Effect of combined treatment with zoledronic acid and parathyroid hormone on mouse bone callus structure and composition.

作者: Michele Casanova , Janelle Herelle , Marcel Thomas , Rowan Softley , Aaron Schindeler

DOI: 10.1016/J.BONE.2016.08.012

关键词:

摘要: In recent years, great interest in combined treatment of parathyroid hormone (PTH) with anti-resorptive therapy has emerged. PTH been suggested to aid bridging atrophic fractures and improve strength closed fracture models. Bisphosphonate treatments typically result a larger woven bone callus that is slower remodel. The combination both drugs demonstrated be effective for the osteoporotic loss many preclinical studies. However, effect on repair still largely unexplored. this study, we aimed compare these as single-agent murine model. We wanted assess potential differences material properties, morphometry development lacuno-canalicular network. A total 40 female, 11-week-old wild type mice underwent midshaft tibia were assigned four groups (n=8-10 per group). Beginning post-operative day 8, animals received different subcutaneous injections. Group 1 single injection saline solution 2 zoledronic acid (ZA). 3 daily dosing PTH. 4 dual treatment, starting dose ZA followed by Three weeks after fracture, all euthanized tibiae assessed using micro-computed tomography (micro-CT), high-resolution micro-CT (HR micro-CT), Raman spectroscopy, quantitative histomorphometry, deconvolution microscopy (DV microscopy). Combined showed significant increase 41% volume fraction decrease 61% standard deviation trabecular spacing compared vehicle, known strong predictors strength. An analysis via HR similar results lacunar numerical density, whereas mean lacuna was found higher vehicle treated groups, but only mono-treatment (+45%). spectroscopy did not reveal detectable changes properties calluses. Sclerostin staining, tartrate resistant phosphatase (TRAP) staining canalicular DV subset samples display distinctive difference any treatments. therefore consider PTH+ZA beneficial healing. No clear negative quality detected during study.

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