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BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB).MethodsWe recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h.ResultsThe hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group.ConclusionsOur data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

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type, including the morphologic appearance and biosynthetic activity, is diff erent. OB diff erentiation includes three distinct periods: 1) Growth (proliferation) and extracellular matrix (ECM) biosynthesis, 2) ECM development and maturation, and 3) ECM mineralization. During the period of active proliferation, many genes are expressed, such as cell cycle genes (c-fos, c-myc, histone) and those of extracellular matrix proteins (procollagen I, fi bronectin). This is followed by a stage of matrix maturation characterized by a high expression of bone alkaline phosphatase. When mineralization begins, genes for proteins such as osteocalcin, bone sialoprotein and osteopontin are expressed [8, 9]. The eff ects of 1,25dihydroxyvitamin D3 on OB have been well characterized in rats and human osteoblast cultures; in both cases, stimulation and inhibition have been described in genes related to the diff erentiation of osteoblastic phenotypes [10, 11]. It is well established that estrogens infl uence osteoblastic growth and diff erentiation [12, 13]. Nevertheless, the simultaneous action of both stimuli has not been described.