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
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.