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

Abstract

Purpose 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 aromatase inhibitor (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.

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG

“…Additionally, the adjusted differences in bone turnover markers 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) [107].…”

Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

“…AI therapy is recommended to reduce the risk of cancer recurrence in postmenopausal women with hormone receptor–positive breast cancer but has been reported to increase bone turnover, bone loss, and fracture risk . Concomitant bisphosphonate therapy and more recently denosumab are therapeutic options to prevent bone loss in AI users . Although one position paper has offered guidance on prevention of bone loss and fractures in postmenopausal women treated with AI for breast cancer that incorporates FRAX in the algorithm, the authors highlight concerns that FRAX was not designed to assess fracture risk in this setting and its accuracy is unknown …”

Integral strategy to supportive care in breast cancer survivors through occupational therapy and a m-health system: design of a randomized clinical trial

“…Body mass index, fat mass, lean body mass, abdominal adipose tissue and bone mineral density will also be assessed by conducting Dual-energy X-ray absorptiometry (DXA, Discovery densitometer from HOLOGIC, QDR 4500 W) using protocols reported in previous studies [43, 44]. This assessment tool has previously been used in breast cancer patients [45, 46]. …”