| Indication | For the treatment of symptomatic Paget's disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury. |
| Pharmacodynamics | Etidronic acid is a first generation (non-nitrogenous) bisphosphonate in the same family as clodronate and tiludronate. Etidronic acid affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the etidronic acid that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Etidronic acid has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia. |
| Mechanism of action | Bisphosphonates, when attached to bone tissue, are absorbed by osteoclasts, the bone cells that breaks down bone tissue. Although the mechanism of action of non-nitrogenous bisphosphonates has not been fully elucidated, available data suggest that they bind strongly to hydroxyapatite crystals in the bone matrix, preferentially at the sites of increased bone turnover and inhibit the formation and dissolution of the crystals. Other actions may include direct inhibition of mature osteoclast function, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation. Etidronic acid does not interfere with bone mineralization. In malignancy-related hypercalcemia, etidronic acid decreases serum calcium by inhibiting tumour-induced bone resorption and reducing calcium flow from the resorbing bone into the blood. Etidronic acid also reduces morbidity of osteolytic bone metastases by inhibiting tumour-induced bone resorption. Etidronic acid may promote osteoclast apoptosis by competing with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. |
| Absorption | The amount of drug absorbed after an oral dose is approximately 3%. |
| Volume of distribution | Not Available |
| Protein binding | Not Available |
| Metabolism | Not metabolized. |
| Route of elimination | Etidronate disodium is not metabolized. Within 24 hours, approximately half the absorbed dose is excreted in urine; the remainder is distributed to bone compartments from which it is slowly eliminated. Unabsorbed drug is excreted intact in the feces. |
| Half life | In normal subjects, plasma half-life of etidronic acid, based on non-compartmental pharmacokinetics is 1 to 6 hours. |
| Clearance | Not Available |
| Toxicity | Clinical experience with acute etidronic acid overdosage is extremely limited. Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients. Some patients may develop vomiting. In one event, an 18-year-old female who ingested an estimated single dose of 4800 to 6000 mg (67 to 100 mg/kg) of etidronate was reported to be mildly hypocalcemic (7 .5 2 mg/ dl) and experienced paresthesia of the fingers. |