Category Archives: Zinc

Zinc Deficiency or Calorie Restriction Impares Bone Development in Weanling Rats

Abstract

Zinc-deficient rats have more limited bone recovery during repletion than diet-restricted rats.

The objective of this study was to investigate the effects of dietary zinc deficiency and diet restriction on bone development in growing rats, and to determine whether any adverse effects could be reversed by dietary repletion. Weanling rats were fed either a zinc-deficient diet ad libitum (ZD; <1 mg zinc/kg) or nutritionally complete diet (30 mg zinc/kg) either ad libitum (CTL) or pair-fed to the intake of the ZD group (DR; diet-restricted) for 3 weeks (deficiency phase) and then all groups were fed the zinc-adequate diet ad libitum for 3, 7, or 23 days (repletion phase). Excised femurs were analyzed for bone mineral density (BMD) using dual-energy x-ray absorptiometry, and plasma was analyzed for markers of bone formation (osteocalcin) and resorption (Ratlaps). After the deficiency phase, ZD had lower body weight and reduced femur BMD, zinc, and phosphorus concentrations compared with DR; and these parameters were lower in DR compared with CTL. Femur calcium concentrations were unchanged among the groups. Reduced plasma osteocalcin in ZD and elevated plasma Ratlaps in DR suggested that zinc deficiency limits bone formation while diet restriction accelerates bone resorption activity. After 23 days of repletion, femur size, BMD, and zinc concentrations remained lower in ZD compared with DR and CTL. Body weight and femur phosphorus concentrations remained lower in both ZD and DR compared with CTL after repletion. There were no differences in plasma osteocalcin concentrations after the repletion phase, but the plasma Ratlaps concentrations remained elevated in DR compared with CTL. In summary, both ZD and DR lead to osteopenia during rapid growth, but the mechanisms appear to be due to reduced modeling in ZD and higher turnover in DR. Zinc deficiency was associated with a greater impairment in bone development than diet restriction, and both deficiencies limited bone recovery during repletion in growing rats.

Hosea HJ, Taylor CG, Wood T, Mollard R…
Exp. Biol. Med. (Maywood) Apr 2004
PMID: 15044713

Zinc, but not Zinc-Carnosine, Enhances Anabolic Effect of IGF-1 in Mouse Osteoblasts In Vitro

Abstract

Zinc modulation of insulin-like growth factor’s effect in osteoblastic MC3T3-E1 cells.

Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation, was investigated in vitro. After subculture for 3 days, the cells were cultured for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of protein concentration, deoxyribonucleic acid (DNA) content, and cell number in the cells. These increases were markedly enhanced by the presence of zinc sulfate (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-5) M). Also, the cellular alkaline phosphatase activity was synergistically increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase activity and protein concentration in the cells was clearly prevented by the presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid (10(-7) M) with an effective concentration. However, staurosporin had a partial inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I plus zinc effect. The present study demonstrates that the anabolic effect of IGF-I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be mediated through the signaling pathway of protein kinase C and protein phosphatase in the cells.

Matsui T, Yamaguchi M
Peptides 1995
PMID: 8532589

Too Much Zinc Reduces Bone Density in Rats

Abstract

Marginal zinc deficiency exacerbates bone lead accumulation and high dietary zinc attenuates lead accumulation at the expense of bone density in growing rats.

Environmental lead exposure is associated with reduced bone growth and quality, which may predispose to osteoporosis. Zinc supplementation may reduce lead accumulation; however, effects on bone development have not been addressed. Our objective was to investigate the effects of marginal zinc (MZ) and supplemental zinc (SZ) intakes on bone lead deposition and skeletal development in lead-exposed rats. In a factorial design, weanling Sprague-Dawley rats were assigned to MZ (8 mg/kg diet); zinc-adequate control (CT; 30 mg/kg); zinc-adequate, diet-restricted (DR; 30 mg/kg); or SZ (300 mg/kg) groups, with and without lead acetate-containing drinking water (200 mg Pb/l) for 3 weeks. Excised femurs were analyzed for bone mineral density (BMD) by dual-energy x-ray absorptiometry, morphometry, and mineral content. MZ had higher femur lead and lower femur zinc concentrations and impaired skeletal growth and mineralization than CT. DR inhibited growth but did not result in higher femur lead concentrations than CT. SZ had higher femur zinc and lower femur lead concentrations than the other treatments. DR and SZ had impaired BMD versus CT and MZ. Lead also retarded skeletal growth and impaired BMD, but an interaction between lead and MZ was only found for femoral knee width, which was lower in MZ exposed to lead. In summary, while MZ deficiency exacerbated bone lead concentration, it generally did not intensify lead toxicity. SZ was protective against bone lead but was detrimental to BMD, suggesting that the optimal level of SZ to reduce lead absorption, while supporting growth and bone development, requires further investigation.

Jamieson JA, Taylor CG, Weiler HA
Toxicol. Sci. Jul 2006
PMID: 16624848 | Free Full Text

Zinc Protects Bone Against Cadmium in Rats

Abstract

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats.

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60mg/l) or/and Cd (5 and 50mg/l) for 6months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.

Brzóska MM, Rogalska J
Toxicol. Appl. Pharmacol. Oct 2013
PMID: 23726800

Zinc Deficiency Reduces Bone Density in Rats

Abstract

Zinc deficiency reduces bone mineral density in the spine of young adult rats: a pilot study.

The objective of this study was to investigate the effects of zinc deficiency initiated during adolescence on skeletal densitometry, serum markers of bone metabolism, femur minerals and morphometry in young adult rats. Ten-week-old male rats were fed a <1-mg Zn/kg diet (9ZD), a 5-mg Zn/kg diet (9MZD) or a 30-mg Zn/kg diet (9CTL) for up to 9 weeks. Analyses included bone mineral density, serum osteocalcin and C-terminal peptides of type I collagen, serum zinc, femur zinc, calcium and phosphorus, and femur morphometry. Bone mineral density was 14% lower in the spine of 9ZD, but was not altered in the whole body, tibia or femur, or in any of the aforementioned sites in 9MZD, compared to 9CTL. When adjusted for size, spine bone mineral apparent density was still 8% lower in 9ZD than 9CTL. Serum osteocalcin, a marker for bone formation, was approximately 33% lower in 9ZD compared to both 9MZD and 9CTL. The 9ZD and 9MZD had 57% lower femur zinc and 56-88% lower serum zinc concentrations compared to 9CTL. These findings indicate that severe zinc deficiency initiated during adolescence may have important implications for future bone health, especially with regards to bone consolidation in the spine.

Ryz NR, Weiler HA, Taylor CG
Ann. Nutr. Metab. 2009
PMID: 19506366

Zinc-Carnosine > Zinc at Enhancing Estrogen’s Anabolic Effect on Osteoblasts In Vitro

Abstract

Zinc enhancement of 17beta-estradiol’s anabolic effect in osteoblastic MC3T3-E1 cells.

The anabolic effect of 17beta-estradiol in osteoblastic MC3T3-E1 cells was investigated. The cells were cultured for 3 days in the medium containing either vehicle or 17beta-estradiol (10(-11)-10(-9) M). 17beta-Estradiol significantly increased alkaline phosphatase activity and protein concentration in the cells. The steroid (10(-9) M) also significantly elevated the cell numbers and the cellular DNA content. The anabolic effect by 17beta-estradiol was blocked by the presence of dipicolinate (10(-3) M), a chelator of zinc ion, suggesting a role of cellular zinc in osteoblastic cell function. The presence of zinc sulfate (10(-5) M) or beta-alanyl-L-histidinato zinc (AHZ) (10(-5) M) significantly enhanced the 17beta-estradiol (10(-10) or 10(-9) M)-induced increase of alkaline phosphatase activity and protein concentration in the cells; the effect of AHZ was greater than that of zinc sulfate. The enhancement by zinc compounds was not based on the augmentation of osteoblastic cell numbers. The co-addition of cycloheximide (10(-6) M), an inhibitor of protein synthesis, completely blocked the zinc compound (10(-5) M)-induced enhancement of 17beta-estradiol’s (10(-9) M) effect to increase alkaline phosphatase activity and protein concentration in the cells. Moreover, the anabolic effect of 17beta-estradiol together with or without zinc compounds was abolished by the presence of staurosporine (10(-8) M), an inhibitor of protein kinase C, or of okadaic acid (10(-7) M), an inhibitor of protein phosphatase. The present study demonstrates that the anabolic effect of 17beta-estradiol is enhanced by zinc-chelating dipeptide in osteoblastic MC3T3-E1 cells, and that the enhancing effect may involve protein synthesis and protein kinase activity.

Yamaguchi M, Matsui T
Calcif. Tissue Int. Jun 1997
PMID: 9164827

Zinc Induces Bone Formation in Rat Cells

Abstract

Zinc stimulation of bone protein synthesis in tissue culture. Activation of aminoacyl-tRNA synthetase.

The present investigation was undertaken to clarify the effect of zinc on bone protein synthesis in tissue culture. Calvaria were removed from 3-week-old male rats and cultured for periods up to 96 hr in Dulbecco’s Modified Eagle Medium (high glucose, 4500 mg/dl) supplemented with antibiotics and bovine serum albumin. The calvaria were incubated at 37 degrees in 5% CO2/95% air in the medium containing 10(-6)-10(-4) M zinc. Zinc content in bone cells was increased when the culture was treated with 10(-5) and 10(-4) M zinc for 48 hr. When calvaria cultured in the presence of 10(-4) M zinc were pulsed with [14C]uridine, the incorporation of [14C]uridine into the bone RNA was not increased significantly. In the pulse with [3H]leucine, the presence of 10(-5) to 10(-4) M zinc in the medium caused a significant increase in the incorporation of [3H]leucine into the acid-insoluble residues of bone tissue. This increase was blocked completely by treatment with 10(-7) M cycloheximide, an inhibitor of protein synthesis. When [3H]leucine was added into the reaction mixture containing the 5500 g supernatant fraction of the homogenate prepared from calvaria cultured in the presence of 10(-4) M zinc, the in vitro protein synthesis was increased about 2-fold. The activity of [3H]leucyl-tRNA synthetase in the 105,000 g supernatant fraction (cytosol) of the bone homogenate was increased about 2-fold by the culture with 10(-4) M zinc. The presence of 10(-4) M dipicolinate, a specific chelator of zinc, in the culture medium negated the effect of zinc on [3H]leucyl-tRNA synthetase activity. The addition of 10(-7) to 10(-6) M zinc into the reaction mixture containing enzyme extracts obtained from uncultured rat calvaria caused a 2-fold increase of [3H]leucyl-tRNA synthetase activity. These results clearly indicate that zinc induces the stimulation of protein synthesis at the translational level in bone cells. The present study further supports the view that zinc increases protein synthesis in bone cells and that the metal induces bone formation.

Yamaguchi M, Oishi H, Suketa Y
Biochem. Pharmacol. Nov 1988
PMID: 2461201

Copper + Manganese + Zinc Necessary for Optimal Bone Development and Density

Abstract

The role of trace minerals in osteoporosis.

Osteoporosis is a multifactorial disease with dimensions of genetics, endocrine function, exercise and nutritional considerations. Of particular considerations are calcium (Ca) status, Vitamin D, fluoride, magnesium and other trace elements. Several trace elements, particularly copper (Cu), manganese (Mn) and zinc (Zn), are essential in bone metabolism as cofactors for specific enzymes. Our investigations regarding the role of Cu, Mn and Zn in bone metabolism include data from studies with animals on Cu- and Mn-deficient diets. We have also demonstrated cellular deficiencies using bone powder implants, as well as fundamental changes in organic matrix constituents. In clinical studies we have demonstrated the efficacy of Ca, Cu, Mn and Zn supplementation on spinal bone mineral density in postmenopausal women. Each of these studies demonstrated the necessity of trace elements for optimal bone matrix development and bone density sustenance.

Saltman PD, Strause LG
J Am Coll Nutr Aug 1993
PMID: 8409100