| dc.description.abstracteng | 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
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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. | de |