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Zinc supplementation reduces RANKL/OPG ratio and prevents bone architecture alterations in ovariectomized and type 1 diabetic rats

Ferreira, Elaine C.S., Bortolin, Raul H., Freire-Neto, Francisco P., Souza, Karla S.C., Bezerra, João F., Ururahy, Marcela A.G., Ramos, Ana M.O., Himelfarb, Silvia T., Abreu, Bento J., Didone, Thiago V.N., Pedrosa, Lucia F.C., Medeiros, Aldo C., Doi, Sonia Q., Brandão-Neto, José, Hirata, Rosário D.C., Rezende, Luciana A., Almeida, Maria G., Hirata, Mario H., Rezende, Adriana A.
Nutrition research 2017 v.40 pp. 48-56
alkaline phosphatase, animal disease models, blood serum, bone resorption, calcium, diabetes, dietary mineral supplements, enzyme activity, estrogens, females, laboratory animals, ovariectomy, phosphorus, protective effect, rats, zinc
Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.