Seven diphosphonate analogs were treated for their effects on myocardial and cardiovascular degeneration and calcification in an experimental model of cardiac
calciphylaxis. A single oral dose of
dihydrotachysterol (DHT) administered to rats induced myocardial and vascular degeneration, focal
myocarditis and
vasculitis, and myocardial and vascular mineralization. The results demonstrated a considerable variation among the various
diphosphonates in their ability to block the pathological changes observed in this model. Ethane-1-hydroxy-1,1-diphosphonate (
EHDP) was the most effective diphosphonate in reducing myocardial and vascular degeneration and calcification, whereas
diphosphonates such as ethane-1-amino-1,1-diphosphonate (EADP) and hydroxymethylene diphosphonate (HMDP) had little or no effect compared to saline controls. For those
diphosphonates which were effective, e.g.,
EHDP, the tissue-protective effects were observed whether the rats were treated with
drug prior to the administration of DHT, or whether
drug treatment commenced after DHT administration. The results are discussed in terms of the known
biological properties of the diphosphonate drugs.