Oostra Drew R, Lustberg Maryam B, Reinbolt Raquel E, Pan Xueliang, Wesolowski Robert, Shapiro Charles L
The Ohio State University Wexner Medical Center, Columbus, OH, USA.
The Breast Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.
Mol Cell Endocrinol. 2015 Feb 15;402:51-6. doi: 10.1016/j.mce.2014.12.028. Epub 2015 Jan 6.
Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF.
Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea.
Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm(2) to 0.976 g/cm(2) and 0.937 g/cm(2) at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70).
In what was likely a compensatory response to rapid bone loss, CIOF patients' OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF.
化疗所致卵巢功能衰竭（CIOF）会导致快速骨质流失。核因子κB受体激活剂（RANK）-RANK配体（RANK-L）信号传导平衡骨吸收与骨形成。骨保护素（OPG）作为RANK的诱饵受体，可中断破骨细胞激活及骨吸收。本研究探讨了CIOF女性中OPG与骨质流失之间的关系。
对接受辅助化疗的I/II期乳腺癌绝经前女性在化疗开始时、6个月及12个月时进行评估。连续测量腰椎（LS）和股骨颈（FN）的骨密度（BMD）、促卵泡激素（FSH）、离子钙、骨钙素和OPG。CIOF定义为妊娠试验阴性、FSH水平>30 mIU/mL且闭经≥3个月。
共纳入40名女性；31名（77.5%）符合CIOF标准。CIOF组在两个时间点的BMD均显著下降（p<0.001）：LS BMD在6个月和12个月时分别从中位数0.993 g/cm²降至0.976 g/cm²和0.937 g/cm²。OPG在6个月时显著升高（中位数增加0.30 pmol/L，p = 0.015），然后在12个月时下降至仍高于基线的水平（中位数差异0.2 pmol/L，p = 0.70）。
作为对快速骨质流失可能的代偿反应，CIOF患者的OPG水平在6个月时升高，然后在12个月时下降至高于基线评估的值。这种现象在其他疾病中有描述，但在CIOF中从未有过。
