Clinical trial NCT00485953: Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bone Loss
Osteoporosis
Breast Cancer
Keywords: Osteoporosis
breast cancer
aromatase inhibitors
bone loss
bone mineral density
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2007-06-13
Enrollment: 109
Sex: FEMALE
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: BMD of Spine by DXA
timeFrame: at 24 months
Secondary outcomes:
measure: BMD by DXA at the Femoral Neck and Total Hip
timeFrame: at 24 months
measure: Markers of Bone Resorption and Bone Formation
timeFrame: at 24 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Susan L. Greenspan, MD
role: PRINCIPAL_INVESTIGATOR
References: