Browsing by Subject "bone density"

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    A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD
    (Published article can be found at: http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2089/abstract doi: 10.1002/jbmr.2089, 2013-09-03) Moe, Sharon M.; Chen, Neal X.; Newman, Christopher L.; Gattone II, Vincent H.; Organ, Jason M.; Chen, Xianming; Allen, Matthew R.
    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.
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    Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2−/− mice
    (2007-09) Gil-Henn, Hava; Destaing, Olivier; Sims, Natalie A; Aoki, Kazuhiro; Alles, Neil; Neff, Lynn; Sanjay, Archana; Bruzzaniti, Angela; De Camilli, Pietro; Baron, Roland; Schlessinger, Joseph
    The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2−/− mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions.