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

• ClinicalTrials.gov Identifier: NCT00485953
• Recruitment Status: Completed
• First Posted: June 13, 2007
• Results First Posted: July 3, 2014
• Last Update Posted: October 13, 2017
• Sponsor: Susan L. Greenspan
• Collaborator: University of Pittsburgh
• Information provided by (Responsible Party): Susan L. Greenspan, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bone Loss; Osteoporosis; Breast Cancer	Drug: risedronate	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• 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
• Study Start Date: September 2007
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Medication Group; risedronate 35 mg weekly	Drug: risedronate; risedronate 35 mg per week; Other Name: Actonel
No Intervention: Placebo Group; Placebo

Outcome Measures

Primary Outcome Measures :

1. BMD of Spine by DXA [ Time Frame: at 24 months ]
   BMD is the bone mineral density of the lumbar spine measured using the dual-energy x-ray absorptometry (DXA) scan.

Secondary Outcome Measures :

1. BMD by DXA at the Femoral Neck and Total Hip [ Time Frame: at 24 months ]
   BMD is the bone mineral density of the femoral neck and total hip measured using the dual-energy x-ray absorptiometry (DXA) scan.
2. Markers of Bone Resorption and Bone Formation [ Time Frame: at 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 55 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Susan L. Greenspan

University of Pittsburgh

Investigators

• Principal Investigator: Susan L. Greenspan, MD; University of Pittsburgh

More Information

• Responsible Party: Susan L. Greenspan, Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00485953
• Other Study ID Numbers: PRO06080002 (REBBeCA II)
• First Posted: June 13, 2007
• Results First Posted: July 3, 2014
• Last Update Posted: October 13, 2017
• Last Verified: September 2017

Keywords provided by Susan L. Greenspan, University of Pittsburgh:

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

Additional relevant MeSH terms:

Breast Neoplasms; Osteoporosis; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Risedronic Acid; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents