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

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.

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