Evaluation of the protective effects of zoledronic acid on bone mass in premenopausal women undergoing adjuvant chemotherapy following treatment discontinuation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 562-562
Author(s):  
D. L. Hershman ◽  
D. McMahon ◽  
K. D. Crew ◽  
T. Shao ◽  
S. Cremers ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Adjuvant Chemotherapy ◽  
Bone Loss ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Secondary Outcome ◽  
First Year ◽  
Mineral Density ◽  
Double Blind ◽  
One Year

562 Background: Adjuvant chemotherapy is associated with a significant reduction in bone mineral density (BMD) in premenopausal women with breast cancer (BC). We previously showed that this loss of BMD can be prevented with zoledronic acid (ZA) every 3 months for a year. Since bone loss in women with osteoporosis is prevented with annual ZA, we examined whether protection from bone loss by ZA in women with BC persists following discontinuation of ZA. Methods: A randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg every 3 months) versus placebo for 1 year in premenopausal women with BC undergoing adjuvant chemotherapy was conducted. Patients had serial BMD measurement at 0 (after surgery and before chemotherapy), 6, 12 and 24 months. Demographic, clinical, and tumor characteristics were collected. Serum was stored at -70°C and analyzed in batches. The secondary outcome of percent change in BMD at 24 months, one year following the last ZA/placebo, is presented. Intention-to-treat analyses with linear mixed models were performed using SAS version 9. Results: Of 101 patients randomized, 85 completed 12 month, and 62 completed 24 month evaluations; mean age 41 (SD 5.2). Demographic and baseline characteristics were similar between treatment groups. By 24 months, 38 (61%) had not regained their menses; 22 patients were on tamoxifen, 25 were on an aromatase inhibitor. Chemotherapy without ZA was associated with a significant decline from baseline in lumbar spine (LS) BMD after both 12 (-5.4%) and 24 (-6.3%) months. Similarly total hip (TH) and femoral neck (FN) BMD declined by 2.6% and 2.4% by 24 months, respectively. In contrast, BMD remained stable in ZA-treated patients (p < 0.0001 vs placebo). Patients who received ZA had stable BMD at 24 months (LS -0.58%, TH 0.83%, FN 0.04%). Analysis of bone turnover markers is ongoing. Conclusions: Premenopausal women receiving adjuvant chemotherapy for BC had significant bone loss in the first year that persisted in the second year. ZA every 3 months for a year effectively prevented bone loss during the first year and 1 year after completion of ZA treatment. One year of ZA maintains BMD in premenopausal BC patients for an additional year after discontinuation of ZA. [Table: see text]

scholarly journals Zoledronic Acid Prevents Bone Loss in Premenopausal Women Undergoing Adjuvant Chemotherapy for Early-Stage Breast Cancer

2008 ◽  
Vol 26 (29) ◽  
pp. 4739-4745 ◽  
Author(s):  
Dawn L. Hershman ◽  
Donald J. McMahon ◽  
Katherine D. Crew ◽  
Serge Cremers ◽  
Dinaz Irani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Adjuvant Chemotherapy ◽  
Bone Loss ◽  
Repeated Measures ◽  
Early Stage ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Mineral Density ◽  
Percent Change

Purpose Adjuvant chemotherapy for breast cancer (BC) may be associated with increased rates of bone loss and decreased bone mineral density (BMD) and may lead to premature osteoporosis and increased fracture risk. We examined whether zoledronic acid (ZA) prevents bone loss in premenopausal women receiving chemotherapy for early-stage BC. Patients and Methods This study is a randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg intravenously every 3 months) versus placebo for 1 year. Premenopausal women underwent serial BMD measurements before initiating chemotherapy and at 6 and 12 months. The primary outcome was percent change in lumbar spine (LS) BMD at 6 months. Secondary outcomes were percent change at any BMD site and markers of bone turnover at 12 months. Linear mixed model analysis for repeated measures was performed. Results Of 101 women who were randomly assigned and completed baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12-month evaluation. Baseline characteristics were comparable between the groups. Mean age was 42 years. Placebo was associated with significant decline in LS BMD at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8% at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA patients (P < .0001 compared with placebo). Conclusion Premenopausal women receiving chemotherapy for BC sustained significant bone loss at the LS and hip, whereas BMD remained stable in women who received ZA. Administration of ZA during the first year of chemotherapy is an effective and well-tolerated strategy for preventing bone loss.

Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group

2007 ◽  
Vol 25 (7) ◽  
pp. 820-828 ◽  
Author(s):  
Michael F.X. Gnant ◽  
Brigitte Mlineritsch ◽  
Gero Luschin-Ebengreuth ◽  
Stephan Grampp ◽  
Helmut Kaessmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Endocrine Therapy ◽  
Premenopausal Women ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Mineral Density ◽  
T Score

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Zoledronic acid for the prevention of bone loss in patients with previously untreated lymphoma undergoing chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20611-e20611
Author(s):  
V. D. Cataldo ◽  
M. A. Thompson ◽  
B. B. Toth ◽  
P. Sanjorjo ◽  
S. J. Bourgeois ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Carbonate ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Periodontal Disease ◽  
Phase Iii ◽  
Exclusion Criterion ◽  
Mineral Density ◽  
Absolute Change ◽  
One Year

e20611 Background: Treatment of lymphoma with alkylating agents and steroids causes bone loss and increased fracture risk. In addition, over half of all untreated lymphoma patients are osteopenic or osteoporotic at diagnosis. Pamidronate reduces bone loss and risk of vertebral fractures in lymphoma patients undergoing chemotherapy (CT). However, the effects of the more potent bisphosphonate (BP) zoledronic acid (ZA) in this setting are unknown. Therefore, we report on a phase III trial evaluating the effect of ZA on bone mineral density (B) in patients with newly-diagnosed lymphoma undergoing CT. Methods: In total, 72 patients will be randomized to either the control arm [calcium carbonate (1,200 mg orally/day) plus vitamin D (400 IU orally/day)], or the BP arm [calcium carbonate and vitamin D as in the control arm plus ZA (4 mg IV at baseline and at 6 months)]. The primary endpoint is the absolute change in B of the lumbar spine (LS) and femoral neck (FN) at baseline and 12 months. Results: Thus far, 112 patients have been screened for enrollment. Twenty-seven patients (24.1%) failed screening due to periodontal disease, a predetermined exclusion criterion of the study. To date, 14 patients in the control arm and 9 patients in the BP arm have completed the one-year follow up period including baseline and one-year B evaluations. Comparing patients in the control arm to those in the BP arm, the average absolute change in B at the LS was -0.048 g/cm2 vs. 0.0093 g/cm2 (p=0.005), at the left FN was -0.039 g/cm2 vs. 0.0074 g/cm2 (p=0.01), and at the right FN was -0.043 g/cm2 vs. 0.0211 g/cm2 (p<0.001), respectively. There have been no therapy-related serious adverse events or skeletal fractures in either arm. Conclusions: ZA in combination with calcium carbonate and vitamin D improves the B of patients with lymphoma undergoing CT. Given the incidence of below-average pre-treatment B and the known deleterious effects of lymphoma therapy on bone density, baseline B evaluation is warranted in all lymphoma patients. The high rate of periodontal disease in this patient population emphasizes the need for careful dental evaluation prior to BP therapy given the well-described, albeit rare, risk of osteonecrosis of the jaw from ZA. [Table: see text]

scholarly journals Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer

2009 ◽  
Vol 27 (7) ◽  
pp. 1047-1053 ◽  
Author(s):  
Stephanie L. Hines ◽  
Betty Anne Mincey ◽  
Jeff A. Sloan ◽  
Sachdev P. Thomas ◽  
Elaine Chottiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Mineral Density ◽  
Double Blind ◽  
Treatment Groups ◽  
The Mean ◽  
Prevention Of Bone Loss ◽  
To Receive

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

Sign in / Sign up

Export Citation Format

Share Document