No abstract

Patients with chronic kidney disease (CKD) have increased risk of fractures, yet the optimal treatment is unknown. In secondary analyses of large randomized trials, bisphosphonates have been shown to improve bone mineral density and reduce fractures. However, bisphosphonates are currently not recommended in patients with advanced kidney disease due to concern about over-suppressing bone remodeling, which may increase the risk of developing arterial calcification. In the present study we used a naturally occurring rat model of CKD with secondary hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with zoledronic acid, calcium given in water to simulate a phosphate binder, and the combination of calcium and zoledronic acid. Animals were treated beginning at 25 weeks of age (approximately 30% of normal renal function) and followed for ten weeks. The results demonstrate that both zoledronic acid and calcium improved bone volume by microCT and both equally suppressed mineral apposition rate, bone formation rate, and mineralizing surface of trabecular bone. In contrast, only calcium treatment with or without zoledronic acid improved cortical porosity and cortical biomechanical properties (ultimate load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium treatment led to the adverse effects of increased arterial calcification and fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may improve trabecular bone volume in CKD in the presence of secondary hyperparathyroidism, but does not benefit extraskeletal calcification or cortical biomechanical properties. Calcium effectively reduces PTH and benefits both cortical and trabecular bone yet increases the degree of extra skeletal calcification.

No abstract

Chronic Kidney Disease (CKD) is associated with abnormalities in bone quantity and quality leading to increased fractures. Recent studies suggest abnormalities of Wnt signaling in animal models of CKD and elevated sclerostin levels in patients with CKD. The goal of this study was to evaluate the effectiveness of anti-sclerostin antibody treatment in an animal model of progressive CKD with low and high parathyroid hormone (PTH) levels. Cy/+ male rats (CKD) were treated without or with calcium in the drinking water at 25 weeks of age to stratify the animals into high PTH and low PTH groups, respectively, by 30 weeks. Animals were then treated with anti-sclerostin antibody at 100 mg/kg IV weekly for 5 doses, a single 20 ug/kg subcutaneous dose of zoledronic acid, or no treatment and sacrificed at 35 weeks. As a positive control, the efficacy of anti-sclerostin antibody treatment was also evaluated in normal littermates. The results demonstrated that the CKD animals with high PTH had lower calcium, higher phosphorus, and lower FGF23 compared to the CKD animals with low PTH. Treatment with anti-sclerostin Ab had no effect on any of the biochemistries, while zoledronic acid lowered dkk-1 levels. The anti-sclerostin antibody increased trabecular BV/TV., trabecular mineralization surface, in animals with low, but not high, PTH. Neither anti-sclerostin antibody nor zoledronic acid improved biomechanical properties in the animals. Cortical porosity was severe in high PTH animals and unaffected by either treatment. In contrast, in normal animals treated with anti-sclerostin antibody, there was an improvement in bone volume, cortical geometry, and biomechanical properties. In summary, this is the first study to test the efficacy of anti-sclerostin Ab treatment on animals with advanced CKD. We found efficacy in improving bone properties only when the PTH levels were low.

Purpose Mobile apps represent an emergent self-service technology that has greatly contributed to the rise of mobile shopping. However, the existing services and marketing literature offer little insight on consumer app usage. Further, little is known about how this app usage might affect important outcomes such as consumers’ intentions to use and recommend an app, their channel preferences (in-store vs app), or their purchasing behavior with the app. Thus, the purpose of this research is to examine if, and how, consumers’ actual experiences using retailers’ apps affected these outcomes. Design/methodology/approach Data were collected from a series of online surveys of adult consumers based on their prior experiences with retailers’ apps. The hypothesized relationships were tested using regression analyses. Findings Results highlight perceived ease of use as a critical app attribute that fosters consumers’ personal connections to apps. These connections in turn influence their purchase channel preferences (app vs in-store) and actual purchasing behavior with the app, as well as their future intentions to purchase with the app and recommend it to others. App usage frequency is shown to moderate these effects. Research limitations/implications The findings provide needed managerial insight into consumer usage of brick-and-click retailers’ apps. Specifically, the results inform service providers’ mobile commerce strategies – particularly with respect to app design, channel management and customer segmentation. Future opportunities exist to explore and compare consumer usage of other types of service providers’ apps, such as “pure play” providers that do not have physical stores. Originality/value This research moves beyond initial app adoption to instead focus on consumers’ actual app usage experiences and their implications. Of note, the findings suggest that firms may be paradoxically driving consumers away from their physical stores as they continue to devote considerable resources to creating and providing customers with easy-to-use mobile apps.