Official Title: “The Effect of Bisphosphonate on Bone Mass and Bone Turnover in Elderly, Postmenopausal Women With Breast Cancer Following Initiation of Aromatase Inhibitor Therapy”

Elderly, postmenopausal women with breast cancer on aromatase inhibitors are at increased risk of developing bone loss and osteoporosis. We postulate that in elderly, osteopenic postmenopausal women who are on aromatase inhibitor therapy, bisphosphonate therapy will (1) prevent bone loss at clinically relevant sites, such as the spine and hip and (2) decrease bone turnover.

Study Type: Interventional

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

Study Primary Completion Date: December 2010

This double-blind, placebo-controlled, randomized clinical trial will test the hypothesis that risedronate 35 mg once weekly, a potent antiresorptive agent, will prevent bone loss or improve bone mass and decrease bone turnover in elderly, osteopenic, postmenopausal women (ages 55 and older) with breast cancer on aromatase inhibitor therapy. 110 subjects will be randomized to receive either oral risedronate 35 mg once weekly or placebo for two years. Our primary outcome variable will be change in PA spine bone mineral density (BMD). Secondary endpoints will be BMD at the total hip, femoral neck, trochanter, lateral spine, forearm, and total body, and markers of bone turnover. We will also assess if the improvements in BMD are greater at sites of trabecular bone (spine) versus cortical bone (wrist). BMD will be measured at six month intervals. Biochemical markers of bone turnover will be measured at baseline, 6 months, 12 months, and 24 months.

Intervention(s) in this Clinical Trial

• Drug: risedronate
  • risedronate 35 mg per week

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • risedronate 35 mg weekly
• No Intervention: 2
  • Placebo

Primary Measures

• PA spine bone mineral density by DXA
  • Time Frame: at 6 month intervals over 2 years
    Safety Issue?: No

Secondary Measures

• BMD by DXA at the total hip, femoral neck, trochanter, lateral spine, total body, and forearm
  • Time Frame: at 6 month intervals over 2 years
    Safety Issue?: No
• Markers of bone resorption and bone formation
  • Time Frame: regular intervals over 2 years
    Safety Issue?: No

Inclusion Criteria:

• elderly postmenopausal women (ages 55 and older)
• osteopenic (DXA T-score -1.0 to -2.5 SD). However, after full counseling about the risks, benefits, and options regarding therapy for osteoporosis and discussion with her PCP, an osteoporotic woman may enroll in the study.
• with breast cancer on aromatase inhibitor therapy
• with no evidence of distant metastatic disease or osteoporosis (by BMD or clinical history)
• type of surgical procedure or addition of radiation therapy prior to this aromatase inhibitor therapy will not exclude patients
• Participants must provide voluntary, written informed consent to participate in the study, which includes understanding of the procedures, medications, and risks and benefits

Exclusion Criteria:

• Women with stage 4 breast cancer (presence of distant metastases)
• Women with normal bone density by DXA (T-score > -1.0 SD)bone density by DXA, except in the instance of a fragility fracture.
• Women with history of any illness known to affect bone and mineral metabolism, such as renal failure (estimated GFR <30), hepatic failure, malignancy (excluding breast cancer, treated superficial basal and squamous cell carcinoma and malignancies where the diagnosis itself or its treatment would not adversely affect bone metabolism), untreated primary hyperparathyroidism, and malabsorption.
• Women being treated with oral glucocorticoid therapy >3 months for suppression therapy, and certain anti-seizure medications which may adversely affect bone metabolism (phenobarbital, phenytoin, carbamazepine).
• Those with untreated active peptic ulcer disease
• Those with osteoporosis by BMD (T-score -2.5 SD at the spine or total hip) or a history of fragility fracture as an adult. However, as discussed above, osteoporotic women may elect to enroll in the study.
• Women treated with oral bisphosphonates or calcitonin for 3 months within the last year (3 month washout period)
• Men and children will be excluded because they do not get postmenopausal osteoporosis following treatment with an aromatase inhibitor
• Women with very poor dental hygiene (as assessed by the baseline dental exam) in need of dental extraction during the study
• Use of fluoride for more than 1 month ever (except for dental treatment)
• Less than 2 evaluable vertebrae
• Distant metastatic disease

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 55 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Pittsburgh

Overall Clinical Trial Officials and Contacts

Susan L. Greenspan, MD Principal Investigator University of Pittsburgh  

Overall Contact: Karen Vujevich, CRNP, MSN 412-692-2479 vujevichk@dom.pitt.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00485953

Study ID Number: PRO06080002 (REBBeCA II)

ClinicalTrials.gov Identifier: NCT00485953

Health Authority: United States: Food and Drug Administration