Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group.

CONTEXT: The principle of "regression to the mean" predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change.

OBJECTIVE

To test whether women who lose bone mineral density (BMD) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year.

DESIGN AND

SETTING

Two randomized, double-blind, placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial.

PARTICIPANTS AND INTERVENTIONS: Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication (n = 2634), and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication (n = 3954).

MAIN OUTCOME MEASURES: Baseline, 12-, and 24-month hip and spine BMD.

RESULTS

Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment. Specifically, among women taking alendronate whose hip BMD decreased by more than 4% during the first year, 83% (95% confidence interval [CI], 82%-84%)had increases in hip BMD during the second year, with an overall mean increase of 4.7%. In contrast, those who seemed to gain at least 8% during the first year lost an average of 1% (95% CI, 0.1%-1.9%) during the next year. Similar results were observed among women taking raloxifene for 2 years.

CONCLUSIONS

Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year. These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use.