Annegreet G Veldhuis-Vlug1,2, Gina N Woods3,4, Sigurdur Sigurdsson5, Susan K Ewing6, Phuong T Le1, Trisha F Hue6, Eric Vittinghoff6, Kaipin Xu7, Vilmundur Gudnason5,8, Gunnar Sigurdsson5, Deborah M Kado3,9, Gudny Eiriksdottir5, Tamara Harris10, Anne L Schafer6,11,12, Xiaojuan Li7, Mone Zaidi13, Clifford J Rosen1, Ann V Schwartz6. 1. Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, ME, USA. 2. Center for Bone Quality, Department of Endocrinology, Leiden University Medical Center, ZA Leiden, The Netherlands. 3. Department of Medicine, UC San Diego, La Jolla, CA, USA. 4. VA San Diego Healthcare System, San Diego, CA, USA. 5. Icelandic Heart Association Research Institute, Kopavogur, Iceland. 6. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA. 7. Program of Advanced Musculoskeletal Imaging (PAMI), Cleveland Clinic, Cleveland, OH, USA. 8. Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 9. Department of Family Medicine and Public Health, UC San Diego, La Jolla, CA, USA. 10. National Institute on Aging, National Institutes of Health (NIA, NIH), Bethesda, MD, USA. 11. Department of Medicine, University of California San Francisco, San Francisco, CA, USA. 12. Endocrine Research Unit, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. 13. The Mount Sinai Bone Program and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
CONTEXT: Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass. OBJECTIVE: To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Older adults from the AGES-Reykjavik Study, an observational cohort study. MAIN OUTCOME MEASURES: Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition. RESULTS: In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome. CONCLUSIONS: Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.
CONTEXT: Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass. OBJECTIVE: To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Older adults from the AGES-Reykjavik Study, an observational cohort study. MAIN OUTCOME MEASURES: Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition. RESULTS: In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome. CONCLUSIONS: Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.
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