Am Fam Physician. 1999 Nov 15;60(8):2428.
Hip and spine fractures are serious complications of osteoporosis. After menopause, bone mineral density (BMD) rapidly declines. The use of the antiresorptive agent, alendronate, has been shown to maintain and improve BMD in postmenopausal women. To date, it has been presumed, but not proved, that BMD increase is associated with a decreased risk of vertebral fractures. Hochberg and colleagues evaluated this hypothesis by using data from the Fracture Intervention Trial Research Group.
Women between the ages of 55 and 81 years were included in the study. They were at least two years postmenopause and had a BMD of 1.6 standard deviation or more below the mean. Exclusion criteria included a history of erosive upper gastrointestinal disease, abnormal renal function, hypertension or myocardial infarction in the previous six months. Other exclusion criteria were the use of fluoride or bisphosphonates at any time in the past or the use of estrogen or calcitonin in the previous six months. The daily dosage of alendronate was 5 mg for the first 24 months. This was increased to 10 mg per day after other studies showed a greater increase in BMD with the higher dose and no increase in side effects. Women whose daily calcium intake was less than 1,000 mg received a daily supplement of 500 mg of calcium and 250 IU of vitamin D.
BMD studies of the lumbar spine, femoral neck and total hip were done at baseline and yearly thereafter. The women were followed for 2.9 to 4.5 years, depending on baseline fracture history. Lateral spine radiographs were done at baseline and periodically during the follow-up period. A new vertebral fracture was considered to be a decrease of at least 20 percent and 4 mm in the height of any vertebrae, relative to baseline. Changes in BMD were classified as no gain, less than 3 percent, or 3 percent and more.
Data were analyzed on 2,984 women. The mean age was 68.6 ± 6.1 years and the mean number of years since menopause was 22.2 ± 8.5. Increases in BMD were noted in 70 to 89 percent of women at 12 months and in 76 to 91 percent at 24 months. The degree of increase depended on the site of measurement. The women with the greatest increases—3 percent or more—in BMD had the lowest incidence of new vertebral fractures. During the nearly four years of follow-up, the cumulative incidence of new fractures was 3.2 percent during the first 12 months of alendronate therapy, compared with 6.3 percent for women who had a decline or no change in BMD. A similar pattern was observed at 24 months.
The authors conclude from their data that the use of alendronate produces the greatest increase in BMD during months 12 to 24 after starting treatment. There is a direct relationship between the increase in BMD and a decrease in new vertebral fractures. Those patients who have at least a 3 percent increase in BMD achieve the most benefit.
Hochberg MC. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis Rheum. June 1999;42:1246–54.
Copyright © 1999 by the American Academy of Family Physicians.
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