The biphosphonates remain the drugs of choice for treatment. Etidronate is usually given daily for two weeks every three months. Aledronate and risedronate are currently approved for daily use. Both alendronate and risedronate can prevent bone loss when given to women in the perimenopausal period. Daily administration of biphosponates can cause esophageal irritation which precludes their use in a significant number of patients.
Weekly doses avoid esophageal irritation in canine models.
Studies on weekly alendronate therapy to humans are underway. They work by suppressing osteoclast-activating enzymes, by antagonizing parathyroid induced bone resorption, and by increasing gut absorption and reducing renal loss of calcium. Estrogens plus biphosphonates have additive effects on BMD and this combination should probably be tried in women who fail to adequately respond to single drug therapy. It is hoped that these agents will retain estrogen's beneficial effect on bone and lipids, have much less neoplastic effect on breast and endometrial tissue and decrease the incidence of hot flashes and thromboembolism. Raloxifne is the first of these compounds to be released but unfortunately it has limited effects on hot flashes and is associated with an increased incidence of thromboembolism similar to that seen with estrogen therapy.