Osteopenia, Osteoporosis
Conditions
Brief summary
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
Detailed description
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.
Interventions
alendronate sodium 70 mg tablet once week for 24 months
OTHERplacebo comparator
placebo to match alendronate sodium one tablet once a week for 24 months
Sponsors
Merck Sharp & Dohme LLC
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT | Baseline, 24 months | Trabecular number is a three-dimensional measure of the mean inter-trabecular distance; the primary micro-architectural feature measured by high-resolution CT imaging. The parameter was calculated from scans of the distal radius and distal tibia at baseline, 12, and 24 months. The percent change from baseline over these time periods was calculated as the primary outcome measure indicating the micro-architectural status of trabecular bone. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: Feb 2006-March 2007. Recruitment ads were posted at different UCSF campuses, senior centers, churches, train stations. We also utilized mass mailing lists, newspaper ad and radio broadcasts
Participants by arm
| Arm | Count |
|---|---|
| Alendronate Sodium alendronate sodium 70 mg tablet once a week for 24 months | 26 |
| Placebo placebo to match alendronate sodium | 27 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Total | Alendronate Sodium | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 26 Participants | 27 Participants |
| Age Continuous | 55.6 years STANDARD_DEVIATION 3.6 | 55.8 years STANDARD_DEVIATION 3.9 | 55.4 years STANDARD_DEVIATION 3.3 |
| Region of Enrollment United States | 53 participants | 26 participants | 27 participants |
| Sex: Female, Male Female | 53 Participants | 26 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 26 | 19 / 27 |
| serious Total, serious adverse events | 3 / 26 | 4 / 27 |
Outcome results
Primary
Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT
Trabecular number is a three-dimensional measure of the mean inter-trabecular distance; the primary micro-architectural feature measured by high-resolution CT imaging. The parameter was calculated from scans of the distal radius and distal tibia at baseline, 12, and 24 months. The percent change from baseline over these time periods was calculated as the primary outcome measure indicating the micro-architectural status of trabecular bone.
Time frame: Baseline, 24 months
Population: final statistical analysis was performed per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate Treatment | Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT | Distal Radius | 2.1 Percent change | Standard Deviation 7 |
| Alendronate Treatment | Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT | Distal Tibia | 0.9 Percent change | Standard Deviation 6.8 |
| Placebo Treatment | Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT | Distal Tibia | 4.1 Percent change | Standard Deviation 7.5 |
| Placebo Treatment | Mean % Change From Baseline in Trabecular Number (Tb.N) by HR-pQCT | Distal Radius | -0.6 Percent change | Standard Deviation 8.8 |