Diagnostic Performance of a Panel of miRNAs (OsteomiR) for Osteoporosis in a Cohort of Postmenopausal Women.

A specific signature of 19 circulating miRNAs (osteomiRs) has been reported to be associated with fragility fractures due to postmenopausal osteoporosis. However, it is unknown whether osteoporotic fractures or low BMD phenotypes are independently contributing to changes in osteomiR serum levels. The first aim was to characterize the abundance, sensitivity to hemolysis, and correlation of osteomiR serum levels, the second objective to evaluate the diagnostic accuracy of osteomiRs for osteoporosis according to the WHO criteria and on basis of major osteoporotic fracture history. Fifty postmenopausal women with osteoporosis (with or without fragility fracture) and 50 non-osteoporotic women were included in this cross-sectional study. The diagnostic performance of osteomiRs for osteoporosis based on the WHO definition or fracture history was evaluated using multiple logistic regression and receiver-operator curve (AUC) analysis. The osteomiR® signature is composed of four clusters of miRNAs providing good performance for the diagnosis of osteoporosis in postmenopausal women defined by WHO criteria (AUC = 0.830) and based on history of major osteoporotic fractures (AUC = 0.834). The classification performance for the WHO criteria and for fracture risk is driven by miR-375 and miR-203a, respectively. OsteomiRs, a signature of 19 emerging miRNA bone biomarkers, are measurable in human serum samples. They constitute a panel of independent bone and muscle biomarkers, which in combination could serve as diagnostic biomarkers for osteoporosis in postmenopausal women.

Poly(ethylene carbonate) microspheres: manufacturing process and internal structure characterization.

The granulocyte-macrophage colony stimulating factor (GM-CSF), a water-soluble cytokine, was encapsulated in poly(ethylene carbonate) microspheres (MS) by a double emulsion w(1)/o/w(2) solvent evaporation method. Poly(ethylene carbonate) is a new polymer of high molecular weight (MW) and forms polymer matrices that are exclusively surface bioerodible. In the frame of this study, the influence of the polymer molecular weight and the polymer concentration in the organic phase on the physico-chemical characteristics of the microspheres were investigated. Ninety percent of the microspheres had a diameter ranging between 4 and 136 microm, with a mean value of 30 microm. The encapsulation ratios ranged from 2.22 to 2.51% (w/w) depending on the molecular weight of the polymer corresponding to an encapsulation efficiency of 70 to 100%, respectively. Independent of the polymer molecular weight used, the in vitro drug release was very low, ranging from 5.61 to less than 1% of the total encapsulated GM-CSF amount. Scanning electron microscopy (SEM) analysis showed microparticles with spherical shapes and smooth surfaces containing a few small globules. The inner structure of the microspheres appeared to consist of a polymeric matrix surrounding numerous globules. These globules have different sizes, shape and distribution in the polymeric matrix, depending on the concentration of the polymer solution and on the polymer molecular weight. In addition, it was demonstrated that the GM-CSF lowered the interfacial tension between the GM-CSF aqueous solution and the methylene chloride organic phase. The active critical concentration was as low as 0.008 mg/ml. It was therefore suggested that this particular behavior contributed to the stabilization of the primary emulsion during the formation of the microspheres, leading to rather high encapsulation efficiency.