CAN BISPHOSPHONATES REDUCE THE RISK OF FRACTURE IN OSTEOPOROSIS?

Kay Lowney, MD
8/2/96

CASE SCENARIO:

A 52-year-old thin white female with a strong family history of breast cancer presents to your clinic for a routine visit. She is perimenopausal and not interested in hormone therapy because she is afraid of breast cancer. She has heard about a new treatment for osteoporosis and wonders if she should be taking it.

CLINICAL BOTTOM LINES:

1) Estrogen is the only approved preventive medical therapy for post-menopausal osteoporosis.

2) Estrogen is the most effective therapy of established OP, reducing fracture rates by about 50%.

3) Newer bisphosphonates (like alendronate) are effective in increasing bone density and reducing
fracture rates in women with established OP.

4) Bisphosphonates have not yet been studied in early menopausal women for the prevention of
osteoporosis. They are well-tolerated and have not shown significant adverse effects when used for long periods in other bone diseases.

THE EVIDENCE:

A RCT of 994 women with post-menopausal OP treated with alendronate vs. placebo were followed for 3 years, monitoring bone mineral density and fracture rates.

COMMENTS:

1) Vertebral fractures are more common and occur earlier in the disease process than non-vertebral fractures. A longer study may have shown a more dramatic reduction in non-vertebral fractures.

2) Alendronate was also associated with significant, progressive increases in bone densities at all skeletal sites (distal forearm, head of femur, vertebrae). Placebo-treated patients had uniformly decreased bone densities. Bone densities are widely accepted as an accurate predictor of risk for new fractures.

3) The lowest effective dose of alendronate is 10 mg daily. Higher doses were no more effective.Discontinuation of the drug resulted in significant reduction in bone density, suggesting that there is no residual benefit once the drug is stopped.

4) All women in the study were also treated with calcium, 600 mg daily. Calcium supplements slow the progression of bone loss in older women with calcium-deficient diets, but do not significantly reduce fracture rates if the diet is not deficient.

5) Questions not answered: Does alendronate preserve bone density in women who do not already have significant osteoporosis? Is there any added benefit to hormone replacement and alendronate in either the prevention or treatment of osteoporosis? Are there adverse effects of alendronate when taken for extended periods - 20 years or more?

6) Bone mineral density studies are becoming less expensive and easier to obtain. In the near future it may be cost-effective to screen perimenopausal women to identify those that would most benefit from preventive therapy.

Reference: Liberman et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in post-menopausal osteoporosis. NEJM 1995; 33:1437-1443.