Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats

Bone

Volumn 49, Issue 3, 2011, Pages 376-386

  Komm, Barry S ^a   Vlasseros, Fay ^b   Samadfam, Rana ^b   Chouinard, Luc ^b   Smith, Susan Y ^b  

^a PFIZER INC   (United States)

^b CHARLES RIVER LABORATORIES   (United States)

Author keywords

Bazedoxifene; BZA CE; Conjugated estrogens; SERM; Tissue selective estrogen complex; TSEC

Indexed keywords

BAZEDOXIFENE; CHOLESTEROL; CONJUGATED ESTROGEN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOCHEMISTRY; BONE DENSITY; BONE MASS; BONE STRENGTH; BONE STRUCTURE; BONE TURNOVER; CANCELLOUS BONE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORTICAL BONE; DRUG EFFECT; FEMALE; FEMUR; LUMBAR SPINE; LUMBAR VERTEBRA; MONOTHERAPY; NONHUMAN; OVARIECTOMY; RAT; TIBIA; TREATMENT DURATION; UTERUS WEIGHT;

ANIMALS; BIOLOGICAL MARKERS; BONE AND BONES; BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; ESTROGENS; ESTROGENS, CONJUGATED (USP); FEMALE; FEMUR; HUMANS; INDOLES; LUMBAR VERTEBRAE; ORGAN SIZE; OVARIECTOMY; RATS; RATS, SPRAGUE-DAWLEY; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TIBIA; UTERUS;

EID: 79960580689     PISSN: 87563282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bone.2011.05.024     Document Type: Article

References (58)

1. Freeman E.W., Sammel M.D., Lin H., Gracia C.R., Kapoor S. Symptoms in the menopausal transition: hormone and behavioral correlates. Obstet Gynecol 2008, 111:127-136.
2. Lobo R.A., Whitehead M.I. Is low-dose hormone replacement therapy for postmenopausal women efficacious and desirable?. Climacteric 2001, 4:110-119.
3. Constantine G.D., Pickar J.H. Estrogens in postmenopausal women: recent insights. Curr Opin Pharmacol 2003, 3:626-634.
4. Jackson R.D., Wactawski-Wende J., LaCroix A.Z., Pettinger M., Yood R.A., Watts N.B., et al. Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial. J Bone Miner Res 2006, 21:817-828.
5. Lindsay R., Gallagher J.C., Kleerekoper M., Pickar J.H. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002, 287:2668-2676.
6. Suckling J., Lethaby A., Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2006, (4). (CD001500).
7. MacLennan A.H., Broadbent J.L., Lester S., Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004, (4). (CD002978).
8. Lindsay R., Gallagher J.C., Kleerekoper M., Pickar J.H. Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women. Osteoporos Int 2005, 16:372-379.
9. Anderson G.L., Limacher M., Assaf A.R., Bassford T., Beresford S.A., Black H., et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004, 291:1701-1712.
10. Gambacciani M., Vacca F. Postmenopausal osteoporosis and hormone replacement therapy. Minerva Med 2004, 95:507-520.
11. Greendale G.A., Wells B., Marcus R., Barrett-Connor E. How many women lose bone mineral density while taking hormone replacement therapy? Results from the Postmenopausal Estrogen/Progestin Interventions Trial. Arch Intern Med 2000, 160:3065-3071.
12. Cauley J.A., Robbins J., Chen Z., Cummings S.R., Jackson R.D., LaCroix A.Z., et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003, 290:1729-1738.
13. Lobo R.A., Bush T., Carr B.R., Pickar J.H. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril 2001, 76:13-24.
14. Espeland M.A., Marcovina S.M., Miller V., Wood P.D., Wasilauskas C., Sherwin R., et al. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Circulation 1998, 97:979-986.
15. Tannen R.L., Weiner M.G., Xie D., Barnhart K. Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy. Hum Reprod 2007, 22:1769-1777.
16. Riggs B.L., Hartmann L.C. Selective estrogen-receptor modulators - mechanisms of action and application to clinical practice. N Engl J Med 2003, 348:618-629.
17. McDonnell D.P., Connor C.E., Wijayaratne A., Chang C.Y., Norris J.D. Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators. Recent Prog Horm Res 2002, 57:295-316.
18. Palacios S. The future of the new selective estrogen receptor modulators. Menopause Int 2007, 13:27-34.
19. Komm B.S., Lyttle C.R. Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann N Y Acad Sci 2001, 949:317-326.
20. Taylor H.S. Designing the ideal selective estrogen receptor modulator-an achievable goal?. Menopause 2009, 16:609-615.
21. Arun B., Anthony M., Dunn B. The search for the ideal SERM. Expert Opin Pharmacother 2002, 3:681-691.
22. Kharode Y., Bodine P.V., Miller C.P., Lyttle C.R., Komm B.S. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008, 149:6084-6091.
23. Komm B.S. A new approach to menopausal therapy: the tissue selective estrogen complex. Reprod Sci 2008, 15:984-992.
24. North American Menopause Society Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010, 17:242-255.
25. Archer D.F. Tissue-selective estrogen complexes: a promising option for the comprehensive management of menopausal symptoms. Drugs Aging 2010, 27:533-544.
26. Komm B.S., Kharode Y.P., Bodine P.V., Harris H.A., Miller C.P., Lyttle C.R. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005, 146:3999-4008.
27. Miller P.D., Chines A.A., Christiansen C., Hoeck H.C., Kendler D.L., Lewiecki E.M., 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, 23:525-535.
28. Silverman S.L., Christiansen C., Genant H.K., Vukicevic S., Zanchetta J.R., de Villiers T.J., 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, 23:1923-1934.
29. Peano B.J., Crabtree J.S., Komm B.S., Winneker R.C., Harris H.A. Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 2009, 150:1897-1903.
30. Parfitt A.M., Drezner M.K., Glorieux F.H., Kanis J.A., Malluche H., Meunier P.J., et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 1987, 2:595-610.
31. Albright F., Smith P.H., Richardson A.M. Postmenopausal osteoporosis: its clinical features. JAMA 1941, 116:2465-2474.
32. Delmas P.D., Bjarnason N.H., Mitlak B.H., Ravoux A.C., Shah A.S., Huster W.J., et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997, 337:1641-1647.
33. Ettinger B., Black D.M., Mitlak B.H., Knickerbocker R.K., Nickelsen T., Genant H.K., et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999, 282:637-645. for the Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.
34. Jordan V.C., Phelps E., Lindgren J.U. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 1987, 10:31-35.
35. Lerner L.J., Jordan V.C. Development of antiestrogens and their use in breast cancer: eighth Cain memorial award lecture. Cancer Res 1990, 50:4177-4189.
36. Love R.R., Mazess R.B., Barden H.S., Epstein S., Newcomb P.A., Jordan V.C., et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992, 326:852-856.
37. Early Breast Cancer Trialists' Collaborative Group Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998, 351:1451-1467.
38. Fisher B., Dignam J., Wolmark N., Wickerham D.L., Fisher E.R., Mamounas E., et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 1999, 353:1993-2000.
39. Prestwood K.M., Kenny A.M., Kleppinger A., Kulldorff M. Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. JAMA 2003, 290:1042-1048.
40. Grady D., Ettinger B., Moscarelli E., Plouffe L., Sarkar S., Ciaccia A., et al. Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol 2004, 104:837-844.
41. Lethaby A., Suckling J., Barlow D., Farquhar C.M., Jepson R.G., Roberts H. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004, (3). (CD000402).
42. Glusman J.E., Huster W.J., Paul S. Raloxifene effects on vasomotor and other climacteric symptoms in postmenopausal women. Prim Care Update Ob Gyns 1998, 5:166.
43. Gennari L., Merlotti D., Valleggi F., Nuti R. Ospemifene use in postmenopausal women. Expert Opin Investig Drugs 2009, 18:839-849.
44. Komm B.S., Kharode Y., Bodine P., et al. Bazedoxifene+conjugated estrogens: a balanced combination to provide optimal "estrogenic" safety and efficacy. J Bone Miner Metab 2003, 18:s272.
45. Sato M., Turner C.H., Wang T., Adrian M.D., Rowley E., Bryant H.U. LY353381.HCl: a novel raloxifene analog with improved SERM potency and efficacy in vivo. J Pharmacol Exp Ther 1998, 287:1-7.
46. Gaspard U.J., Gottal J.M., van den Brule F.A. Postmenopausal changes of lipid and glucose metabolism: a review of their main aspects. Maturitas 1995, 21:171-178.
47. Draper M.W., Flowers D.E., Huster W.J., Neild J.A., Harper K.D., Arnaud C. A controlled trial of raloxifene (LY139481) HCl: impact on bone turnover and serum lipid profile in healthy postmenopausal women. J Bone Miner Res 1996, 11:835-842.
48. Evans G.L., Bryant H.U., Magee D.E., Turner R.T. Raloxifene inhibits bone turnover and prevents further cancellous bone loss in adult ovariectomized rats with established osteopenia. Endocrinology 1996, 137:4139-4144.
49. Ke H.Z., Qi H., Chidsey-Frink K.L., Crawford D.T., Thompson D.D. Lasofoxifene (CP-336,156) protects against the age-related changes in bone mass, bone strength, and total serum cholesterol in intact aged male rats. J Bone Miner Res 2001, 16:765-773.
50. Kharode Y.P., Bodine P.V., Bex F.J., Komm B.S. Skeletal and uterine effects of bazedoxifene in ovariectomized mice and rats with comparison to raloxifene and lasofoxifene. Fertil Steril 2006, 86:S91. (Abstract O-213).
51. Parton M., Smith I.E. Controversies in the management of patients with breast cancer: adjuvant endocrine therapy in premenopausal women. J Clin Oncol 2008, 26:745-752.
52. DuSell C.D., Nelson E.R., Wittmann B.M., Fretz J.A., Kazmin D., Thomas R.S., et al. Regulation of aryl hydrocarbon receptor function by selective estrogen receptor modulators. Mol Endocrinol 2009, 24:33-46.
53. Baylink D.J., Bernstein D.S. The effects of fluoride therapy on metabolic bone disease. A histologic study. Clin Orthop Relat Res 1967, 55:51-85.
54. Lueg M.C. Postmenopausal osteoporosis: treatment with low-dose sodium fluoride and estrogen. South Med J 1988, 81:597-600.
55. Reich T., Gefen A. Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur. Biomed Eng Online 2006, 5:45.
56. Lindsay R., Gallagher J.C., Kagan R., Pickar J.H., Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009, 92:1045-1052.
57. Ronkin S., Northington R., Baracat E., Nunes M.G., Archer D.F., Constantine G., et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005, 105:1397-1404.
58. Stovall D.W., Utian W.H., Gass M.L., Qu Y., Muram D., Wong M., et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause 2007, 14:510-517.