Prevention of Anastrozole-Induced Bone Loss with Monthly Oral Ibandronate during Adjuvant Aromatase Inhibitor Therapy for Breast Cancer

Abstract

Purpose: The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole. Experimental Design: BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo. Results: After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone^specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively). Conclusions: Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.

Osteonecrosis of the jaw and use of bisphosphonates in adjuvant breast cancer treatment: a metanalysis

“…Of these trials, six were excluded since data regarding the osteonecrosis of the jaw could not be retrieved. Finally, 15 trials were included in the meta-analysis [7,8,10,17,[22][23][24][25][26][27][28][29][30][31][32].…”

“…Table 1 presents the characteristics of the 15 trials that met our eligibility criteria. Nine studies (7,990 patients) used the bisphosphonate zoledronic acid [7, 8, 17, 22, 24-26, 28, 32], two trials (1,351 patients) used clodronate [29,31], two trials (350 patients) used risedronate [23,27], one pamidronate (953 patients) [30] and one ibandronate (50 patients) [10].…”

“…Four of the trials were double-blinded [10,23,27,31]. Randomization model, allocation concealment, and withdrawal description were evaluated in only eight eligible trials published in full text.…”

“…Two trials [26,31] described in detail the mode of randomization and the mode of allocation concealment. Withdrawals were described in detail in all eight trials published in full text [7,8,10,17,26,[29][30][31].…”

“…Evidence from clinical trials suggests that use of bisphosphonates in adjuvant setting may be effective in the treatment and prevention of CTIBL [7][8][9][10].…”