporosis has also been shown to induce after by decrease in osteoblastic bone formation and increase diabetes (type I and II), obesity, inflammatory disease, and in osteoclastic bone resorption. Numerous pathological various pathophysiological states. Diabetic osteoporosis processes have the capacity to disrupt this equilibrium is noticed in recent years [7, 8]. Diabetes is frequent leading to conditions where the rate of bone resorption in the elderly, and therefore frequently coexists with outpaces the rate of bone formation. Osteoporosis is osteoporosis. Furthermore, there has also been a global induced with decrease in bone mass. The most dramatic increase in the prevalence of obesity, with obesity-related expression of osteoporosis is represented by fractures of diabetes currently affecting over 366 million adults the proximal femur for which the number increases as worldwide and projections that this will reach 552 million the population ages [3, 4]. Osteoporosis is characterized by 2030 [9]. Type 1 diabetes, and more recently type 2 by reduced bone strength and an increased risk for low- diabetes, has been associated with increased fracture risk. trauma fractures. Bone mass is dramatically reduced In Western societies, mean body weight has dramatically after menopause, which depresses the secretion of increased in older people, and a similar trend exists in ovarian hormone (estrogen) in women [5]. Deficiency Asia. Yet insufficient attention has been directed to the of estrogen advances osteoclastic bone resorption. problem of osteoporotic fractures in the over weight and This is very important as a primary osteoporosis. obese. Osteoporotic fractures occur in overweight or obese Postmenopausal osteoporosis, a consequence of ovarian people, and obese men may be particularly susceptible hormone deficiency, is the archetypal osteoporotic [10, 11]. The National Health and Nutrition Examination condition in women after menopause and leads to bone Survey have reported that 63% of osteoporotic patients destruction through complex and diverse metabolic and have hyperlipidemia. Epidemiological studies reveal an biochemical changes.About 40% of women in developed inverse relationship between serum cholesterol levels countries will experience an osteoporosis-related fracture and bone mineral content and density, independent of in the course of their lifetime, with men experiencing age and body mass index. Diet-induced hyperlipidemia is approximately one-third to one-half the risk of women. also associated with a reduction in bone mineral content According to a recent World Health Organization report, and density in animals [9, 10]. Hyperlipidemia induces osteoporosis has become a global health problem with secondary hyperparathyroidism and impairs bone a disease incidence and mortality rate similar to that of regeneration and mechanical strength. Bone mass is reduced due to decreased osteoblastic bone formation and increased osteoclastic bone Masayoshi Yamaguchi resorption. Malnutrition or undernutrition is often Affiliations: Department of Hematology and Medical Oncol- observed in the elderly, and it appears to be more intense ogy, Emory University School of Medicine, Atlanta, USA in patients with bone fracture than in the general aging Corresponding Author: Masayoshi Yamaguchi, PhD, De- population [12]. Deficiency in both micronutrients and partment of Hematology and Medical Oncology, Emory macronutrients appears to be strongly implicated in the University School of Medicine, 1365 C Clifton Road NE, pathogenesis and the consequences of bone fracture in Atlanta, GA 30322, USA; E-mail: yamamasa1155@ya- the osteoporotic elderly. Nutritional and functional food hoo.co.jp factors may have potential effects to delay degenerative bone disorders such as osteoporosis. There is growing Received: 22 September 2014 evidence that nutritional and functional food factors Published: 06 January 2015 regulate bone homeostasis and have restorative effects on bone loss with various pathophysiologic conditions Edorium Journal of Nutrition and Dietetics, Vol. 1; 2015. Edorium J Nutr Diet 2015;1:1–8. Yamaguchi 2 www.edoriumjournals.com/ej/nd [13, 14]. Zinc, genistein and vitamin K2 (menaquinone-7) cell differentiation, cell proliferation, and mineralization have been shown to have osteogenic effects and these in osteoblasts, thereby promoting bone formation. factors play a role in the prevention of bone loss in animal Zinc has been shown to reveal a suppressive effect on model for osteoporosis and human subjects [13, 14]. osteoclastic bone resorption in vitro [37]. Calvaria, which Interestingly, their combination with zinc has been found were removed from weanling rats, were cultured for to reveal potential synergistic effects on osteogenesis [13- periods of up to 48 hours in a medium containing various 15]. Supplemental intake of these ingredients may be a bone-resorbing factors [PTH, prostaglandin E2 (PGE2), useful tool in bone health and osteoporosis prevention. interleukin-1α (IL-1α), and lipopolysaccharide (LPS)]. Zinc plays a pivotal role in the regulation of bone Decrease in bone calcium content caused by these factors homeostasis. Many zinc-related proteins are found was suppressed in the presence of zinc. Osteoclasts, to involve in the regulation of cellular function in bone-resorbing cells, are formed by differentiation of osteoblasts and osteoclasts. These factors play an bone marrow cells. Zinc revealed suppressive effects on essential role in bone homeostasis, and those are osteoclast-like cell formation enhanced by various bone- known as zinc finger transcription factors (Osterix, resorbing factors in mouse marrow culture in vitro [37, Runx2/Cbfa1 and Cas-interacting zinc finger protein), 38]. Suppressive effects of zinc on osteoclast-like cell zinc transporter, Schnurri-3, an essential regulator of formation in mouse bone marrow culture were equal in adult bone formation, and TRAF6-inhibitory zinc finger comparison with the effect of other anti-bone resorbing protein, a tumor necrosis factor receptor-associated agents (calcitonin, 17β-estradiol, or acetazolamide) factor 6 [16–22]. Nutritional conditions of zinc may [33]. In addition, zinc caused apoptotic cell death of influence function of osteoblastes and osteoclasts that mature osteoclast-like cells isolated from rat femoral are related to zinc finger proteins. Zinc is required for the tissues [39]. Thus, zinc was found to reveal suppressive growth, development and maintenance of healthy bones. effects on osteoclastogenesis and osteoclastic cell death. Retardation of bone growth is a common finding in various The receptor activator of nuclear factor-kappaB ligand conditions associated with zinc deficiency [23]. Skeleton (RANKL) plays a pivotal role in the differentiation from contains a large proportion of the total body burden of preosteoclasts to mature osteoclasts [2]. RANKL is zinc. Bone zinc has been shown to concentrate in the expressed in osteoblastic cells and bone marrow stromal layer of osteoid prior to calcification [24]. Zinc deficiency cells in response to osteotropic factors. RANKL/RANK is associated with many kinds of skeletal abnormalities pathway is essential for osteoclast differentiation [2]. in fetal and postnatal development. Nutritional zinc The effect of RANKL is abrogated by osteoprotegerin plays a physiologically important role in bone growth. (OPG), a natural antagonist of RANKL that is produced Osteoporotic patients have been shown to have lower in osteoblastic cells [2]. TNF receptor-associated factor levels of skeletal zinc than control. In postmenopausal (TRAF) family proteins are adaptor molecules. TRAFs women, urinary zinc has been suggested as a marker of bind to the membrane-proximal region of RANK and bone resorption, since women with osteoporosis excrete IL-1R-associated kinase and are critically involved in over than 800 μg zinc per g creatinine in urine [25]. the intracellular signal transduction including NF-κB Zinc stimulates osteoblastic bone formation and and mitogen-activated protein kinase (MAPK) activation osteoclastic bone resorption in vitro and in vivo [26, 27]. [2]. Zinc was found to reveal suppressive effects on Bone calcium content, alkaline phosphatase activity and RANKL-induced osteoclast-like cell formation in mouse collagen content have were increased after culture with marrow culture [40]. Also, zinc inhibited TNF-α-induced zinc, and these increases were depressed in the presence osteoclastogenesis [40]. Suppressive effects of zinc on of an inhibitor of protein synthesis. Endogenous zinc in osteoclastogenesis may be involved in inhibitory effect on the bone tissues was shown to reveal direct stimulatory RANKL stimulation. Culture with zinc has been shown effects on bone formation and mineralization due to to have stimulatory effects on the expression of OPG stimulating protein synthesis [28-30]. Zinc was shown to mRNA in osteoblastic cells. The mechanism by which stimulate differentiation and proliferation in osteoblastic zinc suppresses osteoclastogenesis may also be related to MC3T3-E1 cells
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