Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group

N Engl J Med. 1995 Nov 30;333(22):1437-43. doi: 10.1056/NEJM199511303332201.


Background: Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed.

Methods: We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements.

Results: The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons). The 5-mg dose was less effective than the 10-mg dose, and the regimen of 20 mg followed by 5 mg was similar in efficacy to the 10-mg dose. Overall, treatment with alendronate was associated with a 48 percent reduction in the proportion of women with new vertebral fractures (3.2 percent, vs. 6.2 percent in the placebo group; P = 0.03), a decreased progression of vertebral deformities (33 percent, vs. 41 percent in the placebo group; P = 0.028), and a reduced loss of height (P = 0.005) and was well tolerated.

Conclusions: Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alendronate
  • Body Height / drug effects
  • Bone Density / drug effects*
  • Calcium Carbonate / therapeutic use
  • Diphosphonates / adverse effects
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use*
  • Double-Blind Method
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology
  • Fractures, Bone / prevention & control*
  • Humans
  • Incidence
  • Middle Aged
  • Osteoporosis, Postmenopausal / complications
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Spinal Fractures / epidemiology
  • Spinal Fractures / etiology
  • Spinal Fractures / prevention & control
  • Spine / drug effects


  • Diphosphonates
  • Calcium Carbonate
  • Alendronate