Long-term Alendronate Therapy Demonstrated Sustained Therapeutic Effects in Osteoporotic Postmenopausal Women

Introduction

Alendronate is a potent inhibitor of bone resorption. It has produced sustained reductions in biochemical markers of bone remodelling into the premenopausal range and consistent dose-related increases in bone mineral density in a variety of populations, including elderly women.

Aim

To investigate the effects of prolonged alendronate therapy as well as its discontinuation in postmenopausal women with osteoporosis.

Patient Profile

Postmenopausal women with osteoporosis that had been diagnosed on the basis of the bone mineral density of the lumbar spine.

Methods

Study Design

• Multicentre, randomized, double-blind, placebo-controlled, phase 3
• 17 sites in the United States and 12 in other countries
• N=994
• Women were randomly assigned to receive 5, 10, or 20 mg of oral alendronate or placebo daily
• Women in 20-mg group received 5 mg for years 3 through 5 and placebo for years 6 through 10  (discontinuation group)
• Duration:  10 years

Endpoints

Primary endpoint

• The change in bone mineral density at the lumbar spine

Secondary endpoints

• Changes in bone mineral density at the femoral neck, trochanter, total proximal femur (“total hip”), total body, and forearm regions; changes in the levels of urinary N-telopeptides of type I collagen, a biochemical marker of bone resorption
• Changes in the levels of serum bone-specific alkaline phosphatase and total serum alkaline phosphatase, indicators of the rates of bone formation

Results

• The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling
  • Significant decreases occurred at the total hip, femoral neck, and forearm, but bone mineral density at the lumbar spine, trochanter, total hip, and total body remained significantly above baseline values at year 10
• The safety profiles were similar among all three groups
  • Prolonged treatment did not result in any loss of benefit
  • Alendronate associated deaths were absent

Conclusion

• Alendronate 10 mg daily for 10 years was associated with sustained therapeutic effects on bone density and remodelling
• There was no indication that the antifracture efficacy of the drug was diminished
• Gradual reduction of effect was observed after discontinuation of alendronate

N Engl J Med. 2004; 350(12):1189-99