ETIDRONIC ACID - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC EFFICACY IN RESORPTIVE BONE-DISEASE

Etidronic acid is an orally and intravenously active bisphosphonate, w hich is believed to inhibit resorption of bone via a number of cellula r mechanisms, including alteration of osteoclastic activity. In studie s of patients with symptomatic Paget's disease, etidronic acid 5 to 20 mg/kg/day administered orally rapidly decreased the biochemical indic es of bane turnover. Mineralisation defects in forming bone may be avo ided by the use of an initial dosage of 5 mg/kg/day for up to 6 months ; dosages above 10 mg/kg/day should be limited to 3 months' duration, and dosages greater than 20 mg/kg/day should be avoided. Although 3-da y, intravenous therapy with etidronic acid 7.5 mg/kg/day has shown sup erior efficacy to rehydration and forced diuresis in the management of hypercalcaemia of malignancy) the efficacy of the drug is lower han t hat of the newer bisphosphonates, pamidronic acid and clodronic acid. Clinical studies involving postmenopausal w,omen with established oste oporosis have indicated that oral etidrionic acid 400 mg/day for 14 da ys as part of a 90-day cycle, repeated for lip to 3 years, increases t he bone mineral density (BMD) of the lumbar vertebrae and appears to r educe the incidence of vertebral fracture. Published data suggest that etidronic acid shows similar efficacy to hormone replacement therapy (HRT) in these respects. The above dosage also appears to be effective in preventing corticosteroid-induced osteoporosis when administered a s part of an intermittent, cyclical regimen. Etidronic acid in higher dosages (Ia to 20 mg/kg/day orally) is effective in reducing the incid ence of heterotopic ossification and its ensuing complications in both neurological and post-surgical patients. Etidronic acid is well toler ated by the majority of patients, with gastrointestinal complaints rep orted most commonly, but tends to delay the normal mineralisation of f orming bone when administered continuously at higher dosages for prolo nged periods. This is of little consequence where short term treatment is involved, but may be detrimental to those patients receiving longe r courses of therapy. This effect may be minimised or avoided by using the lowest effective dosage for as short a time as possible (as in th e above recommendations for Paget's disease), or by the use of intermi ttent cyclical therapy (as in the management of osteoporosis). Etidron ic acid therefore retains a role in tire management of resorptive bone disease, particularly in the treatment of Paget's disease, the preven tion of heterotopic ossification, and as a second-line option in postm enopausal osteoporosis. However; the development of newer bisphosphona tes requires that these compounds be continually compared and re-evalu ated.