Patient description: The patient is a 47-year-old Asian woman complaining of persistent feelings of sadness. She lost interest in activities she used to enjoy. She states that her mood is mostly depressed for the past 3 weeks. She also lost her appetite , which led to about 5kg weight loss. She complains of loss of energy and feelings of worthlessness nearly every day. She is not using any drugs and she does not smoke. She doesn't drink alcohol. She used to exercise every day for at least 30 min. But she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was recently diagnosed with colon cancer and he is starting his chemotherapy. There is nothing remarkable in her past medical history and her drug history is only positive for Vit D3 1000 units daily. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 21.0-45.0,  Depression Healthy Osteopenia Osteoporosis 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. TO THE 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. TO THE BONE 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 is based only on a prevalent vertebral fracture will have the fracture confirmed by a radiologist  WOMEN The patient is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained. Pregnancy or breast-feeding. Menopause. The patient plans to move within the next 12 months to a location which could impair a continued follow-up. The patient has a history of or evidence for an illness or has significant abnormalities on prestudy clinical or laboratory evaluations, which, in the opinion of the principal investigator, might complicate the interpretation of the data or pose additional risk to the subject. The patient has any of the following medical conditions: any malabsorption syndrome, significant genitourinary, renal (serum creatinine greater than or equal to 1.6 mg/dL), hepatic, or pulmonary disease; uncontrolled hypertension; uncontrolled diabetes mellitus; decompensated heart failure; clinically significant arrhythmias; unstable angina, any immunodeficiency syndrome including AIDS. The patient has received any drug of investigation within 30 days of the start of the study. The use of subdermal levonorgestrel and similar preparations TO THE The patient does not have an outside care provider for treatment of depression. The patient is judged to be at suicidal risk, as clinically evident or indicated by a score of 4 at the Hamilton Scale, question 3 (suicide), or by reports of suicidal intent during SCID-IV interview. The patient has a history suggesting potential for self-harm or violence towards others. The patient currently has psychotic depression (e.g. hallucinations, delusions). The patient has schizoaffective disorder. Patients with a diagnosis of active anorexia nervosa, bulimia or any other eating disorder are not eligible. Patients with a diagnosis of bipolar disorders type 1 or type 2 or any psychotic disorder other than psychotic depression are not eligible. Women with a current or recent (within the past 3 years) history of alcohol or drug dependence are not eligible TO THE BONE OR THE USE OF The patient is affected by severe osteoporosis, as indicated by a history of recurrent non-traumatic fractures and/or a BMD value which is below 4 SD the peak bone mass at the spine and/or the hip. The patient has a history of recent major upper gastrointestinal (GI) (esophagus, stomach, duodenum) mucosal erosive disease. As defined by (1) significant upper GI bleeding within the last year resulting in hospitalization and/or transfusion. (2) Recurrent ulcer disease documented by radiographic or endoscopic means (two episodes in the last two years, or any documented ulcer in the preceeding 3 months). (3) Uncontrolled dyspepsia currently treated on a daily basis. (4) Esophageal or gastric variceal disease or (5) esophageal stricture, achalasia, or severe esophageal motor dysfunction. (This only applies to Group C and D) The patient has a history of cancer with the following exceptions: (1) superficial basal or squamous cell carcinoma of the skin that was treated, and (2) other malignancies treated at least 10 years ago without any evidence of recurrence. The patient has a history of, or evidence for, metabolic bone disease (other than low bone mineral density) including, but not limited to uncontrolled hyper or hypocalcemia, hyper- or hypoparathyroidism, Paget's disease of bone, osteomalacia, or osteogenesis imperfecta. Patients with surgically cured hyperparathyrodism due to parathyroid adenoma (at least one year prior to randomization) are eligible for in the trial. Patients with well-controlled hyper or hypothyrodism, as indicated by clinical evaluation and normal plasma TSH level are eligible for in the trial. The patient has received treatment prior to enrollment in the study that might have influenced bone turnover including: Beginning a regimen (for more than 2 consecutive weeks) within the last 6 months, of any estrogen preparation including mixed estrogen agonist/antagonist, (e.g., tamoxifen or raloxifene) or progestins. Having used within the last 6 months any of the following: anabolic steroids (including DHEA and other weaker analogs), calcitonin, calcitriol, alfacalcidol, excess vitamin A (greater than 10,000 units/day) or vitamin D (greater than 1,000 units/day), cyclosporine, or anticonvulsivants. The patient is on a thyroid hormone for treatment of a thyroid condition, unless the patient has received a stable dose for the last 6 weeks prior to study enrollment, and is euthyroid, as documented by an ultrasensitive TSH serum assay. The patient is on fluoride at a dose greater than 1 mg/day any time (fluoride taken greater than 3 months ago for less than 1 week is acceptable). The patient has a history of glucocorticoid treatment for more than 1 month, within 6 months prior to study start (patients who received therapeutic glucocorticoids in the past must be considered unlikely to need glucocorticoid treatment during the course of the study). Any previous treatment with bisphophonates for more than 2 weeks. The patient's screening 25-hydroxyvitamin D level is less than 15 ng/mL unless 24-h urine calcium and serum PTH, calcium, and alkaline phosphatase are all within the normal range. The patient is not able to stand or sit upright for at least 30 minutes. The patient has a body weight greater than 137 kg, due to limitations in the accuracy of DEXA measurements above this body weight TO THE (COOPER) TEST: Subjects on beta-blockers will not be eligible to participate in the 12-min test WOMEN: Healthy control women must be of good physical health; specifically, no history of any DSM-IV diagnoses, including but not limited to depression and anorexia nervosa. They also must have normal bone density, no history of osteoporotic fractures, and be willing to be on a valid contraceptive method WOMEN: Control women should not have any of the risk factors for bone loss such as smoking, alcohol abuse, dietary imbalances unless the risk factor is present only to a mild extent