Didronel acts primarily on bone. It can inhibit the formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces. Inhibition of crystal resorption occurs at lower doses than are required to inhibit crystal growth. Both effects increase as the dose increases.

Didronel is not metabolized. The amount of drug absorbed after an oral dose is approximately 3%. In normal subjects, plasma half-life (t_1/2) of etidronate, based on non- compartmental pharmacokinetics is 1 to 6 hours. 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. Animal studies have yielded bone clearance estimates up to 165 days. In humans, the residence time on bone may vary due to such factors as specific metabolic condition and bone type. Unabsorbed drug is excreted intact in the feces. Preclinical studies indicate etidronate disodium does not cross the blood-brain barrier.

Didronel therapy does not adversely affect serum levels of parathyroid hormone or calcium.

Paget's Disease: Paget's disease of bone (osteitis deformans) is an idiopathic, progressive disease characterized by abnormal and accelerated bone metabolism in one or more bones. Signs and symptoms may include bone pain and/or deformity, neurologic disorders, elevated cardiac output and other vascular disorders, and increased serum alkaline phosphatase and/or urinary hydroxyproline levels. Bone fractures are common in patients with Paget's disease.

Didronel slows accelerated bone turnover (resorption and accretion) in pagetic lesions and, to a lesser extent, in normal bone. This has been demonstrated histologically, scintigraphically, biochemically, and through calcium kinetic and balance studies. Reduced bone turnover is often accompanied by symptomatic improvement, including reduced bone pain. Also, the incidence of pagetic fractures may be reduced, and elevated cardiac output and other vascular disorders may be improved by Didronel therapy.

Heterotopic Ossification: Heterotopic ossification, also referred to as myositis ossificans (circumscripta, progressiva or traumatica), ectopic calcification, periarticular ossification, or paraosteoarthropathy, is characterized by metaplastic osteogenesis. It usually presents with signs of localized inflammation or pain, elevated skin temperature, and redness. When tissues near joints are involved, functional loss may also be present.

Heterotopic ossification may occur for no known reason as in myositis ossificans progressiva or may follow a wide variety of surgical, occupational, and sports trauma (e.g., hip arthroplasty, spinal cord injury, head injury, burns, and severe thigh bruises). Heterotopic ossification has also been observed in non-traumatic conditions (e.g., infections of the central nervous system, peripheral neuropathy, tetanus, biliary cirrhosis, Peyronie's disease, as well as in association with a variety of benign and malignant neoplasms).

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