Depression, Healthy, Osteopenia, Osteoporosis
Conditions
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
Brief 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.
Interventions
DRUGAlendronate
Sponsors
National Institute of Mental Health (NIMH)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA - DEPRESSED WOMEN: The patient is a woman 21 to 45 years old on the date of the initial screening. The patient is not postmenopausal. She must be willing to practice an acceptable method of birth control, as appropriate (IUD, oral contraceptives, diaphragm, condoms, hormonal implants/injection, with the exception of subdermal levonorgestrel, sterilization) and have a negative serum pregnancy test at screening. Women currently on estrogen/progestin contraceptive therapy must have been on a stable regimen of estrogen/progestin for at least 6 months prior to enter the study. The patient understands the procedures and the risks of the study and has been informed that, alternatively, she may freely elect to be treated with the currently available treatments by her physician. The patient voluntarily agrees to participate in the study. INCLUSION CRITERIA RELATED TO THE PSYCHIATRIC STATUS: The patient had at least one episode of major depression within the last 3 years (DSM-IV). In addition, the subject has a past history (prior to the last 3 years) of at least one major depressive episode lasting more than 2 weeks. With the exception of depression, the patient is in good health, based on medical history, physical examination, and laboratory screening evaluation. The patient has a physician; either a family doctor, a psychiatrist, a psychotherapist, or another qualified health care professional who can provide medical treatment for depression. If the subject is not receiving any medical care for depression, a member of the NIH team will help the patient identify one and will work closely with this professional during the study. The patient can be on pharmacological antidepressant therapy, as medically indicated and prescribed by her primary physician or health professional. It is not a requirement of this study for subjects to stop antidepressant treatment, unless it is medically indicated for reasons such as the medication is ineffective, not well tolerated, or the patient no longer needs such treatment. This decision will be based upon their physician's evaluation. Patients starting a new antidepressant medication(s) should be on this treatment for 4-6 weeks prior to enrollment. Carbamazepine, valproic acid or thyroid hormones used as adjunctive therapy for treatment of depression are allowed. Women with a current or recent (within the past 3 years) history of alcohol or drug abuse are eligible if, in the opinion of the principal investigator, this condition is not likely to impair patient compliance or if the participation in the study does not pose additional risks to the subject. INCLUSION CRITERIA RELATED TO THE BONE STATUS: The patient has spinal anatomy suitable for dual-energy x-ray absorptiometry (DEXA) densitometry of the lumbar spine, with no evidence of vertebral fractures in at least three vertebrae. Significant scoliosis, bony trauma, osteoarthritis, and sequelae of orthopedic procedures that result in anatomy unsuitable for accurate bone densitometry, must be absent from the lumbar spine. The patient has osteopenia or osteoporosis, as indicated by a bone mineral density at the spine that is between 1.5 and 5 standard deviations below peak bone mass, or history of an osteoporotic vertebral or hip fracture. Patients whose eligibility is based only on a prevalent vertebral fracture will have the fracture confirmed by a radiologist.
Exclusion criteria
- DEPRESSED WOMEN: GENERAL
Countries
United States
Outcome results
None listed