Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial.

UNLABELLED: In postmenopausal women with low bone mass and hormone-receptor-positive breast cancer on an aromatase inhibitor, risedronate maintained skeletal health assessed by bone density and turnover markers. Women with the greatest decreases in bone turnover markers at 12 months had the greatest increases in bone density at 24 months. INTRODUCTION: Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone-receptor-positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if (1) oral bisphosphonate therapy can prevent bone loss in women on an AI and (2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). METHODS: We conducted a 2-year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an AI (anastrozole, letrozole, or exemestane) for hormone-receptor-positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo, and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)], and safety. RESULTS: Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p < 0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 µg/mL for P1NP (both p < 0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p < 0.05). The oral therapy was safe and well tolerated. CONCLUSION: In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health.

The effect of risedronate on hip structural geometry in chemotherapy-induced postmenopausal women with or without use of aromatase inhibitors: a 2-year trial.

INTRODUCTION: Osteoporosis is a major health problem for postmenopausal women. Adjuvant hormonal therapy with aromatase inhibitors (AIs) in postmenopausal breast cancer patients further worsens bone loss. Bisphosphonates are able to prevent AI-induced bone loss, but limited data exists on their effect on bone structure. Our objectives were to (1) examine the impact of AIs and no-AIs on hip structural geometry (HSA) of chemotherapy-induced postmenopausal women, and (2) determine if oral bisphosphonates could affect these changes. METHODS: This is a sub-analysis of a 2-year double-blind randomized trial of 67 women with nonmetastatic breast cancer, newly postmenopausal following chemotherapy (up to 8 years), who were randomized to risedronate, 35 mg once weekly (RIS) and placebo (PBO). Many women changed their cancer therapy from a no-AI to an AI during the trial. Outcomes were changes in Beck's HSA-derived BMD and structural parameters. RESULTS: Eighteen women did not receive adjuvant hormone therapy, while 41 women received other therapy and 8 received AIs at baseline distributed similarly between RIS and PBO. Women on AIs and PBO were found to have the lowest BMD and indices. RIS improved BMD and several HSA indices at the intertrochanteric site in women regardless of their hormonal therapy, but most improvement was observed in women who were not on AIs (all p< or =0.05 except buckling ratio). Changes at the narrow neck and femoral shaft were similar. CONCLUSION: The use of AIs appears to lead to lower HSA-derived BMD and hip structural indices as compared to women on no or non-AI therapy in chemotherapy-induced postmenopausal breast cancer patients. Preventive therapy with once weekly oral risedronate maintains structural, skeletal integrity independently of the use of or type of adjuvant therapy.

Effect of risedronate on hip structural geometry: a 1-year, double-blind trial in chemotherapy-induced postmenopausal women.

INTRODUCTION: Chemotherapy-induced menopause is associated with bone loss. The effect on structural geometry is unknown. Our objective was to determine if oral bisphosphonate therapy could maintain or improve femoral geometry in breast cancer patients with chemotherapy-induced menopause. METHODS: This preplanned 1 year interim, secondary analysis of the Risedronate's Effect on Bone loss in Breast CAncer Study (REBBeCA Study) examined hip structure analysis (HSA), i.e. changes in the bone cross-sectional area (bone CSA), section modulus (SM: measure of bending strength), cortical thickness (CT) and buckling ratio (BR: index of cortical bone stability), in a double-blind trial of 87 newly postmenopausal, nonmetastatic breast cancer patients, randomized to risedronate, 35 mg once weekly (RIS) versus placebo (PBO). RESULTS: After 12 months, intertrochanteric parameters demonstrated percentage improvement (RIS vs. PBO) from baseline in bone CSA (mean+/-SD: 4.25+/-6.29 vs. 0.60+/-5.99%), SM (3.97+/-6.40 vs. 0.80+/-7.08%), and CT [5.20+/-6.98 vs. 1.13+/-6.87% (all p-values <0.05 except SM p=0,0643)]. Similar improvements were observed at the femoral shaft [bone CSA: 2.24+/-5.74 vs. -0.78+/-5.73%; SM: 1.62+/-6.23 vs. -1.39+/-7.06%; CT: 3.79+/-7.84 vs. -0.17+/-7.90% (all p-values <0.05, RIS vs. PBO, except SM p= p =0.0568)]. At both sites, the BR had significant decreases consistent with improved strength. CONCLUSION: We conclude that RIS improves measures of hip structural geometry in women with breast cancer following chemotherapy.