Karen T. Vujevich

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

PURPOSE Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort. PATIENTS AND METHODS Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. RESULTS At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. CONCLUSION We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.

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 Risedronates 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.

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 Becks 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.

Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized, controlled clinical trial

UNLABELLED This study provides preliminary evidence that risedronate not only preserves BMD but may also attenuate the loss of bone microarchitecture over 2years during a time of accelerated bone loss in post-menopausal breast cancer survivors on aromatase inhibitors. INTRODUCTION Accelerated bone loss and elevated fracture risk are associated with the use of aromatase inhibitors (AIs) in women with breast cancer. We previously reported that the oral bisphosphonate, risedronate, can maintain bone mineral density (BMD) in the hip and spine over 2-years in post-menopausal breast cancer survivors on AIs. In this study, we examined whether oral bisphosphonates can also preserve bone microarchitecture as measured by the trabecular bone score (TBS) in this population. METHODS This 2-year randomized, double-blind, placebo-controlled trial included postmenopausal women over age 55 with breast cancer on an AI who had low bone mass. Participants provided informed consent and were randomized to risedronate 35mg once weekly or placebo. We examined 12- and 24-month changes in spine TBS, analyzed using linear mixed models. RESULTS One-hundred and nine women with a mean age of 70.5years were included in the analysis. In the placebo group, BMD declined at the spine and hip over the 24-month period but was preserved in the active treatment group (data previously reported). TBS declined in the placebo group by -2.1% and -2.3% at 12- and 24-months, respectively (p<0.005). The TBS percent change in bisphosphonate-treated patients was -0.9% and -1.3% at 12 and 24-months but did not reach statistical significance (p=0.24 and 0.14). The 12- and 24-month between-group differences were 0.9 (p=0.38) and 0.8 (p=0.44) percentage points. TBS change correlated with spine BMD changes in the placebo group at 12- and 24-months (r=0.33 and 0.34, p<0.01) but not in the active treatment group. CONCLUSION The oral bisphosphonate risedronate preserves BMD and may attenuate loss of bone microarchitecture over 2years during a time of accelerated bone loss in breast cancer survivors on AIs, but more definitive evidence is needed.

Heel Ultrasound Can Assess Maintenance of Bone Mass in Women With Breast Cancer

Postmenopausal women with early stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer when compared with the current standard of bone mass measurement, dual-energy X-ray absorptiometry (DXA) and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8 yr) women with nonmetastatic breast cancer were randomized to risedronate, 35 mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional DXA-derived bone mineral density (BMD). Over 2 yr, bone mass assessed by heel QUS remained stable in women on risedronate, whereas women on placebo had a 5.2% decrease (p ≤ 0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p ≤ 0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r=0.50), femoral neck (r=0.40), and spine (r=0.46) at baseline (all p ≤ 0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women.