Bone Loss in Premenopausal Women With Depression
Condition: Depression; Healthy; Osteopenia; Osteoporosis
MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether women with major depression lose bone mass
      at a faster rate than women without depression. This study will also determine if the drug
      alendronate can maintain or increase bone mass in premenopausal women with major depression
      and osteoporosis.

      Depression may be a major risk factor for osteoporosis; it is associated with abnormally
      elevated stress hormone levels that may contribute to bone loss. This study will evaluate
      bone mass in women with depression and healthy volunteers.

      Participants will undergo psychiatric, medical, dietary, and stress hormone evaluations and
      bone mineral density (BMD) measurements.

      Participants with depression will be divided into two groups: those with normal BMD and those
      with low BMD. Depressed participants with normal BMD will be compared to a control group of
      healthy premenopausal women with normal BMD and followed for 36 months. Dual energy X-ray
      absorptiometry (DEXA) determinations will be made at months 6, 12, 24 and 36; bone turnover
      and endocrine parameters of depression will be

      measured every 3 to 6 months.

      Participants with depression and low BMD will be randomly assigned to receive either
      alendronate or placebo (an inactive pill) once a week for 24 months. Participants will
      receive calcium and vitamin D supplements daily. DEXA determinations will be performed at
      screening, and at Months 6, 12, 18 and 24; bone turnover and endocrine parameters of
      depression will be measured every 3 to 6 months.

      For both groups, up to four of the visits may optimally be done as inpatient stays of two
      nights. All remaining visits are as outpatients.
    

Detailed description: 
      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.
    

Intervention name(s): Alendronate
Intervention type(s): Drug
Intervention MeSH terms: Alendronate
Primary purpose: Treatment
Keywords: Preventive Medicine; Women's Health; Bone Formation; Mood Disorders; Bone Resorption; Major Depression; Osteopenia; Osteoporosis; Bone Fracture; Bisphosphonate; Depression; Bone Density; Healthy Volunteer; HV; Normal Control