Reduced Sirtuin1 expression at the femoral neck in women who sustained an osteoporotic hip fracture.

UNLABELLED: To investigate the role of Sirtuin1 in osteoporosis, Sirtuin1 was determined at the femoral neck in female patients undergoing hip operation for fractured hip or osteoarthritis. Reduced Sirtuin1 was found in osteoporotic patients. Pharmacologic activation of Sirtuin1 reduced sclerostin, an inhibitor of bone formation. Activation of Sirtuin1 may be a new direction to generate therapies for osteoporosis. INTRODUCTION: The aim of the study are to investigate the role of Sirtuin1 (Sirt1), an anti-aging factor and a player in age-associated diseases, in osteoporotic hip fractures, and test the hypothesis that Sirt1 is a negative regulator of sclerostin, a bone formation inhibitor, in human femoral bone marrow mesenchymal cells (BM-MSCs). METHODS: Sirt1 and sclerostin were determined by western blot in bone samples obtained intra-operatively from the inferior medial cortex of the femoral neck (calcar region) in female patients undergoing partial hip replacement for fractured neck of femur (N = 10) or hip replacement for osteoarthritis (N = 8) (mean ± SD age 81 ± 8.1 vs. 68 ± 9.3 years; BMI 26.2 ± 3.6 vs. 25.9 ± 7.1 kg/m(2) in osteoporotic and osteoarthritis patients). Calcar thickness and femoral bone mineral density (BMD) were determined preoperatively by X-ray using a digital TraumaCad(™) software and DEXA. Femoral BM-MSCs were collected intra-operatively and treated with SRT3025, a Sirt1 activator. Sclerostin and dentin matrix acidic phosphoprotein (DMP1) were determined by western blot and messenger RNA (mRNA) expression of Lef1 and DMP1 was evaluated by quantitative real-time PCR. RESULTS: Osteoporotic (OP) patients had reduced cortical thickness, femoral neck, and total hip BMD compared to osteoarthritis (OA) patients. Calcar Sirt1 expression was significantly reduced, while sclerostin was markedly increased in OP compared to OA patients. Sirt1 and sclersotin expressions were inversely correlated (r = -0.49, P = 0.047). SRT3025 administration down-regulated sclerostin and up-regulated DMP1 protein level and increased LEF1 and DMP1 mRNA expressions in OP patient-derived BM-MSCs. CONCLUSIONS: Reduced femoral neck Sirt1 may play a role in osteoporotic hip fractures in part via influencing local sclerostin expression. The therapeutic potential of Sirt1 activation in osteoporosis warrants further investigation.

Prevalence of torus palatinus in a population of young and adult Israelis.

The prevalence of torus palatinus, a common exostosis with a debatable pathogenesis, was epidemiologically investigated in a group of 1002 Israeli Jews. This protuberance was observed in 21% of the entire sample, with non-significant differences among different age groups. The smooth type of torus was noted in 72.9%, 68.1% were smaller than 2 cm, and 53.8% were located in the molar area only. The prevalence of torus palatinus in the combined molar-premolar area increased with age, whereas in the molar area it decreased, expressing a significant relation between location and age (p < 0.01). The prevalence of tori larger than 2 cm was much higher in the 21-year and older age groups than in the younger groups. The diverse prevalence of torus palatinus in some of the ethnic groups was also statistically significant (p < 0.05). The aetiology of this common osseous outgrowth is probably multifactorial, including environmental factors acting in a complicated and unclear interplay with genetic factors.