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Der Einfluss von Therapie und Prophylaxe mit Strontiumranelat auf das proximale Femur osteoporotischer Ratten

dc.contributor.advisorTezval, Mohammad PD Dr.
dc.contributor.authorKöstner, Felix
dc.date.accessioned2020-01-27T09:32:19Z
dc.date.available2020-02-04T23:50:02Z
dc.date.issued2020-01-27
dc.identifier.urihttp://hdl.handle.net/21.11130/00-1735-0000-0005-12FB-C
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-7795
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc610de
dc.titleDer Einfluss von Therapie und Prophylaxe mit Strontiumranelat auf das proximale Femur osteoporotischer Rattende
dc.typedoctoralThesisde
dc.title.translatedThe influence of therapy and prophylaxis with strontium ranelate on proximal femur of osteoporotic ratsde
dc.contributor.refereeSeidlova-Wuttke, Dana PD Dr.
dc.date.examination2020-01-28
dc.description.abstractengIntroduction: Osteoporosis is defined as a systemic skeletal disease characterized by loss of bone mass and a reduction in the microarchitecture of bone tissue. Due to increasing numbers of cases and high socio-economic burden, the research of drug-based treatment approaches is gaining importance worldwide. Several drugs are currently approved for therapy. Strontiumranelate (SR) has a special position, as it not only stimulates bone formation but also inhibits bone resorption. The main objective of this study was to analyze the effect of SR therapy in ovariectomized (OVX) rats on the development of osteoporosis in the proximal femur. Methods: For our study three-month-old Sprague-Dawley rats were divided into two groups: 48 animals were ovariectomized, twelve animals remained untreated (control group 1). As expected, the ovariectomized animals developed osteoporosis after 8 weeks. After another five weeks the trial ended. All OVX animals had been subdivided (n= 12 per group) and treated group-specifically with SR:  2) OVX (ovariectomy only), 3) SR th (SR as osteoporosis therapy over 5 weeks), 4) SR pr (SR as osteoporosis prophylaxis over 8 weeks), 5) SR pr + th (SR as prophylaxis and therapy over 13 weeks). The groups treated with SR received it as a feed supplement at an average dosage of 654 mg/kg body weight/day during this period. After the end of the trial, the femora of the rats were dissected and analyzed by biomechanical compression tests, microradiography and incineration. Results: The evaluation could not demonstrate any effect of SR on the biomechanical parameters of the osteoporotic femora. In microradiography, a positive effect of SR on the microarchitecture of trabecular bone was observed. Long-term prophylactic treatment (SR pr+th) over 13 weeks was able to improve trabecular bone, increase number of trabecular nodes and trabecular density compared to the OVX group, achieving nearly as good values as in the bone of the control group. A prophylactic treatment over eight weeks (SR pr) was able to reduce bone resorption from the beginning of the hormone deficiency period. Short-term treatment over five weeks (SR th) also showed a slight improvement in the microarchitecture of the trabecular structures. SR could be detected in bone both directly and indirectly in all treatment groups. It was indirectly demonstrated that strontium was stored in the bone but through this there was no significant loss of calcium in the bone tissue. The determination of calcium and phosphate in the bone showed a tendency for a loss of the mineral salt content in the OVX group because of the osteoporosis development. However, all SR treated groups showed no significant changes in this respect compared to the control group. Conclusion: In our study a treatment with SR for 13 weeks could partially protect the trabecular bone density from osteoporotic decay. The quality of the trabecular structure could be maintained by SR approximately at the level of healthy control animals. Strontium could be stored in the bone and a loss of mineral salt content due to the osteoporosis could be prevented by SR treatment (SR pr, SR th, SR pr+th). The SR treatments, however, had no biomechanical advantage. It can be assumed that SR was able to have a longer lasting positive effect on the bone even after the end of the treatment (SR pr). The positive effect was probably also due to the certain resorption-inhibiting effect in the first weeks of treatment, because SR was able to prevent bone loss occurred after OVX. The duration of the after-effect should be further investigated. The lowest effect was shown by SR therapy form over a period of five weeks. Thus, the short SR treatment is not sufficient to treat severe osteoporosis and must be performed over the longer period.de
dc.contributor.coRefereeOppermann, Martin Prof. Dr.
dc.subject.gerOsteoporosede
dc.subject.gerStrontiumranelatde
dc.subject.gerproximaler Rattenfemurde
dc.subject.gertrabekulärer Knochende
dc.subject.engosteoporosisde
dc.subject.engstrontium ranelatede
dc.subject.engproximal femur of the ratde
dc.subject.engtrabecular bonede
dc.subject.engbone tissuede
dc.subject.engovariectomyde
dc.identifier.urnurn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-12FB-C-0
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullGOK-MEDIZINde
dc.description.embargoed2020-02-04
dc.identifier.ppn1688630295


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