Abstract P6-12-03: Effects of high dose of bisphosphonate therapy on bone microarchitecture of the peripheral skeleton in women with early stage breast cancer
Authors: Shao T , Shane ES , McMahon D , Crew KD , Kalinsky K , Maurer M , Brown M , Gralow JR , Hershman DL 
Published: August 2014

Background: Randomized studies investigating adjuvant bisphosphonates in women with breast cancer are ongoing. While bisphosphonates would be expected to prevent the deterioration of bone microarchitecture that accompanies hormone or chemotherapy, complete suppression of osteoclast activity for prolonged periods of time can decrease repair of micro-cracks, and possibly lead to decreased bone strength. While bone strength is governed by the amount of bone present, trabecular and cortical components of bone microarchitecture also contribute independently to bone strength. We aimed to characterize the effects of long-term bisphosphonates on bone microarchitecture in women with breast cancer using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia.

Methods: We conducted a cross-sectional study involving early stage breast cancer patients treated with bisphosphonates on the S0307 clinical trial. Women were randomized to receive zoledronic acid, oral clodronate or oral ibandronate in doses far higher than those used in osteoporosis treatment as per protocol. After 18–36 months of bisphosphonate therapy, participates underwent a one-time evaluation of areal bone mineral density (aBMD) of the 1/3 radius, lumbar spine, and hip by dual energy x-ray absorptiometry (DXA), and cortical and trabecular volumetric BMD (vBMD) and trabecular microarchitecture of the radius and tibia by HR-pQCT. HR-pQCT measurements were compared to healthy young premenopausal women and age-matched Caucasian women.

Results: Baseline characteristics of the 12 enrolled patients: median age of 53 (range 40–67); white/Hispanics 7/5; pre/postmenopausal 4/8; mean body mass index 28.7 kg/m2 (20.9–34.8); average time on bisphosphonates 20 months (18–30); zoledronic acid/clodronate/ibandronate 5/6/1. The median aBMD DXA T-score of the 1/3 radius, lumbar spine and total hip were normal at +0.3, +0.1, and +0.2, respectively. Mean total, cortical, and trabecular vBMD of the radius as measured by HR-pQCT were 330±71, 905±55, and 146±35 mg hydroxyapatite/cm3, respectively. Mean cortical thickness was 0.803±0.170 mm, and mean trabecular number was 1.9±0.2. Mean total, cortical, and trabecular vBMD of the tibia were 285±54, 880±54, and 150±38 mg hydroxyapatite/cm3, respectively. Mean cortical thickness was 1.135±0.264 mm, and mean trabecular number was 1.7±0.3. There were no statistically significant differences between study group and each control. However, results were more similar to healthy young premenopausal control than the age-matched control.

Conclusion: Women on long-term bisphosphonate therapy for breast cancer had normal aBMD by DXA and normal cortical and trabecular vBMD, cortical thickness and trabecular number at the peripheral skeleton compared to healthy young women and age-matched women. This preliminary data is reassuring for cancer survivors if benefits from this therapy are established in the adjuvant setting.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-12-03.