Osteoporosis Imaging.

Osteoporosis is the most common disease affecting bones worldwide. Dual x-ray absorptiometry (DXA) is the current reference standard for assessing bone health and, combined with other clinical parameters, provides a good estimation of fracture risk. DXA-based Trabecular Bone Score (TBS) can provide complementary indirect information about bone microarchitecture, which also deteriorates osteoporosis. QCT can provide a 3-D volumetric assessment of bone mineral density (BMD), and FEA of computed tomography (CT) images of bone can provide estimates of bone strength, which have the potential to add value, beyond BMD, for fracture risk assessment. Magnetic resonance imaging (MRI) of bone microarchitecture is an additional promising alternative to the assessment of BMD, and there is evidence that microarchitectural parameters could 1 day have benefits for diagnosing osteoporosis beyond BMD and/or FRAX. Assessment of bone via MRI also provides insight into other bone tissue properties (cortical porosity, marrow fat) that are altered in osteoporosis and that DXA cannot assess. Overall, bone health cannot be characterized solely by one parameter. Current imaging techniques/modalities in combination with advanced image processing hold the potential to provide a comprehensive understanding of the pathologic changes that occur in bone tissue in the setting of osteoporosis and pave the way for new imaging methods to diagnose, monitor, and predict osteoporosis.

Cost-effectiveness of Virtual Bone Strength Testing in Osteoporosis Screening Programs for Postmenopausal Women in the United States.

Purpose To investigate whether assessment of bone strength with quantitative computed tomography (CT) in combination with dual-energy x-ray absorptiometry (DXA) is cost-effective as a screening tool for osteoporosis in postmenopausal women. Materials and Methods A state-transition microsimulation model of osteoporosis for postmenopausal women aged 55 years or older was developed with a lifetime horizon and U.S. societal perspective. All model inputs were derived from published literature. Three strategies were compared: no screening, DXA with T score-dependent rescreening intervals, and a combination of DXA and quantitative CT with different intervals (3, 5, and 10 years) at different screening initiation ages (55-65 years). Oral bisphosphonate therapy was started if DXA hip T scores were less than or equal to -2.5, 10-year risk for hip fracture was greater than 3% (World Health Organization Fracture Risk Assessment Tool score, or FRAX), 10-year risk for major osteoporotic fracture was greater than 20% (FRAX), quantitative CT femur bone strength was less than 3000 N, or occurrence of first fracture (eg, hip, vertebral body, wrist). Outcome measures were incremental cost-effectiveness ratios (ICERs) in 2015 U.S. dollars per quality-adjusted life year (QALY) gained and number of fragility fractures. Probabilistic sensitivity analysis was also performed. Results The most cost-effective strategy was combined DXA and quantitative CT screening starting at age 55 with quantitative CT screening every 5 years (ICER, $2000 per QALY). With this strategy, 12.8% of postmenopausal women sustained hip fractures in their remaining life (no screening, 18.7%; DXA screening, 15.8%). The corresponding percentages of vertebral fractures for DXA and quantitative CT with a 5-year interval, was 7.5%; no screening, 11.1%; DXA screening, 9%; for wrist fractures, 14%, 17.8%, and 16.4%, respectively; for other fractures, 22.6%, 30.8%, and 27.3%, respectively. In probabilistic sensitivity analysis, DXA and quantitative CT at age 55 years with quantitative CT screening every 5 years was the best strategy in more than 90% of all 1000 simulations (for thresholds of $50 000 per QALY and $100 000 per QALY). Conclusion Combined assessment of bone strength and bone mineral density is a cost-effective strategy for osteoporosis screening in postmenopausal women and has the potential to prevent a substantial number of fragility fractures. © RSNA, 2017 Online supplemental material is available for this article.

Three-dimensional saturation transfer ³¹P-MRI in muscles of the lower leg at 3.0 T.

The creatine kinase (CK) reaction plays a critical role in skeletal muscle function, and can be studied non-invasively using phosphorus ((31)P) saturation transfer (ST) techniques. However, due to the low MR sensitivity of the (31)P nucleus, most studies on clinically approved magnetic fields (≤3.0 T) have been performed with coarse resolution and limited tissue coverage. However, such methods are not able to detect spatially resolved metabolic heterogeneities, which may be important in diseases of the skeletal muscle. In this study, our aim was to develop and implement a (31)P-MRI method for mapping the kinetics of the CK reaction, and the unidirectional phosphocreatine (PCr) to adenosine triphosphate (ATP) metabolic fluxes in muscles of the lower leg on a clinical 3.0 T MR scanner. We imaged the lower leg muscles of ten healthy volunteers (total experimental time: 40 min, nominal voxel sizes 0.5 mL), and found statistically significant differences between the kinetics of the CK reaction among muscle groups. Our developed technique may allow in the future the early detection of focal metabolic abnormalities in diseases that affect the function of the skeletal muscle.

Three-dimensional mapping of the creatine kinase enzyme reaction rate in muscles of the lower leg.

Phosphorus ((31) P) magnetization transfer (MT) techniques enable the non-invasive measurement of metabolic turnover rates of important enzyme-catalyzed reactions, such as the creatine kinase reaction (CK), a major transducing reaction involving adenosine triphosphate and phosphocreatine. Alteration in the kinetics of the CK reaction rate appears to play a central role in many disease states. In this study, we developed and implemented at ultra-high field (7T) a novel three-dimensional (31) P-MT imaging sequence that maps the kinetics of CK in the entire volume of the lower leg at relatively high resolution (0.52 mL voxel size), and within acquisition times that can be tolerated by patients (below 60 min). We tested the sequence on five healthy and two clinically diagnosed type 2 diabetic subjects. Overall, we obtained measurements that are in close agreement with measurements reported previously using spectroscopic methods. Importantly, our spatially resolved method allowed us to measure local CK reaction rate constants and metabolic fluxes in individual muscles in a non-invasive manner. Furthermore, it allowed us to detect variations of the CK rates of different muscles, which would not have been possible using unlocalized MRS methods. The results of this work suggest that 3D mapping of the CK reaction rates and metabolic fluxes can be achieved in the skeletal muscle in vivo at relatively high spatial resolution and with acquisition times well tolerated by patients. The ability to measure bioenergetics simultaneously in large areas of muscles will bring new insights into possible heterogeneous patterns of muscle metabolism associated with several diseases and serve as a valuable tool for monitoring the efficacy of interventions.

Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione from coffee extract.

It has been known that reactive oxygen and nitrogen species such as nitric oxide (NO), superoxide radical (*O2-) and their byproduct peroxynitrite (ONOO-) induce cellular and tissue injury, ultimately resulting in several human diseases. In this study, we examined scavenging effects of 3-methyl-1,2-cyclopentanedione (MCP) from coffee extract on the reactivity of those toxic molecules. MCP significantly inhibited both the oxidation of 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) by reactive oxygen species (ROS) (mainly *O2-) from kidney homogenate (41% at 100 microM) and the generation of fluorescent 4,5-diaminofluorescein (DAF-2) by NO from sodium nitroprusside (IC50 (concn producing 50% inhibition), 63.8 microM). More potently, however, MCP suppressed the oxidation of dihydrorhodamine 123 (DHR 123) to fluorescent rhodamine 123 mediated by authentic ONOO- with an IC50 value of 3.3 microM. The neutralizing effect of the reactivity of ONOO- by MCP was due to electron donation, not nitration of the compound. Additionally, MCP also decreased ONOO- formation of nitrotyrosine adducts of glutathione (GSH) reductase, and consequently protected the enzyme activity of GSH reductase against decreasing by ONOO-, indicating that MCP may prevent ONOO- -induced damage of GSH reductase. Furthermore, MCP only weakly suppressed NO production, which is one of the upstream sources of ONOO- in-vivo, suggesting that NO production may be not a pharmacological target for MCP. Taken together, our results suggest that MCP may be regarded as a selective regulator of ONOO- -mediated diseases via direct scavenging activity of ONOO-.