Osteoporosis: Pathophysiology and therapeutic options.

Osteoporosis is a metabolic bone disease that, on a cellular level, results from osteoclastic bone resorption not compensated by osteoblastic bone formation. This causes bones to become weak and fragile, thus increasing the risk of fractures. Traditional pathophysiological concepts of osteoporosis focused on endocrine mechanisms such as estrogen or vitamin D deficiency as well as secondary hyperparathyroidism. However, research over the last decades provided exiting new insights into mechanisms contributing to the onset of osteoporosis, which go far beyond this. Selected mechanisms such as interactions between bone and the immune system, the gut microbiome, and cellular senescence are reviewed in this article. Furthermore, an overview on currently available osteoporosis medications including antiresorptive and bone forming drugs is provided and an outlook on potential future treatment options is given.

Inflatable multichannel rectal applicator for adaptive image-guided endoluminal high-dose-rate rectal brachytherapy: design, dosimetric characteristics, and first clinical experiences.

PURPOSE: To investigate the dosimetric results and first clinical experiences with a new designed balloon applicator with adjustable catheters for endoluminal brachytherapy for patients with locally advanced rectal cancer not undergoing surgery. MATERIAL AND METHODS: The applicator consists of an inflatable rectal balloon with six attached Foley catheters used as guidance for the inserted brachytherapy plastic needles. The construction of the applicator and the dosimetric profile in terms of representative dose points in 0, 2, 5, 10 mm ipsilaterally and in 0 mm contralaterally are described. The first clinical outcomes in three patients are reported. RESULTS: For all three patients, a reproducible dose gradient was achieved. The surface dose on the target side was 204 ± 19% of the normalized dose in 5 mm (100%) tissue depth, and 143 ± 8% in 2 mm and 64 ± 3% in 10 mm tissue depth, while the surface dose on the contra-lateral side was 20 ± 8%. After radiochemotherapy with 50 Gy external beam radiotherapy and concomitant administration of capecitabine, a HDR brachytherapy boost in 2-3 fractions of 7-10 Gy each was delivered. All patients achieved a clinical complete response 3 month after the treatment, and no major toxicity was observed. CONCLUSION: The use of the applicator was clinically feasible, and resulted in a stable and reproducible dose distribution. First clinical results are promising.

Biogerontology in Austria.

In Austria significant progress in the field of biogerontology has been achieved in the past years. Biogerontological research is performed in academic and extramural institutions. The Institute for Biomedical Aging Research of the Austrian Academy of Science at Innsbruck is the largest institution dealing with biogerontology in Austria. Moreover, gerontologic research is performed at the Universities of Salzburg and Graz, the Medical Universities of Vienna, Innsbruck and Graz, the University of Veterinary Medicine (Vienna) and the University of Natural Resources and Applied Life Sciences (Vienna). This article describes the work of selected research groups involved in biogerontology in a geographic arrangement.

Pharmacologic undertreatment of osteoporosis in Austrian nursing homes and senior's residences.

Osteoporosis is a classical age-related disease. Although significant progress in treatment has been achieved and antifracture efficacy proven over the past years undertreatment is still a general problem. There are only few published data available regarding osteoporosis and its treatment encountered in Austrian nursing homes and seniors' residences where fractures are especially frequent. We therefore conducted a survey in 89 participating institutions in order to assess frequency of documented osteoporosis as well as prevalence status of anti-osteoporotic drug usage in this special population. Data were acquired using a questionnaire and analyzed in a descriptive manner. Mean age of the residents was 82 years and the majority was female (76%). Half of the subjects took 5-8 different drugs per day and 23% received more than 8. Almost one-fourth (21.2%) of the residents had a diagnosis of osteoporosis. A history of hip fracture or other fractures was documented in 10.4% and 13.2%, respectively. Only 8.2% of the residents were treated with calcium, 6.2% with vitamin D and 9.3% received a combination of vitamin D and calcium. Specific osteoporosis treatment was prescribed to 7.2% only. In conclusion, this study reflects a high degree of continuing unawareness toward a diagnosis of osteoporosis in Austrian nursing homes and seniors' residences. The data of this survey further indicate that undertreatment is still very common in this population at very high risk of fractures.

Cytokine profiling of human peripheral blood CD4+ T lymphocytes reveals a new Th-subpopulation (Th6) characterized by IL-6.

The number of functional subsets of CD4+ T lymphocytes distinguished by their cytokine production has been extended in the last decade. The in vitro generation of a T cell subset characterized by IL-6 production has resurrected the question of cytokine co-expression patterns in T cells. In order to delineate these cells as a specific functional subpopulation in vivo, we profiled the cytokine production pattern of human peripheral blood CD4+ T lymphocytes across established subsets. We provide evidence for a new T cell subset Th6, with an IL-6 signature. Freshly isolated PBMC were analyzed using intracellular cytokine detection (IDC). Cytokine co-expression patterns of up to three cytokines, as well as their correlation with selected transcription factors, were determined in CD4+ T lymphocytes. Co-expression of two of these signature cytokines used for the definition of functional subsets, e.g. IL-4, IFN-gamma, IL-17 and IL-6 were observed, but nearly excluded the production of a third (or fourth) signature cytokine. In this respect, Th1 (key cytokine IFN-gamma), Th2 (IL-4), Th6 (IL-6) and Th17 (IL-17) subsets can be defined, along with overlaps of any two of them. In contrast, TNF-alpha and IL-2 are not signature cytokines, but their absence or expression in single cells introduces further divisions across established subsets. Our study supports the concept of a further functional T cell Th6 subset, and contributes to the reference cytokine profiles of healthy individuals relevant to further studies in a variety of disease states.