Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy

NCT ID: NCT00485953

Last Updated: 2017-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2013-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Bone Loss; Osteoporosis; Breast Cancer

Keywords

Osteoporosis; breast cancer; aromatase inhibitors; bone loss; bone mineral density

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Active Medication Group

risedronate 35 mg weekly

Group Type: EXPERIMENTAL

risedronate

Intervention Type: DRUG

risedronate 35 mg per week

Placebo Group

Placebo

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

risedronate

risedronate 35 mg per week

Intervention Type: DRUG

Other Intervention Names

Actonel

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Susan L. Greenspan

OTHER

Sponsor Role: lead

Responsible Party

Susan L. Greenspan

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Susan L. Greenspan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Other Identifiers

PRO06080002 (REBBeCA II)

Identifier Type: -

Identifier Source: org_study_id