Hadji P, Kauka A, Ziller M, Birkholz K, Baier M, Muth M, Bauer M
Department of Obstetrics and Gynecology, Philipps-University of Marburg, Baldingerstrasse, 35033, Marburg, Germany,
Osteoporos Int. 2014 Apr;25(4):1369-78. doi: 10.1007/s00198-013-2615-z. Epub 2014 Feb 7.
The effects of bisphosphonates on altered bone turnover marker (BTM) levels associated with adjuvant endocrine or chemotherapy in early breast cancer have not been systematically investigated. In ProBONE II, zoledronic acid decreased these elevated BTM levels and increased bone mineral density (BMD) during adjuvant therapy, consistent with its antiresorptive effects.
Adjuvant chemotherapy or endocrine therapy for early hormone receptor-positive breast cancer (HR(+) BC) is associated with rapid BMD loss and altered BTM levels. Adjuvant bisphosphonate studies demonstrated BMD increases, but did not investigate BTM effects. The randomized, double-blind, ProBONE II study investigated the effect of adjuvant zoledronic acid (ZOL) on BMD and BTM in premenopausal women with early HR(+) BC.
Seventy premenopausal women with early HR(+) BC received adjuvant chemotherapy and/or endocrine therapy plus ZOL (4 mg IV every 3 months) or placebo for 24 months. Primary endpoint was change in lumbar spine BMD at 24 months versus baseline. Secondary endpoints included femoral neck and total femoral BMD changes, changes in BTM, and safety.
Lumbar spine BMD increased 3.14% from baseline to 24 months in ZOL-treated participants versus a 6.43% decrease in placebo-treated participants (P < 0.0001). Mean changes in T- and Z-scores, and femoral neck and total femoral BMD, showed similar results. Bone resorption marker levels decreased ∼ 55% in ZOL-treated participants versus increases up to 65% in placebo-treated participants (P < 0.0001 for between-group differences). Bone formation marker (procollagen I N-terminal propeptide) levels decreased ∼ 57% in ZOL-treated participants versus increases up to 45% in placebo-treated participants (P < 0.0001 for between-group differences). Adverse events were consistent with the established ZOL safety profile and included one case of osteonecrosis of the jaw after a tooth extraction.
Adding ZOL to adjuvant therapy improved BMD, reduced BTM levels, and was well tolerated in premenopausal women with early HR(+) BC receiving adjuvant chemotherapy and/or endocrine therapy.
双膦酸盐类药物对早期乳腺癌辅助内分泌治疗或化疗相关的骨转换标志物（BTM）水平改变的影响尚未得到系统研究。在ProBONE II研究中，唑来膦酸在辅助治疗期间降低了这些升高的BTM水平并增加了骨密度（BMD），与其抗吸收作用一致。
早期激素受体阳性乳腺癌（HR(+) BC）的辅助化疗或内分泌治疗与骨密度快速下降和BTM水平改变有关。辅助双膦酸盐类药物研究显示骨密度增加，但未研究BTM的影响。随机、双盲的ProBONE II研究调查了辅助唑来膦酸（ZOL）对绝经前早期HR(+) BC女性骨密度和BTM的影响。
70名绝经前早期HR(+) BC女性接受辅助化疗和/或内分泌治疗加ZOL（每3个月静脉注射4 mg）或安慰剂，为期24个月。主要终点是24个月时腰椎骨密度相对于基线的变化。次要终点包括股骨颈和全股骨骨密度变化、BTM变化以及安全性。
ZOL治疗组参与者从基线到24个月腰椎骨密度增加3.14%，而安慰剂治疗组参与者下降6.43%（P < 0.0001）。T值和Z值以及股骨颈和全股骨骨密度的平均变化显示出类似结果。ZOL治疗组参与者的骨吸收标志物水平下降约55%，而安慰剂治疗组参与者增加高达65%（组间差异P < 0.0001）。ZOL治疗组参与者的骨形成标志物（I型前胶原N端前肽）水平下降约57%，而安慰剂治疗组参与者增加高达45%（组间差异P < 0.0001）。不良事件与已确定的ZOL安全性概况一致，包括拔牙后1例颌骨坏死病例。
在辅助治疗中添加ZOL可改善骨密度、降低BTM水平，并且在接受辅助化疗和/或内分泌治疗的绝经前早期HR(+) BC女性中耐受性良好。
