Elevated Bone Turnover Markers after Risk-Reducing Salpingo-Oophorectomy in Women at Increased Risk for Breast and Ovarian Cancer

Background
Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers. Premenopausal RRSO is hypothesized to increase fracture risk more than natural menopause. Elevated bone turnover markers (BTMs) might predict fracture risk. We investigated BTM levels after RRSO and aimed to identify clinical characteristics associated with elevated BTMs.
Methods
Osteocalcin (OC), procollagen type I N-terminal peptide (PINP) and serum C-telopeptide of type I collagen (sCTx) were measured in 210 women ≥ 2 years after RRSO before age 53. BTM Z-scores were calculated using an existing reference cohort of age-matched women. Clinical characteristics were assessed by questionnaire.
Results
BTMs after RRSO were higher than age-matched reference values: median Z-scores OC 0.11, p = 0.003; PINP 0.84, p < 0.001; sCTx 0.53, p < 0.001 (compared to Z = 0). After excluding women with recent fractures or BTM interfering medication, Z-scores increased to 0.34, 1.14 and 0.88, respectively. Z-scores for OC and PINP were inversely correlated to age at RRSO. No correlation was found with fracture incidence or history of breast cancer.
Conclusions
Five years after RRSO, BTMs were higher than age-matched reference values. Since elevated BTMs might predict higher fracture risk, prospective studies are required to evaluate the clinical implications of this finding.

研究背景
风险降低型输卵管卵巢切除术（Risk-reducing salpingo-oophorectomy, RRSO）可降低BRCA1/2突变携带者的卵巢癌发病风险。有假说认为，绝经前接受风险降低型输卵管卵巢切除术相较于自然绝经，会更高程度地增加骨折风险。骨转换标志物（bone turnover markers, BTMs）水平升高或可预测骨折风险。本研究旨在探究风险降低型输卵管卵巢切除术后的骨转换标志物水平，并明确与骨转换标志物水平升高相关的临床特征。

方法
本研究对210名已接受风险降低型输卵管卵巢切除术，且手术时年龄≤53岁、术后至少已过2年的女性，检测了其骨钙素（Osteocalcin, OC）、I型前胶原N末端肽（procollagen type I N-terminal peptide, PINP）以及血清I型胶原C末端肽（serum C-telopeptide of type I collagen, sCTx）水平。基于已有的年龄匹配女性参考队列计算骨转换标志物Z评分。通过问卷调查收集受试者的临床特征信息。

结果
风险降低型输卵管卵巢切除术后的骨转换标志物水平高于年龄匹配参考值：骨钙素中位Z评分为0.11（p=0.003），I型前胶原N末端肽中位Z评分为0.84（p<0.001），血清I型胶原C末端肽中位Z评分为0.53（p<0.001，与Z=0相比）。排除近期发生骨折或服用影响骨转换标志物检测的药物的女性后，上述Z评分分别升至0.34、1.14和0.88。骨钙素与I型前胶原N末端肽的Z评分与接受风险降低型输卵管卵巢切除术时的年龄呈负相关。未发现骨转换标志物Z评分与骨折发生率或乳腺癌病史存在相关性。

结论
风险降低型输卵管卵巢切除术后五年，骨转换标志物水平高于年龄匹配参考值。鉴于骨转换标志物水平升高或可预测更高的骨折风险，需开展前瞻性研究以评估该发现的临床意义。