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      Changes in bone metabolic profile associated with pregnancy or lactation

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          Abstract

          Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

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          Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts.

          Estrogen prevents osteoporotic bone loss by attenuating bone resorption; however, the molecular basis for this is unknown. Here, we report a critical role for the osteoclastic estrogen receptor alpha (ERalpha) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERalpha in differentiated osteoclasts (ERalpha(DeltaOc/DeltaOc)) and found that ERalpha(DeltaOc/DeltaOc) females, but not males, exhibited trabecular bone loss, similar to the osteoporotic bone phenotype in postmenopausal women. Further, we show that estrogen induced apoptosis and upregulation of Fas ligand (FasL) expression in osteoclasts of the trabecular bones of WT but not ERalpha(DeltaOc/DeltaOc) mice. The expression of ERalpha was also required for the induction of apoptosis by tamoxifen and estrogen in cultured osteoclasts. Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs.
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            Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study.

            Musculoskeletal diseases, especially osteoarthritis (OA) and osteoporosis (OP), impair activities of daily life (ADL) and quality of life (QOL) in the elderly. Although preventive strategies for these diseases are urgently required in an aging society, epidemiological data on these diseases are scant. To clarify the prevalence of knee osteoarthritis (KOA), lumbar spondylosis (LS), and osteoporosis (OP) in Japan, and estimate the number of people with these diseases, we started a large-scale population-based cohort study entitled research on osteoarthritis/osteoporosis against disability (ROAD) in 2005. This study involved the collection of clinical information from three cohorts composed of participants located in urban, mountainous, and coastal areas. KOA and LS were radiographically defined as a grade of > or =2 by the Kellgren-Lawrence scale; OP was defined by the criteria of the Japanese Society for Bone and Mineral Research. The 3,040 participants in total were divided into six groups based on their age: or =80 years. The prevalence of KOA in the age groups or =80 years 0, 9.1, 24.3, 35.2, 48.2, and 51.6%, respectively, in men, and the prevalence in women of the same age groups was 3.2, 11.4, 30.3, 57.1, 71.9, and 80.7%, respectively. With respect to the age groups, the prevalence of LS was 14.3, 45.5, 72.9, 74.6, 85.3, and 90.1% in men, and 9.7, 28.6, 41.7, 55.4, 75.1, and 78.2% in women, respectively. Data of the prevalence of OP at the lumbar spine and femoral neck were also obtained. The estimated number of patients with KOA, LS, and L2-L4 and femoral neck OP in Japan was approximately 25, 38, 6.4, and 11 million, respectively. In summary, we estimated the prevalence of OA and OP, and the number of people affected with these diseases in Japan. The ROAD study will elucidate epidemiological evidence concerning determinants of bone and joint disease.
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              Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis.

              Changes of bone turnover with aging are responsible for bone loss and play a major role in osteoporosis. Although an increase of bone turnover has been documented at the time of menopause, the subsequent abnormalities of bone resorption and formation and their potential role in determining bone mass in the elderly have not been investigated. To address this issue, we have measured a battery of new sensitive and specific markers of bone turnover in a population-based study of 653 healthy women analyzed cross-sectionally, including 432 women postmenopausal from 1 to 40 years, and the data were correlated with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at different skeletal sites. Bone formation was assessed by serum osteocalcin (OC), serum bone-specific alkaline phosphatase (B-ALP), serum C-propeptide of type I collagen (PICP), and bone resorption by the urinary excretion of two pyridinoline cross-linked peptides (NTX and CTX). Bone turnover increased in perimenopausal women with both irregular menses and elevated serum follicle stimulating hormone (FSH). Menopause induced a 37-52% and 79-97% increase in the bone formation and bone resorption marker levels, respectively (p < 0.0001 except for PICP). In postmenopausal women, bone formation markers did not decrease with age. When resorption markers were corrected by whole body bone mineral content (BMC), the fraction of bone resorbed per day was not correlated with age in postmenopausal women and remained elevated for up to 40 years after menopause. In premenopausal women, the bone turnover rate accounted for only 0-10% of the variation in whole body BMC, total hip, distal radius, and lumbar spine BMD. With increasing time after menopause, the importance of the bone turnover rate as a determinant of bone mass increased at all sites and accounted for up to 52% of the BMD variance in elderly women. Thus, in women 20 years or more postmenopause, bone turnover was higher in those in the lowest quartile than in those in the highest quartile of BMD. In elderly women, 20 years since menopause and over, but not in younger ones, serum PTH was negatively correlated with serum 25-hydroxyvitamin D (r = -0.22, p < 0.05) and explained only 5-8% of the bone turnover variance (p < 0.01-0.001). These data indicate that the overall rates of both bone formation and bone resorption remain high in elderly women. The rate of bone turnover appears to play an increasing role as a determinant of bone mass with increasing time since menopause with a high bone turnover rate being associated with a low bone mass. Thus assessing bone marker levels may be useful in the evaluation of osteoporosis risk. In elderly women, secondary hyperparathyroidism caused in part by reduced serum 25-hydroxyvitamin D appears to be a marginal determinant of an increased bone turnover rate.
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                Author and article information

                Contributors
                miyamoto.takeshi@kuh.kumamoto-u.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                13 May 2019
                13 May 2019
                2019
                : 9
                : 6787
                Affiliations
                [1 ]ISNI 0000 0004 1936 9959, GRID grid.26091.3c, Department of Orthopedic Surgery, , Keio University School of Medicine, ; 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 Japan
                [2 ]ISNI 0000 0004 1936 9959, GRID grid.26091.3c, Department of Advanced Therapy for Musculoskeletal Disorders, , Keio University School of Medicine, ; 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 Japan
                [3 ]ISNI 0000 0004 1936 9959, GRID grid.26091.3c, Department of Obstetrics and Gynecology, , Keio University School of Medicine, ; 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 Japan
                [4 ]ISNI 0000 0000 9290 9879, GRID grid.265050.4, Department of Environmental and Occupational Health, , School of Medicine, Toho University, ; 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540 Japan
                [5 ]ISNI 0000 0001 0660 6749, GRID grid.274841.c, Department of Orthopaedic Surgery, , Faculty of Life Sciences, Kumamoto University, ; Kumamoto, Japan
                Author information
                http://orcid.org/0000-0003-2395-9591
                Article
                43049
                10.1038/s41598-019-43049-1
                6513862
                31086225
                5a1df34d-5c5f-4488-b054-17f0793e323a
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 September 2018
                : 15 April 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100009619, Japan Agency for Medical Research and Development (AMED);
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                osteoporosis,prognostic markers
                Uncategorized
                osteoporosis, prognostic markers

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