Bone Loss, Breast Cancer, Osteoporosis
Conditions
Keywords
Osteoporosis, breast cancer, aromatase inhibitors, bone loss, bone mineral density
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.
Interventions
DRUGrisedronate
risedronate 35 mg per week
Sponsors
University of Pittsburgh
Susan L. Greenspan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to No maximum
Healthy volunteers
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BMD of Spine by DXA | at 24 months | BMD is the bone mineral density of the lumbar spine measured using the dual-energy x-ray absorptometry (DXA) scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMD by DXA at the Femoral Neck and Total Hip | 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. |
| Markers of Bone Resorption and Bone Formation | at 24 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Medicine Group risedronate 35 mg weekly | 55 |
| Placebo Group Received placebo medication once per week | 54 |
| Total | 109 |
Baseline characteristics
| Characteristic | Active Medicine Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 20 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 34 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 53 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 53 Participants | 100 Participants |
| Region of Enrollment United States | 55 participants | 54 participants | 109 participants |
| Sex: Female, Male Female | 55 Participants | 54 Participants | 109 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 | 52 / 55 | 50 / 54 |
| serious Total, serious adverse events | 10 / 55 | 16 / 54 |
Outcome results
Primary
BMD of Spine by DXA
BMD is the bone mineral density of the lumbar spine measured using the dual-energy x-ray absorptometry (DXA) scan.
Time frame: at 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Medicine Group | BMD of Spine by DXA | 2.269 percentage change | Standard Error 0.583 |
| Placebo Group | BMD of Spine by DXA | -1.735 percentage change | Standard Error 0.611 |
Secondary
BMD by DXA at the Femoral Neck and Total Hip
BMD is the bone mineral density of the femoral neck and total hip measured using the dual-energy x-ray absorptiometry (DXA) scan.
Time frame: at 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Medicine Group | BMD by DXA at the Femoral Neck and Total Hip | Total Hip BMD | 0.558 percentage change | Standard Error 0.37 |
| Active Medicine Group | BMD by DXA at the Femoral Neck and Total Hip | Femoral Neck BMD | 0.408 percentage change | Standard Error 0.607 |
| Placebo Group | BMD by DXA at the Femoral Neck and Total Hip | Total Hip BMD | -2.748 percentage change | Standard Error 0.487 |
| Placebo Group | BMD by DXA at the Femoral Neck and Total Hip | Femoral Neck BMD | -2.137 percentage change | Standard Error 0.628 |
Secondary
Markers of Bone Resorption and Bone Formation
Time frame: at 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Medicine Group | Markers of Bone Resorption and Bone Formation | CTX | -14.906 percentage change | Standard Error 10.317 |
| Active Medicine Group | Markers of Bone Resorption and Bone Formation | P1NP | -46.863 percentage change | Standard Error 3.025 |
| Placebo Group | Markers of Bone Resorption and Bone Formation | CTX | -4.077 percentage change | Standard Error 8.179 |
| Placebo Group | Markers of Bone Resorption and Bone Formation | P1NP | -1.630 percentage change | Standard Error 5.732 |