The effects of various diphosphonates on a rat model of cardiac calciphylaxis

Abstract

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.

Suppression of experimental atherosclerosis by the Ca++-antagonist lanthanum. Possible role of calcium in atherogenesis.

“…These compounds exerted their antiatherosclerotic effect despite unmitigated high serum cholesterol levels when given in large enough amounts. Similar protective actions of diphosphonic acids also have been reported by others (8)(9)(10)(11) in animal models of atheroarteriosclerosis. In addition, other drugs that inhibit arterial deposition of calcium or its use also have been shown to be antiatherogenic.…”

Cartilage Dysplasia and Tissue Mineralization in the Rat Following Administration of a FGF Receptor Tyrosine Kinase Inhibitor

“…Tissue mineralization in rats following administration of PD176067 is similar to vitamin D toxicity due to dysregulation in serum calcium (Ca) and phosphorus (P) homeostasis (Grant et al, 1963; Rosenblum et al, 1977; Kamio et al, 1979; Mortensen et al, 1996). Markedly elevated levels of serum phosphorus were seen in mature rats at 10 mg/kg (increased 166%), and serum calcium was slightly increased at this dose.…”

Review: Vascular calcification in chronic kidney disease: the tip of the chalk-berg

“…There are only a few studies that have evaluated additional agents to help retard or regress vascular calcification in patients with renal failure. Some interventions that have been evaluated include bisphosphonates [22][23][24] and calcium-channel blockers. 25 One small study also found that subtotal parathyroidectomy significantly decreased or stabilised vascular calcification.…”