Abstract

FELICE, J.I et al. In vivo effects of Metformin on the alterations of bone micro-architecture associated with fructose-induced Metabolic Syndrome in rats. Rev. argent. endocrinol. metab. [online]. 2011, vol.48, n.4, pp.193-199. ISSN 1851-3034.

Several clinical studies have demonstrated that the Metabolic Syndrome (MS) is associated with a decrease in bone mineral density, and with an increased risk for non-vertebral osteoporotic fractures. We have recently found that orally administered Metformin induces osteogenic effects in rats, promoting osteoblastic differentiation of bone marrow progenitor cells and increasing the repair of bone lesions. In the present work we have evaluated the effects of Fructose-induced MS on bone micro-architecture in rats, and the possible modulation of these effects by orally administered Metformin. We utilized young male Sprague-Dawley rats, divided into four groups: C (non-treated controls); C+M (100 mg/kg/day of Metformin in drinking water); F (10 % of Fructose in drinking water); and F+M (Fructose+Metformin in drinking water). After three weeks of all treatments blood samples were taken, after which animals were sacrificed by cervical dislocation under anaesthesia. Femurs were then dissected for evaluation of metaphyseal micro-architecture after Haematoxilin-Eosin staining of 5 μm histological slices of decalcified bone. In particular, osteocytic density and relative trabecular volume were determined. An increase in serum glucose and triglycerides was observed in Fructose-treated rats, in accordance with the development of MS. In rats treated with Metformin alone (group C+M), the analysis of femoral metaphyses showed an increase in trabecular osteocytic density (118 % of control [group C], p<0.05). Treatment with Fructose alone (group F) significantly decreased ostecytic density (79 % of control, p<0.05), while co-treatment with Fructose and Metformin partially reverted this decrease (group F+M, 88 % of control). Similarly, the relative trabecular volume of femoral metaphysic was increased by treatment with Metformin alone (129% of control), was reduced in Fructose-treated rats (89 % of control), and tended to revert back to control values after Fructose-Metformin co-treatment (94 % of control). These results show for the first time that (a) Fructose-induced MS in rats alters their femoral metaphysis micro-architecture; and that (b) these deleterious effects can be partially prevented by orally administered Metformin.

Keywords : Metabolic syndrome; Bone micro-architecture; Metformin.

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