Ramón Pérez-Cano

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide and it is associated with an increased risk of osteoporosis and fragility fractures. Our aim is to analyze the effect of T2DM on bone quality. This is a case-control study. The studied population consisted of 140 patients: 54 subjects with hip fracture (OP) without T2DM, 36 patients with hip fracture and T2DM (OP-T2DM), 28 patients with osteoarthritis (OA) without T2DM, and 22 patients with OA and T2DM (OA-T2DM). Bone markers, bone mineral density, FRAX score, microstructural, and bone material strength from femoral heads were assessed. The group with hip fracture presented lower BMD values than OA (p < 0.05). The OP, OP-T2DM, and OA-T2DM groups showed a decrease in bone volume fraction (BV/TV), in trabecular number (Tb.N), and in trabecular thickness (Tb.Th), while an increase was presented in the structural model index (SMI) and trabecular bone pattern factor (Tb.Pf), The groups OP, OP-T2DM, and OA-T2DM also presented lower values than those in group OA regarding the biomechanical parameters in the form of Young’s modulus or elastic modulus, toughness, ultimate stress, ultimate load, extrinsic stiffness, and work to failure (p < 0.05). Our results show the negative effect of type 2 diabetes mellitus on trabecular bone structure and mechanical properties.

Type 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). We 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. The 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. Our 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.

Experimental studies suggested that both, oxidative stress and the Wnt pathway, are important factors in the regulation of bone remodeling. Thus, low antioxidant levels and elevated markers of Wnt pathway inhibitors (sclerostin) levels are associated with a reduced bone mineral density and increased risk of osteoporotic fracture. Whether oxidative stress and the Wnt pathway are related to fracture risk is poorly understood. M&M: Cross-sectional study in 21 subjects divided into three groups: seven osteoporotic hip fracture (age: 75±5) (OP); eight osteoarthritis, undergoing hip replacement, (71±4) (OA) and six OA ≤ 55 years old. We carried out hip BMD (DXA-Hologic Discovery) and microstructural and biomechanical characteristics of trabecular bone (Micro-CT-Scan Sky 1172). In macerated trabecular bone, we quantified gene expression of catalase, GADD45 (oxidative stress genes), connexin 43, cyclin D1 (Wnt pathway genes), Runx2, osteoprotegerin (OPG) and sclerostin (SOST) by qPCR. The results are analyzed statistically with the Kruskal–Wallis and Dunn’s post hoc and correlations by Pearson coefficient (SPSS 22.0), P≤ 0.05. Results: Osteoporotic subjects have an increased expression of catalase and GADD45 in trabecular bone, suggesting increased oxidative stress in these patients regardless of age and sex. We also observed a significant increase in the expression of genes involved in the Wnt pathway, connexin 43 and cyclin D1, Runx2 and OPG, in OP group. We found no differences in the SOST gene expression. As expected, BMD values are statistically lower in the OP subjects and they have a worse biomechanic and microstructure bone. Conclusion: These results suggest that the trabecular bone from patients with osteoporosis have a higher activity of oxidative stress and alterations in the Wnt pathway and osteogenic genes expression.

Osteoporosis is a metabolic disorder characterized by a reduction in bone mass and deterioration in the microarchitectural structure of the bone, leading to a higher risk for spontaneous and fragility fractures.

A prospective study was performed to compare the prevalence of morphometric vertebral fractures (MVF) between patients with inflammatory bowel disease (IBD) and healthy subjects and to identify predictive factors of fracture.