Skip to main content
SpringerLink
Log in
Book cover

Osteoporosis pp 239–257Cite as

Effects of Estrogens and SERMs on Bone Metabolism: Clinical Aspects

  • Chapter
  • First Online:

  • 1796 Accesses

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Estrogens and selective estrogen receptor modulators (SERMs) have potent skeletal effects that inhibit bone loss and reduce fracture risk. These agents were selected for prevention and treatment of bone loss based on an understanding of the normal menstrual cycle and elucidation of the pathophysiology of postmenopausal bone loss. Full-strength hormone or estrogen therapy appears to have a stronger effect on bone mineral density than SERMs, and more potently reduce fracture risk. Clinical prescriptions for hormone and estrogen therapy decreased significantly after the Women’s Health Initiative Hormone and Estrogen-Alone clinical trials were published in 2002 and 2004, respectively. Hormone and estrogen use have rebounded somewhat over the last decade with the availability of low-dose and transdermal preparations. SERMs have less potent effect than estrogen on increasing bone mineral density (BMD) or reducing fracture risk due largely to their partially antagonistic effects on the estrogen receptor. SERMs have advantages over estrogen in that they minimize the risk of some adverse effects related to estrogen, and have opposite effects than estrogen in other settings. Individual SERMs have unique tissue-specific activities that require documentation in clinical trials, as the clinical profiles of SERMs are moderately variable. The future of SERMs appears to be rich with possibilities, but successful clinical application has been slowed by their variable tissue-specific effects.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Treloar AE, Boynton RE, Benn BG, Brown BW. Variation in human menstrual cycle through reproductive life. Int J Fertil. 1967;12(1 Pt 2):77–126.

    CAS  PubMed  Google Scholar 

  2. Baldwin RM, Whalley PJ, Pritchard PR. Measurements of menstrual blood loss. Am J Obstet Gynecol. 1961;81:739–42.

    Article  CAS  PubMed  Google Scholar 

  3. Midgely AR Jr, Jaffe RB. Regulation of gonadotropins. IV. Correlations of serum concentrations of follicle stimulating and luteinizing hormones during the menstrual cycle. J Clin Endocrinol Metab. 1968;28(12):1699–703.

    Article  Google Scholar 

  4. Knobil E. The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res. 1980;36:53–88.

    CAS  PubMed  Google Scholar 

  5. Midgely AR Jr, Jaffe RB. Regulation of human gonadotropins. X. Episodic fluctuation of LH during the menstrual cycle. J Clin Endocrinol Metab. 1971;33(6):962–9.

    Article  Google Scholar 

  6. Soules MR, Steiner RA, Clifton DK, Cohen NL, Aksel S, Bremner WJ. Progesterone modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab. 1984;58(2):378–83.

    Article  CAS  PubMed  Google Scholar 

  7. Lloyd CW, Lobotsky J, Weisz J, Baird DT, McCracken JA, Pupkin M, et al. Concentration of unconjugated estrogens, androgens, and gestagens in ovarian and peripheral venous plasma of women: the normal menstrual cycle. J Clin Endocrinol Metab. 1971;32(2):155–66.

    Article  CAS  PubMed  Google Scholar 

  8. Bass S, Delmas PD, Pearce G, Hendrich E, Tabensky A, Seeman E. The differing tempo of growth in bone size, mass and density in girls is region-specific. J Clin Invest. 1999;104(6):795–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Garn SM. The course of bone gain and the phases of bone loss. Orthop Clin North Am. 1972;3(3):503–20.

    CAS  PubMed  Google Scholar 

  10. Bachrach LK, Hastie T, Wang M-C, Narasimhan B, Marcus R. Bone mineral acquisition in healthy Asian, Hispanic, Black, and Caucasian youth. A longitudinal study. J Clin Endocrinol Metab. 1999;84(12):4702–12.

    CAS  PubMed  Google Scholar 

  11. Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, et al. The Bone Mineral Density in Childhood Study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab. 2007;92(6):2087–99.

    Article  CAS  PubMed  Google Scholar 

  12. Gilsanz V, Boechat MI, Rote TF, Loro ML, Sayre JW, Goodman WG. Gender differences in vertebral body sizes in children and adolescents. Radiology. 1994;190(2):673–7.

    Article  CAS  PubMed  Google Scholar 

  13. Riggs BL, Khosla S, Melton LJ. Sex steroids and the construction and conservation of the adult skeleton. Endocrine Rev. 2002;23(3):279–302.

    Article  CAS  Google Scholar 

  14. Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, et al. A population-based study of age and sex differences in bone volumetric density, size, geometry and structure at different skeletal sites. J Bone Miner Res. 2004;19(12):1945–54.

    Article  PubMed  Google Scholar 

  15. Black AJ, Topping J, Durham B, Farquharson RG, Fraser WD. A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy. J Bone Miner Res. 2000;15(3):557–63.

    Article  CAS  PubMed  Google Scholar 

  16. Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, et al. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res. 2008;23(2):205–14.

    Article  PubMed  Google Scholar 

  17. Sfeir JG, Drake MT, Atkinson EJ, Achenbach SJ, Camp JJ, Tweed AJ, et al. Evaluation of cross-sectional and longitudinal changes in volumetric bone mineral density in postmenopausal women using single- versus dual-energy quantitative computed tomography. Bone. 2018;112:145–52.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Khosla S, Monroe DG. Regulation of bone metabolism by sex steroids. Cold Spring Harb Perspect Med. 2018;8(1). pii: a031211.

    Article  CAS  Google Scholar 

  19. Farr JN, Khosla S. Skeletal changes through the lifespan – from growth to senescence. Nat Rev Endocrinol. 2015;11(9):513–21.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Farr JN, Roforth MM, Fujita K, Nicks KM, Cunningham JM, Atkinson EJ, et al. Effects of age and estrogen on skeletal gene expression in humans as assessed by RNA sequencing. PLoS One. 2015;10(9):e0138347.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Buehring B, Hansen KE, Lewis BL, Cummings SR, Lane NE, Binkley N, et al.; Osteoporotic Fractures in Men (MrOS) Study Research Group. Dysmobility syndrome independently increases fracture risk in the osteoporotic fractures in men (MrOS) prospective cohort study. J Bone Miner Res. 2018;33(9):1622–9.

    Article  PubMed  Google Scholar 

  22. Khosla S, Farr JN, Kirkland JL. Inhibiting cellular senescence: a new therapeutic paradigm for age-related osteoporosis. J Clin Endocrinol Metab. 2018;103(4):1282–90.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL, et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23(9):1072–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Farr JN, Fraser DG, Wang H, Jaehn K, Ogrodnik MB, Weivoda MM, Drake MT, Tchkonia T, LeBrasseur NK, Kirkland JL, Bonewald LF, Pignolo RJ, Monroe DG, Khosla S. Identification of senescent cells in the bone microenvironment. J Bone Miner Res. 2016;31(11):1920–9.

    Article  CAS  PubMed  Google Scholar 

  25. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al.; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.

    Google Scholar 

  26. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al.; Women’s Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA. 2003;290(13):1729–38.

    Google Scholar 

  27. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al.; Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701–12.

    Google Scholar 

  28. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310(13):1353–68.

    Article  CAS  PubMed  Google Scholar 

  29. The Writing Group for the PEPI. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA. 1996;276(17):1389–96.

    Article  Google Scholar 

  30. Ravn P, Bidstrup M, Wasnich RD, et al. Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results of from the early postmenopausal intervention cohort study. A randomized, controlled trial. Ann Intern Med. 1999;131(12):935–42.

    Article  CAS  PubMed  Google Scholar 

  31. Christiansen C, Riis BJ. 17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women. J Clin Endocrinol Metab. 1990;71(4):836–41.

    Article  CAS  PubMed  Google Scholar 

  32. Greenwald MW, Gluck OS, Lang E, Rakov V. Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects. Menopause. 2005;12(6):741–8.

    Article  PubMed  Google Scholar 

  33. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA. 2001;285(22):2891–7.

    Article  CAS  PubMed  Google Scholar 

  34. Grodstein F, Stampfer MJ, Falkeborn M, Naessen T, Persson I. Postmenopausal hormone therapy and risk of cardiovascular disease and hip fracture in a cohort of Swedish women. Epidemiology. 1999;10(5):476–80.

    Article  CAS  PubMed  Google Scholar 

  35. Kiel DP, Felson DT, Anderson JJ, Wilson PW, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study. N Engl J Med. 1987;317(19):1169–74.

    Article  CAS  PubMed  Google Scholar 

  36. Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR. Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Ann Int Med. 1995;122(1):9–16.

    Article  CAS  PubMed  Google Scholar 

  37. Wasnich RD, Bagger YZ, Hosking DJ, et al.; Early Postmenopausal Intervention Cohort Study Group. Changes in bone density and turnover after alendronate or estrogen withdrawal. Menopause. 2004;11(6 Pt 1):622–30.

    Article  PubMed  Google Scholar 

  38. Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, et al.; WHI Investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299(9):1036–45.

    Article  CAS  PubMed  Google Scholar 

  39. LaCroix ZA, Chlebowski RT, Manson JE, Aragaki AK, Johnson KC, Martin L, et al.; WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305(13):1305–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Karim R, Dell RM, Greene DF, Mack WJ, Gallagher JC, Hodis HN. Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization. Menopause. 2011;18(11):1172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Watts NB, Cauley JA, Jackson RD, et al.; Women’s Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the women’s health initiative. J Clin Endocrinol Metab. 2017;102(1):302–8.

    Google Scholar 

  42. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728–53.

    Article  Google Scholar 

  43. Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, Santen RJ. Treatment of symptoms of the menopause: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975–4011.

    Article  CAS  PubMed  Google Scholar 

  44. Cobin RH, Goodman NF; AACE Reproductive Endocrinology Scientific Committee. American Association Of Clinical Endocrinologists And American College Of Endocrinology Position Statement on menopause-2017 update. Endocr Pract 2017;23(7):869–880.

    Google Scholar 

  45. Qaseem A, Forciea MA, McLean RM, Denberg TD, Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818–39.

    Article  PubMed  Google Scholar 

  46. ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol. 2014;123(1):202–16.

    Google Scholar 

  47. Starkey NJE, Li Y, Drenkhahn-Weinaug SK, Liu J, Lubahn DB. 27-hydroxycholesterol is an estrogen receptor β-selective negative allosteric modifier of 17β-estradiol binding. Endocrinology. 2018;159(5):1972–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Smith CL, Nawaz Z, O’Malley BW. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol. 1997;11(6):657–66.

    Article  CAS  PubMed  Google Scholar 

  49. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 2000;103(6):843–52.

    Article  CAS  PubMed  Google Scholar 

  50. McDonnell DP, Clemm DL, Hermann T, Goldman ME, Pike JW. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol. 1995;9(6):659–69.

    CAS  PubMed  Google Scholar 

  51. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998;95(7):927–37.

    Article  CAS  PubMed  Google Scholar 

  52. Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature. 1997;387(6634):733–6.

    Article  CAS  PubMed  Google Scholar 

  53. de Gooyer ME, Deckers GH, Schoonen WG, Verheul HA, Kloosterboer HJ. Receptor profiling and endocrine actions of tibolone. Steroids. 2003;68(1):21–30.

    Article  PubMed  Google Scholar 

  54. Billon-Galés A, Fontaine C, Filipe C, Douin-Echinard V, Fouque MJ, Flouriot G, et al. The transactivating function 1 of estrogen receptor alpha is dispensable for the vasculoprotective actions of 17beta-estradiol. Proc Natl Acad Sci U S A. 2009;106(6):2053–8.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zwart W, de Leeuw R, Rondaij M, Neefjes J, Mancini MA, Michalides R. The hinge region of the human estrogen receptor determines functional synergy between AF-1 and AF-2 in the quantitative response to estradiol and tamoxifen. J Cell Sci. 2010;123(Pt 8):1253–61.

    Article  CAS  PubMed  Google Scholar 

  56. Dickey RP, Holtkamp DE. Development, pharmacology, and clinical experience with clomiphene citrate. Hum Reproduct Update. 1996;2(6):483–506.

    Article  CAS  Google Scholar 

  57. Goldstein SR, Duvernoy CS, Calaf J, Adachi JD, Mershon JL, Dowsett SA, Agnusdei D, Stuenkel CA. Raloxifene use in clinical practice: efficacy and safety. Menopause. 2009;16(2):413–21.

    Article  PubMed  Google Scholar 

  58. Jordan VC. A century of deciphering the control mechanisms of sex steroid action in breast and prostate cancer: the origins of targeted therapy and chemoprevention. Cancer Res. 2009;69(4):1243–54.

    Article  CAS  PubMed  Google Scholar 

  59. Pickar JH, Macneil T, Ohleth K. SERMs: Progress and future perspectives. Maturitas. 2010;67(2):129–38.

    Article  CAS  PubMed  Google Scholar 

  60. Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors ERα and β. Endocrinology. 1997;138(3):863–70.

    Article  CAS  PubMed  Google Scholar 

  61. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337(23):1641–7.

    Article  CAS  PubMed  Google Scholar 

  62. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999;282(7):637–45.

    Article  CAS  PubMed  Google Scholar 

  63. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281(23):2189–97.

    Article  CAS  PubMed  Google Scholar 

  64. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al.; Raloxifene Use for The Heart (RUTH) Trial Investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355(2):125–37.

    Article  CAS  PubMed  Google Scholar 

  65. Vogel VG, Constantino JP, Wickerham JP, Cronin WM, Cecchini RS, Atkins JN, et al.; National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes. JAMA. 2006;295(23):2727–41.

    Google Scholar 

  66. Gushima M, Kawate H, Ohnaka K, Nomura M, Takayanagi R. Raloxifene induces nucleolar translocation of the estrogen receptor. Mol Cell Endocrinol. 2010;319(1–2):14–22.

    Article  CAS  PubMed  Google Scholar 

  67. Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-cause mortality. Am J Med. 2010;123(5):469.e1–7.

    Article  CAS  Google Scholar 

  68. Jacobsen DE, Samson MM, Emmelot-Vonk MH, Verhaar HJ. Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial. Eur J Endocrinol. 2010;162(2):371–6.

    Article  CAS  PubMed  Google Scholar 

  69. Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res. 2008;23(4):525–35.

    Article  CAS  PubMed  Google Scholar 

  70. Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res. 2008;23(12):1923–34.

    Article  CAS  PubMed  Google Scholar 

  71. Christiansen C, Chesnut CH 3rd, Adachi JD, Brown JP, Fernandes CE, Kung AW, et al. Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord. 2010;11:130.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Silverman SL, Chines AA, Kendler DL, Kung AW, Teglbjærg CS, Felsenberg D, et al.; Bazedoxifene Study Group. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int. 2012;23(1):351–63.

    Google Scholar 

  73. de Villiers TJ, Chines AA, Palacios S, Lips P, Sawicki AZ, Levine AB, et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int. 2011;22(2):567–76.

    Article  CAS  PubMed  Google Scholar 

  74. Palacios S, Silverman SL, de Villiers TJ, Levine AB, Goemaere S, Brown JP, et al.; Bazedoxifene Study Group. A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: effects on bone density and fracture. Menopause. 2015;22(8):806–13.

    Article  PubMed  Google Scholar 

  75. Gallagher JC, Palacios S, Ryan KA, Yu CR, Pan K, Kendler DL, et al. Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials. Menopause. 2016;23(10):1083–91.

    Article  PubMed  Google Scholar 

  76. Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009;92(3):1045–52.

    Article  CAS  PubMed  Google Scholar 

  77. Pinkerton JV, Harvey JA, Lindsay R, Pan K, Chines AA, Mirkin S, et al.; SMART-5 Investigators. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. J Clin Endocrinol Metab. 2014;99(2):E189–98.

    Article  CAS  Google Scholar 

  78. Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992;326(13):852–6.

    Article  CAS  PubMed  Google Scholar 

  79. Love RR, Barden HS, Mazess RB, Epstein S, Chappell RJ. Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med. 1994;154(22):2585–8.

    Article  CAS  PubMed  Google Scholar 

  80. Henry NL, Nguyen A, Azzouz F, Li L, Robarge J, Philips S, Cao D, Skaar TC, Rae JM, Storniolo AM, Flockhart DA, Hayes DF, Stearns V. Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy. Br J Cancer. 2010;102(2):294–300.

    Article  CAS  PubMed  Google Scholar 

  81. Constantine GD, Kagan R, Miller PD. Effects of ospemifene on bone parameters including clinical biomarkers in postmenopausal women. Menopause. 2016;23(6):638–44.

    Article  PubMed  Google Scholar 

  82. Johnston SJ, Cheung KL. Fulvestrant – a novel endocrine therapy for breast cancer. Curr Med Chem. 2010;17(10):902–14.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic E18-A, Rochester, MN, USA

    Bart L. Clarke

Authors
  1. Bart L. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bart L. Clarke .

Editor information

Editors and Affiliations

  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

  2. Massachusetts General Hospital, Boston, MA, USA

    Marc N. Wein

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Clarke, B.L. (2020). Effects of Estrogens and SERMs on Bone Metabolism: Clinical Aspects. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-69287-6_12

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-319-69286-9

  • Online ISBN: 978-3-319-69287-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation