Official Title: “Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal”

The purpose of this study is to evaluate the changes in bone structure as determined by magnetic resonance imaging measurements among early postmenopausal women after 24 months of treatment with alendronate, 70 mg once a week as compared to placebo

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: February 2009

This is a randomized, double-blind, 24-month study. Fifty-five postmenopausal women, age range of 45-65 years, with low bone density will be recruited, with half of the subjects receiving alendronate + 2800 IU of vitamin D once weekly, the other half receiving placebo + 2800 IU of vitamin D once weekly. All study subjects will receive supplemental calcium 1000 mg/day + Vitamin D 400 IU/day. Measurements of microarchitecture will be made in the wrist, ankle, and hip, and the changes in trabecular bone will be assessed at 0, 12 and 24 months.

Markers of bone turnover and bone mineral density (BMD) will be used to characterize the cohort and postmenopausal changes in bone turnover and density.

Intervention(s) in this Clinical Trial

• Drug: alendronate
  • 70 mg once a week for 2 years

Primary Measures

• Mean percent change from baseline in apparent trabecular number at the distal radius at 24 months of treatment with alendronate, 70 mg once a week as compared to placebo.
  • Time Frame: 24 months
    Safety Issue?: Yes

Inclusion Criteria:

• early postmenopausal women
• 45-65 years old
• T-score range -1.1 to -2.5 either at the lumbar spine or any hip site exclusive of Ward's triangle
• at least 3 vertebrae rom L1-L4 must be evaluable

Exclusion Criteria:

• Those at high risk for osteoporotic fracture within the next 24 months, such that randomization to a placebo would be unacceptable (e.g., prior history of hip fracture, recent symptomatic clinical vertebral fracture, or very low BMD [i.e., BMD > 2.5 SD below young normal bone mass at any site exclusive of Ward's Triangle])
• Current excessive tobacco use
• Abnormality of the esophagus which delays esophageal emptying, such as stricture or achalasia
• Gastroesophageal reflux disease sufficient to require regular medication
• Inability to stand or sit upright for at least 30 minutes once a week
• Current use of any illicit drugs or has a history of drug or alcohol abuse within the past 5 years
• Current alcohol use > 3 drinks/day
• Any of the following: hypocalcemia; severe malabsorption syndrome; moderate or severe hypertension which is uncontrolled; new onset angina or myocardial infarction within six months of entry into the study; evidence for impaired renal function defined as creatinine clearance <35 ml/min or serum creatinine greater than 1.6 mg/dL; organ transplantation; or other significant end organ diseases (genitourinary, cardiovascular, endocrine, hepatic, psychiatric, renal, hematologic, or pulmonary) which, in the opinion of the investigator, may pose an added risk to the patient or impair the patient's ability to complete the trial
• History of or evidence for metabolic bone disease (other than postmenopausal bone loss) including but not limited to vitamin D deficiency (25-hydroxy-vitamin D level
• <10 ng/ml), hypoparathyroidism, recent hyperthyroidism (suppressed TSH within the six months prior to entry into the study), Paget's disease of bone, Cushing's disease, osteomalacia and renal osteodystrophy
• History of cancer. However, patients with the following cancers will be considered eligible for the study: 1) superficial basal or squamous cell carcinoma of the skin which has been completely resected; 2) other malignancies completely treated without recurrence or treatment in the last 5 years, with the following exceptions: patients with a history of breast cancer (including histologic diagnosis of lobular carcinoma in situ), endometrial carcinoma, or other known or suspected estrogen-sensitive neoplasia are excluded regardless of time since treatment or disease status
• Any treatment with a bisphosphonate or parathyroid hormone; within the last 6 months: estrogen, estrogen analogues (e.g. raloxifene, tamoxifen) tibolone or anabolic steroids; Estrogen taken > 3 months ago for < 1 week is acceptable; Topical (vaginal) estrogen cream (< 2 g) used up to 2 times weekly is acceptable; Thyroid hormone, unless on a stable dose for at least six weeks before randomization with serum TSH within normal range; Fluoride treatment at a dose greater than 1 mg/day for more than 1 month at any time; given for a shorter time than one month it must have been greater than 1 year before randomization; Glucocorticoid treatment for more than one month with > 7.5 mg of oral prednisone (or the equivalent) per day within six months prior to randomization; patients who have received therapeutic glucocorticoids in the past must be considered highly unlikely to require retreatment with any dose of oral glucocorticoids for more than one month during the course of the study; Treatment with an immunosuppressant (e.g., cyclosporine, azathioprine) within the previous year.
• Current or expected treatment during the course of the study of any medication which might alter bone or calcium metabolism, including vitamin A in excess of 10,000 IU per day, or vitamin D in excess of 5,000IU per day, calcitonin, phenytoin, heparin, or lithium.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Thomas M Link, MD Principal Investigator University of California, San Francisco  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00504166

Study ID Number: M250

ClinicalTrials.gov Identifier: NCT00504166

Health Authority: United States: Food and Drug Administration