Etidronic acid is an orally and intravenously active
bisphosphonate, which is believed to inhibit resorption of bone via a number of cellular mechanisms, including alteration of osteoclastic activity. In studies of patients with symptomatic Paget's disease,
etidronic acid 5 to 20 mg/kg/day administered orally rapidly decreased the biochemical indices of bone turnover. Mineralisation defects in forming bone may be avoided 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-day intravenous
therapy with
etidronic acid 7.5 mg/kg/day has shown superior efficacy to
rehydration and forced diuresis in the management of hypercalcaemia of
malignancy, the efficacy of the
drug is lower than that of the newer
bisphosphonates,
pamidronic acid and
clodronic acid. Clinical studies involving postmenopausal women with established
osteoporosis have indicated that oral
etidronic acid 400 mg/day for 14 days as part of a 90-day cycle, repeated for up to 3 years, increases the bone mineral density (BMD) of the lumbar vertebrae and appears to reduce 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 as part of an intermittent, cyclical regimen.
Etidronic acid in higher dosages (10 to 20 mg/kg/day orally) is effective in reducing the incidence of
heterotopic ossification and its ensuing complications in both neurological and post-surgical patients.
Etidronic acid is well tolerated by the majority of patients, with gastrointestinal complaints reported most commonly, but tends to delay the normal mineralisation of forming bone when administered continuously at higher dosages for prolonged periods. This is of little consequence where short term treatment is involved, but may be detrimental to those patients receiving longer 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 the above recommendations for Paget's disease), or by the use of intermittent cyclical
therapy (as in the management of
osteoporosis).
Etidronic acid therefore retains a role in the management of resorptive
bone disease, particularly in the treatment of Paget's disease, the prevention of
heterotopic ossification, and as a second-line option in
postmenopausal osteoporosis. However, the development of newer
bisphosphonates requires that these compounds be continually compared and re-evaluated.