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    Original Investigation
    Genetics and Genomics
    August 7, 2019

    Changes in Bone Mineral Density After Prophylactic Bilateral Salpingo-Oophorectomy in Carriers of a BRCA Mutation

    Author Affiliations
    • 1Women’s College Research Institute, Toronto, Ontario, Canada
    • 2Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
    • 3Osteoporosis Program, University Health Network, Centre of Excellence in Skeletal Health Assessment, University of Toronto, Toronto, Ontario, Canada
    • 4Department of Gynecology Oncology, Princess Margaret Cancer Center, Toronto, Ontario, Canada
    JAMA Netw Open. 2019;2(8):e198420. doi:10.1001/jamanetworkopen.2019.8420
    Key Points español 中文 (chinese)

    Question  What is the association of preventive oophorectomy with bone health in individuals with a BRCA mutation?

    Findings  In this cohort study of 95 women with a BRCA mutation, prophylactic oophorectomy was associated with a decline in bone mineral density, which was most apparent among women who were premenopausal at surgery. Use of hormone therapy was associated with less bone loss.

    Meaning  Although limited by the small sample size, these findings support targeted management strategies to maintain bone health in this high-risk population.

    Abstract

    Importance  Preventive surgery is strongly recommended for individuals with a BRCA mutation at a young age to prevent ovarian cancer and improve overall survival. The overall effect of early surgical menopause on various health outcomes, including bone health, has not been clearly elucidated.

    Objective  To evaluate the association of prophylactic bilateral salpingo-oophorectomy with bone mineral density (BMD) loss among individuals with a BRCA mutation.

    Design, Setting, and Participants  This retrospective cohort study of participants with a BRCA mutation who underwent oophorectomy through the University Health Network, Toronto, Ontario, Canada, recruited participants from January 2000 to May 2013. Eligibility criteria included having a BRCA mutation, at least 1 ovary intact prior to surgery, and no history of any cancer other than breast cancer. Bone mineral density was measured using dual-energy x-ray absorptiometry before and after surgery. Data analysis began in December 2018 and finished in January 2019.

    Main Outcomes and Measures  The annual change in BMD from baseline to follow-up was calculated for the following 3 anatomical locations: (1) lumbar spine, (2) femoral neck, and (3) total hip.

    Results  A total of 95 women had both a baseline and postsurgery BMD measurement with a mean (SD) follow-up period of 22.0 (12.7) months. The mean (SD) age at oophorectomy was 48.0 (7.4) years. Among women who were premenopausal at time of surgery (50 [53%]), there was a decrease in BMD from baseline to follow-up across the lumbar spine (annual change, −3.45%; 95% CI, −4.61% to −2.29%), femoral neck (annual change, −2.85%; 95% CI, −3.79% to −1.91%), and total hip (annual change, −2.24%; 95% CI, −3.11% to −1.38%). Self-reported hormone therapy use was associated with significantly less bone loss at the lumbar spine (−2.00% vs −4.69%; P = .02) and total hip (−1.38% vs −3.21; P = .04) compared with no hormone therapy use. Among postmenopausal women at time of surgery (45 [47%]), there was also a significant decrease in BMD across the lumbar spine (annual change, −0.82%; 95% CI, −1.42% to −0.23%) and femoral neck (annual change, −0.68%; 95% CI, −1.33% to −0.04%) but not total hip (annual change, −0.18%; 95% CI, −0.82% to 0.46%).

    Conclusions and Relevance  This study found that oophorectomy was associated with postoperative bone loss, especially among women who were premenopausal at the time of surgery. Targeted management strategies should include routine BMD assessment and hormone therapy use to improve management of bone health in this population.

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