Advancing Methods of Assessing Bone Quality to Expand Screening for Osteoporosis.

CONTEXT: Dual-energy x-ray absorptiometry (DXA) limits osteoporosis screening because of machine size, technical requirements for operation, and exposure to ionizing radiation. OBJECTIVE: To establish data ranges from calcaneus ultrasonography (US) that correspond to bone mineral density (BMD) stratification identified by DXA and to determine whether vitamin D concentration adds to US bone health assessment. METHODS: Patients scheduled for DXA at the Robert C. Byrd Clinic, a rural primary care facility in Lewisburg, West Virginia, were recruited from June 2015 to June 2016. Ultrasonography was used to scan the left and right calcaneus of the patients, and blood was collected from a finger prick for vitamin D analysis. Information was collected regarding Fracture Risk Assessment tool parameters, menstrual history, and drug and supplement use. The correlations within and between DXA and US measurements were calculated, as well as the correlations between DXA and US measurements and vitamin D levels. Predictive performance of US readings on bone health determined by DXA scan was assessed with area under the curve analysis using receiver operator characteristic curves. RESULTS: Ninety-nine participants were included. Ultrasonography readings of either the left or right foot were predictive of good vs poor bone quality. No differences were found between US scans of the left foot vs the right foot. Area under the curve values for US BMD T scores for the left and right foot were 0.69 and 0.68, respectively. There was no correlation between DXA- and US-assessed BMD and vitamin D concentrations. Negative correlations were observed between the DXA BMD T scores and vitamin D concentration of the spine and right hip; negative correlations were also observed in the Z score from the spine in the subset of participants who reported not taking vitamin D supplements. CONCLUSION: Ultrasonography of the calcaneus offers a low-cost, efficient means to screen bone health. The affordability and mobility of a US machine enables its use as a screening method that may be applicable to large numbers of people. This study established a T score greater than -1.05 as an indicator of good bone quality and a T score less than -1.05 as an indicator of poor bone quality when using US for BMD screening.

Polyene-based cationic lipids as visually traceable siRNA transfer reagents.

Cationic lipids are promising non-viral vectors for the cellular delivery of nucleic acids. Important considerations for the development of new delivery vectors are enhanced uptake efficiency, low toxicity and traceability. Traceable gene transfer systems however typically require the inclusion of a labeled excipient, and highly sensitive imaging instrumentation to detect the presence of the label. Recently, we reported the synthesis and characterization of colored, polyene cationic phospholipidoids composed of a rigid, polyenoic acid of predetermined dimension (C20:5 and C30:9) paired with flexible saturated alkyl chains of varying lengths (12:0, 14:0, 16:0, 18:0, 20:0 carbons). Herein, the potential of these cationic phospholipids as siRNA carriers was evaluated through standard liposomal formulations in combination with a neutral helper lipid DOPE. The polyene-based lipids were compared with a standard cationic lipid for siRNA-delivery into luciferase expressing HR5-CL11 cells. Within the series of lipids screened, knockdown results indicated that polyene cationic phospholipids paired with longer saturated alkyl chains are more effective as gene transfer agents, and perform comparably with the commercial lipid EPC. Furthermore, the chromophore associated with the polyene chain allowed tracking of the siRNA delivery using direct observation. The polyene lipoplexes were tracked on both a macroscopic and microscopic level either as a single-component or as a multi-component lipoplex formulation. When combined with a reference EPC, effective knockdown and tracking abilities were combined in a single preparation.