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      Bone mineral loss induced by anticancer treatment for gynecological malignancies in premenopausal women

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          Abstract

          Objective

          Although surgical menopause may increase the risks of osteoporosis, few studies have investigated the influence of chemotherapy and radiation therapy. The aim of this study is to evaluate the effects of treatments for gynecological malignancies on bone mineral density (BMD).

          Methods

          This study enrolled 35 premenopausal women (15 ovarian cancers (OCs), 9 endometrial cancers (ECs), and 11 cervical cancers (CCs)) who underwent surgical treatment that included bilateral oophorectomy with or without adjuvant platinum-based chemotherapy in OC and EC patients, or concurrent chemo-radiation therapy (CCRT) in CC patients according to the established protocols at the Osaka Medical College Hospital between 2006 and 2008. The BMD of the lumbar spine (L1–L4) was measured by dual-energy X-ray absorptiometry, and urine cross-linked telopeptides of type I collagen (NTx) and bone alkaline phosphatase (BAP) were assessed for evaluation of bone resorption and bone formation respectively. These assessments were performed at baseline and 12 months after treatment.

          Results

          Although the serum BAP was significantly increased only in the CC group, a rapid increase in the bone resorption marker urinary NTx was observed in all groups. The BMD, 12 months after CCRT was significantly decreased in the CC group at 91.9±5.9% ( P<0.05 in comparison to the baseline).

          Conclusion

          This research suggests that anticancer therapies for premenopausal women with gynecological malignancies increase bone resorption and may reduce BMD, particularly in CC patients who have received CCRT. Therefore, gynecologic cancer survivors should be educated about these potential risks and complications.

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          Most cited references29

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          Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis.

          Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described. To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis. MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies. For the efficacy analysis, investigators selected studies that reported the rate of or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events; malignant conditions; and osteonecrosis. Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality. Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen-progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding. Few studies have directly compared different agents or classes of agents used to treat osteoporosis. Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, the data are insufficient to determine the relative efficacy or safety of these agents.
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            Effect of early menopause on bone mineral density and fractures.

            To review the data on the effect of early menopause on bone. Do women undergoing early menopause develop lower bone mineral density at an earlier age and do they have a higher incidence of osteoporotic fractures? Is there a difference on bone between women who undergo early natural menopause compared to women who have early menopause after oophorectomy? The earlier in life that menopause occurs, the lower the bone density will be later in life. Low bone density is associated with a higher fracture rate, and several studies show a relationship between early menopause, oophorectomy, and an increase in osteoporotic fractures. Early menopause is a risk factor for osteoporosis. Women with an early menopause should have bone density testing performed within 10 years of menopause so that osteopenia or osteoporosis will be diagnosed early and appropriate anti-resorptive therapy initiated.
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              Prophylactic oophorectomy in premenopausal women and long-term health.

              To review the data on long-term outcomes in women who underwent prophylactic bilateral oophorectomy, a common surgical procedure that has more than doubled in frequency since the 1960s. Literature review of the published data on the consequences of prophylactic bilateral oophorectomy. Special emphasis was given to the Mayo Clinic Cohort Study of Oophorectomy and Aging. Main outcome measures Overall mortality, cardiovascular disease, cognitive impairment and dementia, parkinsonism, osteoporosis, psychological wellbeing and sexual function. There is a growing body of evidence suggesting that the premature loss of ovarian function caused by bilateral oophorectomy performed before natural menopause is associated with several negative outcomes. In particular, studies have revealed an increased risk of premature death, cardiovascular disease, cognitive impairment or dementia, parkinsonism, osteoporosis and bone fractures, decline in psychological wellbeing and decline in sexual function. The effects involve different organs (e.g. heart, bone, or brain), and different functions within organs (e.g. cognitive, motor, or emotional brain functions). Estrogen treatment may prevent some but not all of these negative outcomes. The potential adverse effects of prophylactic bilateral oophorectomy on heart health, neurological health, bone health and quality of life should be carefully weighed against its potential benefits for cancer risk reduction in women at average risk of ovarian cancer.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                BioScientifica (Bristol )
                2049-3614
                19 November 2012
                01 March 2013
                : 2
                : 1
                : 11-17
                Affiliations
                [1 ]Department of Obstetrics and Gynecology Osaka Medical College 2-7 Daigaku-machi, Takatsuki-city, Osaka, 569-8686Japan
                Author notes
                Correspondence should be addressed to A Tanabe Email gyn074@ 123456poh.osaka-med.ac.jp
                Article
                EC120043
                10.1530/EC-12-0043
                3680962
                23781313
                90924277-41cb-4244-a3aa-6aa0517a5ce0
                © 2012 The Authors. Published by BioScientifica Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 September 2012
                : 11 October 2012
                Categories
                Research

                surgical menopause,concurrent chemo-radiation therapy,bone mineral density,cervical cancer

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