Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Study of bone mass in young daughters of women with fracture of the distal end of the radius.

The main aim was to assess whether young and healthy daughters of women with fractures of the distal end of the radius (DER) had less bone mass than the control group. In an observational study of cases and controls (1:1), the daughters of women with fractures of DER (96) were selected at the age of reaching the peak of bone mass and compared with a control group (91). All women underwent medical history, analytical determinations, and densitometry. In the case group, we found lower bone mass values at the spine and femoral neck than the control group. We also found a lower bone mass at the hips of daughters of women with 1 or more osteoporotic fractures associated with DER and at the lumbar spine in those whose mothers had densitometric osteoporosis. In conclusion, young daughters of women with fractures of DER had lower levels of bone mass density, with a possible "location-specific" occurrence based on the presence of 1 or more osteoporotic fractures associated with DER or on the presence of maternal densitometric osteoporosis.