title: SERMs and SERMs with estrogen for postmenopausal osteoporosis.
abstract: Bone loss with aging places postmenopausal women at a higher risk for osteoporosis and its consequences such as fractures, pain, disability, and increased morbidity and mortality. Approximately 200 million patients worldwide are affected. The Third National Health and Nutrition Examination Survey (NHANES III) estimated that up to 18% of US women aged 50 and older have osteoporosis and up to 50% have osteopenia. Greater than 2 million osteoporotic related fractures occurred in the United States with direct healthcare costs exceeding $17 billion. Hormone Replacement Therapy (HRT) was a popular option for postmenopausal women before the Women's Health Initiative (WHI). Several agents are available in the U.S., including bisphosphonates, hormone therapy, calcitonin, parathyroid hormone and the selective estrogen receptor modulator (SERM) raloxifene. There are concerns about long term safety and compliance. Therefore, other agents are under investigation. SERMs are a diverse group of agents that bind to the estrogen receptor and each SERM appears to have a unique set of clinical responses, which are not always consistent with the typical responses seen with other SERMs. This article will discuss the SERMs approved in the United States, tamoxifene and raloxifene, and investigational SERMs. The ideal SERM would include the beneficial effects of estrogen in bone, heart and the central nervous system, with neutral or antagonistic effects in tissues where estrogen effects are undesirable(breast and endometrium). A new target in treating postmenopausal osteoporosis is the tissue estrogen complex or the pairing of a SERM with a conjugated estrogen known as a tissue selective estrogen complex (TSEC). This novel approach is currently being evaluated with bazodoxifene which could yield the beneficial effects of estrogens and SERMS, while potentially being more tolerable and safer than either therapy alone.
authors.affiliation: Bethesda Health Research, Bethesda, MD, USA. mbolognese@erols.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bolognese
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators
references.citation: Obstet Gynecol. 2005 Jun;105(6):1397-404
references.pmid: 15932835
references.citation: J Clin Pharmacol. 2006 Jan;46(1):52-8
references.pmid: 16397284
references.citation: Endocrinology. 2008 Dec;149(12):6084-91
references.pmid: 18703623
references.citation: J Bone Miner Res. 2008 Apr;23(4):525-35
references.pmid: 18072873
references.citation: Breast Cancer Res Treat. 2002 May;73(2):161-75
references.pmid: 12088118
references.citation: Clin Biomech (Bristol, Avon). 2002 Feb;17(2):81-8
references.pmid: 11832257
references.citation: Menopause. 2003 Jul-Aug;10(4):337-44
references.pmid: 12851517
references.citation: Breast Cancer Res Treat. 2001 Jan;65(2):125-34
references.pmid: 11261828
references.citation: Curr Med Res Opin. 2005 Sep;21(9):1441-52
references.pmid: 16197663
references.citation: J Bone Miner Res. 2007 Mar;22(3):465-75
references.pmid: 17144789
references.citation: JAMA. 1999 Jun 16;281(23):2189-97
references.pmid: 10376571
references.citation: Fertil Steril. 2009 Sep;92(3):1045-1052
references.pmid: 19635616
references.citation: Am J Cardiol. 2006 Feb 15;97(4):520-7
references.pmid: 16461049
references.citation: Obstet Gynecol. 2001 Jul;98(1):91-6
references.pmid: 11430963
references.citation: Arch Intern Med. 2000 Dec 11-25;160(22):3444-50
references.pmid: 11112238
references.citation: JAMA. 1999 Aug 18;282(7):637-45
references.pmid: 10517716
references.citation: JAMA. 2006 Jun 21;295(23):2727-41
references.pmid: 16754727
references.citation: J Natl Cancer Inst. 2004 Dec 1;96(23):1751-61
references.pmid: 15572757
references.citation: N Engl J Med. 2010 Feb 25;362(8):686-96
references.pmid: 20181970
references.citation: N Engl J Med. 2006 Jul 13;355(2):125-37
references.pmid: 16837676
references.citation: Obstet Gynecol. 2004 Oct;104(4):837-44
references.pmid: 15458908
references.citation: Curr Top Med Chem. 2006;6(3):181-202
references.pmid: 16515478
references.citation: Menopause. 2005 Jul-Aug;12(4):444-52
references.pmid: 16037760
references.citation: Menopause. 2006 May-Jun;13(3):377-86
references.pmid: 16735934
references.citation: J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88
references.pmid: 9747868
references.citation: Arch Intern Med. 2004 May 24;164(10):1108-12
references.pmid: 15159268
references.citation: Fertil Steril. 2009 Sep;92(3):1039-1044
references.pmid: 19635614
references.citation: Arch Intern Med. 1991 Sep;151(9):1842-7
references.pmid: 1888251
references.citation: J Bone Miner Res. 2005 Sep;20(9):1514-24
references.pmid: 16059623
references.citation: Obstet Gynecol. 1999 Apr;93(4):558-65
references.pmid: 10214833
references.citation: Bone. 2009 May;44(5):734-43
references.pmid: 19195497
references.citation: Reprod Sci. 2008 Dec;15(10):984-92
references.pmid: 19088368
references.citation: N Engl J Med. 1997 Dec 4;337(23):1641-7
references.pmid: 9385122
references.citation: Am J Obstet Gynecol. 1997 Dec;177(6):1458-64
references.pmid: 9423751
references.citation: J Ultrasound Med. 1999 Jul;18(7):503-12
references.pmid: 10400054
references.citation: Obstet Gynecol Surv. 2008 Mar;63(3):163-81
references.pmid: 18279543
references.citation: Fertil Steril. 2009 Sep;92(3):1025-1038
references.pmid: 19635615
references.citation: J Bone Miner Res. 1997 Nov;12(11):1761-8
references.pmid: 9383679
references.citation: Acta Obstet Gynecol Scand. 2006;85(2):135-42
references.pmid: 16532904
references.citation: Lancet. 2000 Mar 4;355(9206):848-9
references.pmid: 10711957
references.citation: Climacteric. 2005 Sep;8(3):214-20
references.pmid: 16390753
references.citation: Am J Psychiatry. 2005 Apr;162(4):683-90
references.pmid: 15800139
references.citation: Menopause. 1999 Fall;6(3):188-95
references.pmid: 10486787
references.citation: Arch Intern Med. 2004 Apr 26;164(8):871-9
references.pmid: 15111373
references.citation: Gynecol Oncol. 2002 May;85(2):388-90
references.pmid: 11972407
references.citation: Fertil Steril. 2009 Sep;92(3):1018-1024
references.pmid: 19635613
references.citation: Menopause. 2005 Mar;12(2):160-4
references.pmid: 15772563
references.citation: Drugs. 2006;66(2):191-221
references.pmid: 16451093
references.citation: J Bone Miner Res. 1996 Jun;11(6):835-42
references.pmid: 8725181
references.citation: Maturitas. 2005 Oct 16;52(2):87-101
references.pmid: 15967604
references.citation: Obstet Gynecol. 2004 Feb;103(2):261-6
references.pmid: 14754693
references.citation: Endocrinology. 2005 Sep;146(9):3999-4008
references.pmid: 15961563
references.citation: N Engl J Med. 2001 Apr 19;344(16):1207-13
references.pmid: 11309635