The P.O.W.E.R. STUDY (Premenopause, Osteopenia/Osteoporosis, Women, Alendronate, Depression)

This is a five-year study on the natural history of bone turn-over in depressed premenopausal women, ages 21 to 45 years, with normal bone mass, and the response to treatment with alendronate in depressed premenopausal women, ages 21 to 45 with low bone mass (as indicated by a bone mineral density (BMD) of negative 1.5 SD below peak bone mass at the spine and/or hip). Osteopenia is defined as a BMD at the spine and/or hip that is between negative 1.5 and negative 2.5 SD; osteoporosis is defined as a BMD that is below negative 2.5 SD at the spine and/or hip. During the initial screening, the women are evaluated for depression. Women who meet DSM-IV diagnostic criteria for Major Depressive Disorder as indicated by a structured psychiatric interview (SCID-IV and HAM-D), will then undergo a DEXA scan to determine BMD. Participants will be divided into four subcategories based on BMD results. Premenopausal depressed women with normal BMD (less than negative 1 SD below the average peak bone mass at the spine and/or hip) (Group B) will be matched by age, race, and body mass index to a control group of healthy, premenopausal, non-depressed women with normal bone mass (Group A). Groups A and B will be followed for 12 months with DEXA determinations every 6 months, measurements of bone turnover markers every 3 months, measurements of relevant endocrine parameters every 3 months, an exercise substudy at 0, 6, and 12 months, and collection of a DNA sample at one of the above visits.

Women with depression and low BMD (negative 1.5 SD below peak bone mass at the spine and/or hip) will enter a 12-month, placebo-controlled, clinical trial where they will be randomized either to blind alendronate 70 mg once a week (Group C) or blind placebo once a week (Group D). In addition to alendronate 70 mg once a week or placebo once a week, women in Groups C and D will also receive daily 500 mg of elemental calcium and 400 IU of vitamin D. DEXA determinations will be performed at Screening, Month 0, Month 6, and Month 12. Determination of biochemical markers of bone turnover and endocrine parameters relevant to depression will be performed at 0, 3, 6, 9 and 12 months. An exercise substudy will be performed at 0, 6, and 12 months. The collection of a DNA sample will also be performed at one of the above visits.