Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer

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

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Abstract

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.

Original languageEnglish
Article numbere0169673
JournalPLoS ONE
Volume12
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

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ovarian neoplasms
Bone Remodeling
Ovariectomy
breast neoplasms
Ovarian Neoplasms
Bone
bones
Breast Neoplasms
osteocalcin
Osteocalcin
peptides
normal values
Reference Values
menopause
Menopause
Collagen Type I
prospective studies
drug therapy
collagen
questionnaires

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Fakkert, I. E., Van Der Veer, E., Abma, E. M., Lefrandt, J. D., Wolffenbuttel, B. H. R., Oosterwijk, J. C., ... Mourits, M. J. E. (2017). Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer. PLoS ONE, 12(1), [e0169673]. https://doi.org/10.1371/journal.pone.0169673
Fakkert, Ingrid E. ; Van Der Veer, Eveline ; Abma, Elske Marije ; Lefrandt, Joop D. ; Wolffenbuttel, Bruce H.R. ; Oosterwijk, Jan C. ; Slart, Riemer H.J.A. ; Westrik, Iris G. ; De Bock, Geertruida H. ; Mourits, Marian J.E. / Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer. In: PLoS ONE. 2017 ; Vol. 12, No. 1.
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title = "Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer",
abstract = "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.",
author = "Fakkert, {Ingrid E.} and {Van Der Veer}, Eveline and Abma, {Elske Marije} and Lefrandt, {Joop D.} and Wolffenbuttel, {Bruce H.R.} and Oosterwijk, {Jan C.} and Slart, {Riemer H.J.A.} and Westrik, {Iris G.} and {De Bock}, {Geertruida H.} and Mourits, {Marian J.E.}",
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Fakkert, IE, Van Der Veer, E, Abma, EM, Lefrandt, JD, Wolffenbuttel, BHR, Oosterwijk, JC, Slart, RHJA, Westrik, IG, De Bock, GH & Mourits, MJE 2017, 'Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer' PLoS ONE, vol. 12, no. 1, e0169673. https://doi.org/10.1371/journal.pone.0169673

Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer. / Fakkert, Ingrid E.; Van Der Veer, Eveline; Abma, Elske Marije; Lefrandt, Joop D.; Wolffenbuttel, Bruce H.R.; Oosterwijk, Jan C.; Slart, Riemer H.J.A.; Westrik, Iris G.; De Bock, Geertruida H.; Mourits, Marian J.E.

In: PLoS ONE, Vol. 12, No. 1, e0169673, 01.01.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer

AU - Fakkert, Ingrid E.

AU - Van Der Veer, Eveline

AU - Abma, Elske Marije

AU - Lefrandt, Joop D.

AU - Wolffenbuttel, Bruce H.R.

AU - Oosterwijk, Jan C.

AU - Slart, Riemer H.J.A.

AU - Westrik, Iris G.

AU - De Bock, Geertruida H.

AU - Mourits, Marian J.E.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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Fakkert IE, Van Der Veer E, Abma EM, Lefrandt JD, Wolffenbuttel BHR, Oosterwijk JC et al. Elevated bone turnover markers after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer. PLoS ONE. 2017 Jan 1;12(1). e0169673. https://doi.org/10.1371/journal.pone.0169673