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Schindler, Katja (2005): Untersuchungen zum therapeutischen Einsatz von Calcium und Vitamin D-Metaboliten bei herzinsuffizienten und herztransplantierten Patienten. Dissertation, LMU München: Tierärztliche Fakultät



Osteoporosis and osteopenia are frequent complications which occur after a cardiac transplantation and which are caused by the necessity of a lifetime therapy based on different immunosuppressants. In case of chronic cardiac insufficiency, however, bone metabolism disorders can be observed even before a planned heart transplantation – the pathogenesis of these symptoms is currently to a great extent uncertain. The present study examined the changes of bone metabolism in patients with heart insufficiency, at the same time it dealt with the influence of a calcium substitution with reference to a prospective osteoporosis prophylaxis. Furthermore, the effect has been studied which a prophylactic dose of vitamin D metabolite 1,25-dihydroxyvitamin D3 (0.5µg) given to heart transplanted recipients has on bone metabolism and bone mineral density. These data were compared with a study analyzing the effect of 0.25µg 1,25-dihydroxyvitamin D3 placebo-controlled and also to a study using 1α-hydroxyvitamin D3 for prevention. The present study demonstrated that in patients with chronic cardiac insufficiency a reduced bone mineral density was documented before the planned cardiac transplantation. Nearly 50% of the patients had pathological bone changes in the sense of osteopenia or osteoporosis. By means of different bone markers it has been detected that a high turnover osteoporosis uncoupled by bone formation and resorption is responsible for bone loss. Moreover, the results may lead to the conclusion that besides loop diuretics and anticoagulants the concomitant symptoms of a chronic cardiac insufficiency, strictly speaking hypogonadism, secondary hyperparathyroidism and vitamin D deficiency play a major role in bone loss. In order to create better conditions for a cardiac transplantation these risk factors must be monitored and treated adequately. With calcium substitution no significant influence on bone mineral density could be documented. Calcium prophylaxis, however, seems to have a certain inhibitory effect on bone resorption as well as on secondary hyperparathyroidism. In heart transplanted recipients who were administered 1,25-dihydroxyvitamin D3 and 1α-hydroxyvitamin D3 an increased bone mineral density and thus a normalization of the bone metabolism was observed. Treatment with 1,25-dihydroxyvitamin D3 showed an inhibitory effect of high turnover osteoporosis by means of the decreasing bone resorption and formation markers. 1α-hydroxyvitamin D3 had an inhibitory effect on bone resorption and a stimulating effect on bone formation. 1,25- dihydroxyvitamin D3 at a dosage of 0.5µg triggered hypercalcemic effects. As this higher medication has not shown superiority compared with the lower one regarding the increase of bone mineral density, the dosage of 0.25µg 1,25- dihydroxyvitamin D3 seems to have more advantages. The results of this study prompt the suggestion that the use of vitamin D metabolites is more efficient for prevention and therapy of post-transplantation osteoporosis than the sole calcium substitution. With the present study no difference could be demonstrated between the above mentioned vitamin D metabolites concerning the effect on an increase of bone mineral density. In summary, the present data show the importance of pre-operative and post-operative screening in order to detect the negative influences on bone metabolism and to treat patients with chronic heart insufficiencies and after cardiac transplantations as soon as possible.