Effect of intermittent parathyroid hormone therapy on the lumbar spine of male rats depending on application interval

Currently, teriparatide, a recombinant form of parathyroid hormone (PTH), is usually applied once daily as a subcutaneus injection for therapeutical purposes in the treatment of osteoporosis. Object of this study was to determine, whether the application every second day can still maintain a sufficient therapeutical effect while diminishing adverse side-effects and costs. In order to study the effects of an intermittent application of PTH on the lumbar spine in a rat animal model, 48 out of 72 eight-month-old Sprague-Dawley rats were orchiectomized. After surgery, the animals were divided into three test groups (ORX) and two control groups (SHAM). During the following 12 weeks, the orchiectomized rats developed a quantitive and qualitive loss of bone in the lumbar spine, partly resembling human osteoporosis. Twelve weeks after the beginning of the experiment, standardized osteotomies of the proximal tibial metaphysis were performed with following plate osteosynthesis. Analysis of the fracture healing after these osteotomies was part of a different doctoral thesis (Brandsch 2011). Following the osteotomies, one test group and one control group were treated once daily with an subcutaneus injection of 40 μg/kg bodyweight teriparatide and another test group was treated every second day with an subcutaneus injection of 40 μg/kg bodyweight teriparatide for the next 5 weeks up to the end of the experiment. Then, all animals were sacrificed by decapitation and lumbar vertebrae were collected for further examination by biomechanical testing, ashing, microradiography and flat-panel volume computer tomography. For each group and test, at least ten animals were analyzed except for ashing, where at least six animals could be analyzed. The results for each parameter of the biomechanical compression test were correlated with the data of the other tests to uncover statistical connections. The osteoanabolic effects of the intermittent treatment with PTH which so far have been predominantly demonstrated in female test subjects could be confirmed for male rats as well. The daily administration of PTH showed to improve cortical and trabecular bone density, cortical thickness, cortical volume fraction and mean trabecular thickness, all leading to an increased fracture strength of the lumbar vertebrae of the analyzed male rats. The effects could be demonstrated for orchiectomized as well as for control animals. The present study has shown inferior effects of the prolonged application interval every second day in comparison to the daily administration, because compared with the untreated test group (ORX), no significant improvement of the biomechanical 94 parameters could be observed for the prolonged application interval in contrast to the daily administration. Considering the data of this study, with regard to the given restrictions resulting from animal models, the daily administration should be the preferred choice.2019-01-2