Alendronate Prevents Postmenopausal Bone Loss in Women without Osteoporosis: A Double-Blind, Randomized, Controlled Trial

Abstract

In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

“…The finding of normal osteoid thickness and a decreased mineralizing surface (the length of double-tetracyclinelabeled cancellous bone plus half the length of single-tetracycline-labeled cancellous bone) in the alendronate groups as compared with the placebo group has already been reported. 3 To our knowledge, the rates of bone formation and mineral apposition and the number of osteoclasts have not been previously reported.…”

“…3 The trial by McClung et al was a prevention trial, and the bone mineral density of the patients was within 2 SD above or below normal peak adult values at the initiation of the trial. However, the bone mineral density of the patients at baseline was approximately 10% below the mean value for young adult women, and the bone mineral density in patients receiving placebo decreased by 3 to 4% at the spine, femoral neck, and trochanter during the trial.…”

“…This result indicates that these women were having postmenopausal bone loss. 3 Women who had disorders of bone and mineral metabolism, smoked more than 20 cigarettes per day, or consumed three or more alcoholic drinks per day were excluded. The patients were randomly assigned to one of five groups: those receiving placebo for 3 years; oral alendronate at a dose of 1, 5, or 10 mg per day for 3 years; or oral alendronate at a dose of 20 mg per day for 2 years, followed by placebo for 1 year.…”

“…Alendronate also decreased the levels of biochemical markers of bone turnover as compared with baseline. [1][2][3] After 3 years of treatment, 55 patients volunteered to undergo a transiliac bone biopsy to determine whether the drug had impaired skeletal mineralization, as had occurred with etidronate, a first-generation bisphosphonate. 17 To label the bone for the measurement of the mineral appositional rate and the mineralizing perimeter, the patients were given oral tetracycline hydrochloride (250 mg four times per day) 19, 18, 7, and 6 days before the biopsy.…”

“…To reconcile the paradoxical findings of these studies, we conducted an in-depth examination of osteoclast morphologic features in bonebiopsy specimens from women who had participated in a trial of alendronate for the prevention of postmenopausal osteoporosis. 3 …”