Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Alendronate reduced new vertebral fractures in postmenopausal osteoporosis

ACP J Club. 1996 Mar-April;124:33. doi:10.7326/ACPJC-1996-124-2-033


Source Citation

Liberman UA, Weiss SR, Bröll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med. 1995 Nov 30; 333:1437-43.


Abstract

Objective

To determine whether oral alendronate increases bone mineral density and decreases the incidence of vertebral fractures and loss of height in postmenopausal women with osteoporosis.

Design

Randomized, double-blind, placebo-controlled trial with 3-year follow-up.

Setting

Clinics in North and South America, Europe, Asia, and Australia.

Patients

994 women who were ≥ 5 years from menopause, were aged 45 to 80 years (mean age 64 y), and had confirmed osteoporosis. Exclusion criteria were secondary causes of osteoporosis; active peptic ulcer disease; renal or hepatic impairment; abnormalities of the lumbar spine that precluded bone mineral density assessment; history of hip fractures; and treatment with bisphosphonates, hormones, calcitonin, fluoride, or anabolic steroids. 91% of women completed ≥ 1 year of treatment.

Intervention

All women received calcium, 500 mg/d. For 2 years, 40% of women received placebo; 20% received alendronate, 5 mg; 20% received alendronate, 10 mg; and 20% received alendronate, 20 mg/d. For the third year, women who received alendronate, 20 mg, were switched to alendronate, 5 mg.

Main Outcome Measures

Bone mineral density of the lumbar spine, femoral neck, trochanter, forearm, and total body measured by dual energy x-ray absorptiometry; vertebral fractures and deformity detected by spinal films; and height.

Main Results

Analysis was by intention to treat; placebo data were compared with data from the women who received all alendronate doses combined. Women in all 3 alendronate groups had significant increases in bone mineral density compared with women in the placebo group, who had significant decreases in bone mineral density. Overall, women who received alendronate had fewer new vertebral fractures (3% vs 6%, P < 0.03). {This absolute risk reduction of 3% means that 34 women with osteoporosis would have to be treated to prevent 1 new fracture over 3 years, 95% CI 16 to 518; the relative risk reduction was 48%, CI 4% to 72%.}* Women who received alendronate had fewer increases in the spine deformity index (33% vs 41%, P = 0.03) and had a lower mean loss of height (3.0 vs 4.6 mm, P = 0.005). The groups did not differ for nonvertebral fractures, adverse effects, or rates of discontinuation of treatment.

Conclusion

In postmenopausal women with osteoporosis, alendronate increased bone mineral density and decreased the incidence of new vertebral fractures.

Source of funding: Merck Research Laboratories.

For article reprint: Dr. U.A. Liberman, Metabolic Diseases, Beilinson Medical Center, 49100, Petah-Tikva, Israel. FAX 972-3-937-6143.

*Numbers calculated from data in article.


Commentary

Osteoporosis is a major public health problem. Optimal prevention aims at maximizing peak bone mass in early adulthood and minimizing postmenopausal bone loss. Alendronate, which is an aminobisphosphonate, potently inhibits osteoclastic bone resorption. Liberman and colleagues found that 3 years of alendronate therapy in postmenopausal women with osteoporosis increased bone density of the spine, hip, and total body and decreased vertebral deformities and loss of height. Despite these positive results, several issues should be considered before alendronate is widely prescribed.

First, bisphosphonates accumulate in the skeleton; the effect of long-term alendronate on bone turnover and strength is unknown (1). Second, most published therapeutic trials in women with osteoporosis enrolled women with ≥ 1 vertebral fracture at baseline. Because this study used the arbitrary World Health Organization (WHO) definition of osteoporosis (reduction in bone mineral density of ≥ 2.5 SD below the mean value for premenopausal white women [2]), women without vertebral fractures at baseline were also studied. Unfortunately, bone mass accounts for only 70% to 80% of bone strength (3); age, previous fracture, and fast rates of bone loss also contribute to fracture risk. Treatment thresholds should be based on an individual patient's risk for fracture. Until we have a definition of osteoporosis that incorporates both bone mineral density and other risk factors, it is premature to use the WHO criteria in clinical practice.

Finally, the effectiveness of alendronate as a therapy for postmenopausal women with established osteoporosis should not be used to infer that alendronate would also prevent bone loss from estrogen deficiency. Future studies to see whether alendronate prevents osteoporosis in women in early menopause are anticipated.

Nancy Lane, MD
University of CaliforniaSan Francisco, California, USA


References

1. Sambrook PN. The treatment of postmenopausal osteoporosis. N Engl J Med. 1995;333:1495-6.

2. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. Diagnosis of osteoporosis. J Bone Min Res. 1994;9:1137-41.

3. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet. 1993;341:72-5.