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

Ingrid E Fakkert,Iris G Westrik,Riemer H J A Slart,Elske Marije Abma,Eveline Van Der Veer,Geertruida H De Bock,Joop D Lefrandt,Jan C Oosterwijk,Marian J E Mourits,Bruce H R Wolffenbuttel

doi:10.1371/journal.pone.0169673

Ingrid E Fakkert, Iris G Westrik + Show 8 more

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https://doi.org/10.1371/journal.pone.0169673

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BackgroundRisk-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.MethodsOsteocalcin (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.ResultsBTMs 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.ConclusionsFive 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.

Highlights

Women from families with a high incidence of breast and ovarian cancer have increased risks of both these cancers, especially women with a germline mutation in the BRCA1 or BRCA2 genes [1,2]
bone turnover markers (BTMs) after Risk-reducing salpingo-oophorectomy (RRSO) were higher than age-matched reference values: median Z-scores OC 0.11, p = 0.003; procollagen type I N-terminal peptide (PINP) 0.84, p < 0.001; sCTx 0.53, p < 0.001
Five years after RRSO, BTMs were higher than age-matched reference values

Summary

Introduction

Women from families with a high incidence of breast and ovarian cancer (hereditary breast and ovarian cancer; HBOC) have increased risks of both these cancers, especially women with a germline mutation in the BRCA1 or BRCA2 genes [1,2]. Risk-reducing salpingo-oophorectomy (RRSO) is advised to all BRCA1 and BRCA2 mutation carriers between age 35–40 and 40–45 respectively [3,4]. It is hypothesized that surgical menopause as induced by premenopausal RRSO increases fracture risk more than natural menopause, because of earlier age at menopause and acute and complete cessation of ovarian hormone production [5,6]. Assessment of bone turnover by measuring bone turnover marker (BTM) levels after RRSO may be a useful addition to BMD measurement. BTMs in blood or urine might predict fracture risk independently of BMD [12,13]. 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

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