Lasofoxifene: Evidence of its therapeutic value in osteoporosis

References

• Anon. Osteoporosis Prevention, Diagnosis, and Therapy Consensus Statement 2000. JAMA. 2001;285:785–795.
   PubMed Web of Science ®Google Scholar
• Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? J Bone Miner Res. 1992;7:1005–1010.
   PubMed Web of Science ®Google Scholar
• Reginster JY, Burlet N. Osteoporosis: a still increasing prevalence. Bone. 2006;38:S4–S9.
   Web of Science ®Google Scholar
• Riggs BL, Melton III LJ. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone. 1995;17(5 Suppl):505S–511S.
   PubMed Web of Science ®Google Scholar
• Barrett-Connor E. The economic and human costs of osteoporotic fracture. Am J Med. 1995;98:3S–8S.
   PubMed Web of Science ®Google Scholar
• Melton LJ, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL. Vertebral fractures predict subsequent fracture. Osteoporos Int. 1999;10:214–221.
   PubMed Web of Science ®Google Scholar
• Anon. International Osteoporosis Foundation 1999. Survey by Helmut Minne, November 1999.
   Google Scholar
• Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–1767.
   PubMed Web of Science ®Google Scholar
• Cooper C, Campion G, Melton III LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2:285–289.
   PubMed Web of Science ®Google Scholar
• Black DM, Cummings SR, Genant HK, Nevitt MC, Palermo L, Browner W. Axial and appendicular bone density predict fractures in older women. J Bone Miner Res. 1992;7:633–638.
   PubMed Web of Science ®Google Scholar
• Cummings SR, Black DM, Nevitt MC, et al. Appendicular bone density and age predict hip fracture in women: the study of Osteoporotic Fractures Research Group. JAMA. 1990;263:665–668.
   PubMed Web of Science ®Google Scholar
• Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. Lancet. 1993;341:72–75.
   PubMed Web of Science ®Google Scholar
• Hui SL, Slemenda CW, Carey MA, Johnston CC. Choosing between predictors of fractures. J Bone Miner Res. 1995;10:1816–1822.
   PubMed Web of Science ®Google Scholar
• Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250–2261.
   PubMed Web of Science ®Google Scholar
• Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010–2018. Erratum: Lancet. 2006;368:28.
   PubMed Web of Science ®Google Scholar
• Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts and prospects. J Clin Invest. 2005;115:3318–3325.
   PubMed Web of Science ®Google Scholar
• Khosla S, Melton LJ III, Riggs BL. Clinical review 144: Estrogen and the male skeleton. J Clin Endocrinol Metab. 2002;87:1443–1450.
   PubMed Web of Science ®Google Scholar
• Gennari L, Khosla S, Bilezikian JP. Estrogen and fracture risk in men. J Bone Miner Res. 2008;23:1548–1551.
   PubMed Web of Science ®Google Scholar
• Riggs BL, Khosla S, Melton LJ III. Sex steroids and the construction and conservation of the adult skeleton. Endo Rev. 2002;23:279–302.
   PubMed Web of Science ®Google Scholar
• Green S, Walter P, Kumar V, Bornet J, Arpos P, Chambon P. Human estrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986;320:134–139.
   PubMed Web of Science ®Google Scholar
• Greene P, Gilna M, Waterfield A, Baker Y, Hort J, Shine, Sequence and expression of human estrogen receptor complementary DNA. Science. 1986;231:1150–1154.
   PubMed Web of Science ®Google Scholar
• Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996;93:5925–5930.
   PubMed Web of Science ®Google Scholar
• Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996;392:49–53.
   PubMed Web of Science ®Google Scholar
• Gustafsson JA. Estrogen receptor beta–a new dimension in estrogen mechanism of action. J Endocrinol. 1999;163:379–383.
   PubMed Web of Science ®Google Scholar
• Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab. 2001;86:2309–2314.
   PubMed Web of Science ®Google Scholar
• Ogawa S, Inoue S, Watanabe T, et al. The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitroiBiochem Biophys Res Commun. 1998;243:122–126.
   Google Scholar
• Riggs BL, Hartmann LC. Selective estrogen-receptor modulatorsmechanisms of action and application to clinical practice. N Engl J Med. 2003;348:618–629.
   PubMed Web of Science ®Google Scholar
• Pike AC. Lessons learnt from structural studies of the oestrogen receptor. Best Pract Res Clin Endocrinol Metab. 2006;20:1–14.
   PubMed Web of Science ®Google Scholar
• Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Women’s Health Initiative Investigators. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med. 2004;350:991–1004.
   PubMed Web of Science ®Google Scholar
• Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000;133:933–941.
   PubMed Web of Science ®Google Scholar
• Manson JE, Hsia J, Johnson KC, et al. Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–534.
   PubMed Web of Science ®Google Scholar
• Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465–1477.
   PubMed Web of Science ®Google Scholar
• Vassilopoulou-Sellin R. Breast cancer and hormonal replacement therapy. Ann N Y Acad Sci. 2003;997:341–350.
   PubMed Web of Science ®Google Scholar
• Anon. HRT: what are women (and their doctors) to do? Lancet. 2004;364:2069–2070.
   PubMed Web of Science ®Google Scholar
• Rabenda V, Mertens R, Fabri V, et al. Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporos Int. 2008;19:811–818.
   PubMed Web of Science ®Google Scholar
• Cho CH, Nuttall ME. Therapeutic potential of oestrogen receptor ligands in development for osteoporosis. Emerg Drugs. 2001;6:137–154.
   PubMedGoogle Scholar
• Nilsson S, Koehler KF. Oestrogen receptors and selective oestrogen receptor modulators: molecular and cellular pharmacology. Basic Clin Pharmacol Toxicol. 2005;96:15–25.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, De Paola V, Nuti R. Raloxifene in breast cancer prevention. Expert Opin Drug Saf. 2008;7:259–270.
   PubMed Web of Science ®Google Scholar
• Morello KC, Wurz GT, DeGregorio MW: SERMs: current status and future trends. Crc Crit Rev Oncol Hematol. 2002;43:63–76.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, Valleggi F, Martini G, Nuti R. Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. Drugs Aging. 2007;24:361–379.
   PubMed Web of Science ®Google Scholar
• Delmas PD, Bjarnason NH, Mitlak BH, 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.
   PubMed Web of Science ®Google Scholar
• Lufkin EG, Whitaker MD, Nickelsen T, et al. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res. 1998;13:1747–1754.
   PubMed Web of Science ®Google Scholar
• Ettinger B, Black DM, Mitlak BH, 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;282:637–645. Erratum: JAMA. 1999;282:2124.
   PubMed Web of Science ®Google Scholar
• Bryant HU, Glasebrook AL, Yang NN, Sato M. A pharmacological review of raloxifene. J Bone Miner Metab. 1996;14:1–9.
   Google Scholar
• Weinstein RS, Parfitt AM, Marcus R, Greenwald M, Crans G, Muchmore DB. Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women. Osteoporos Int. 2003;14:814–822.
   PubMed Web of Science ®Google Scholar
• Prestwood KM, Gunness M, Muchmore DB, Lu Y, Wong M, Raisz LG. A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab. 2000;85:2197–2202.
   PubMed Web of Science ®Google Scholar
• Rosati RL, Da Silva Jardine P, Cameron KO. Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene. J Med Chem. 1998;41:2928–2931.
   PubMed Web of Science ®Google Scholar
• Yang X, Reinhold AR, Rosati RL, Liu KK. Enzyme-catalyzed asymmetric deacylation for the preparation of lasofoxifene (CP-336156), a selective estrogen receptor modulator. Org Lett. 2000;2:4025–4027.
   PubMed Web of Science ®Google Scholar
• Cameron K. Discovery of CP-336156, a potent estrogen agonist. San Francisco, CA: 219th ACS Nat Meeting; 2000. (MEDI 326).
   Google Scholar
• Gennari L. Lasofoxifene (Pfizer). Curr Opin Investig Drugs. 2005;6:1067–1078.
   PubMedGoogle Scholar
• Gennari L. Lasofoxifene: a new type of selective estrogen receptor modulator for the treatment of osteoporosis. Drugs Today (Barc). 2006;42:355–367.
   PubMed Web of Science ®Google Scholar
• Gennari L, Merlotti D, Martini G, Nuti R. Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis. Expert Opin Investig Drugs. 2006;15:1091–1103.
   PubMed Web of Science ®Google Scholar
• Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet. 2003;42:361–372.
   PubMed Web of Science ®Google Scholar
• Katzenellenbogen JA. D- 1, 2-Dyaril-3,4-dihydronaphthalenes: photofluorogenic ligands for the estrogen receptor. J Steroid Biochem. 1985;23:929–937.
   PubMedGoogle Scholar
• Jhonson KA, Gardner MJ, Prakash C. In vivo and in vitro metabolites of a next-generation selective estrogen receptor modulator, lasofoxifene, in humans. Drug Metab Rev. 2004;36:246.
   Web of Science ®Google Scholar
• Gardner M, Nishizawa Y, Wei G, Dogolo L, Calcagni A. A single-dose pharmacokinetic study of lasofoxifene in Japanese and Caucasian postmenopausal women [abstract]. J Bone Miner Res. 2004;19:M469.
   Google Scholar
• Gardner M, Taylor A, Wei G, Calcagni A Jr, Duncan B, Milton A. Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women. J Clin Pharmacol. 2006;46:52–58.
   PubMed Web of Science ®Google Scholar
• Roman D, Bramson C, Ouellet D, Randinitis E, Gardner M. Effect of lasofoxifene on the pharmacokinetics of digoxin in healthy postmenopausal women. J Clin Pharmacol. 2005;45:1407–1412.
   PubMed Web of Science ®Google Scholar
• Moller RA, Fisher JM, Taylor AE, et al. Effects of steady-state lasofoxifene on CYP2D6- and CYP2E1-mediated metabolism. Ann Pharmacother. 2006;40:32–37.
   PubMed Web of Science ®Google Scholar
• Bramson C, Ouellet D, Roman D, Randinitis E, Gardner MJ. A singledose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment. J Clin Pharmacol. 2006;46:29–36.
   PubMed Web of Science ®Google Scholar
• Ke HZ, Paralkar VM, Grasser WA. Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models. Endocrinology. 1998;139:2068–2076.
   PubMed Web of Science ®Google Scholar
• Ke HZ, Qi H, Chidsey-Frink KL, et al. Effects of different dose regimens of lasofoxifene (CP-336,156) in preventing bone loss in ovariectomized rats. J Bone Miner Res. 2000;15:S1–S310.
   Web of Science ®Google Scholar
• Ke HZ, Foley GL, Simmons HA, Shen V, Thompson DD. Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats. Endocrinology. 2004;145:1996–2005.
   PubMed Web of Science ®Google Scholar
• Ke HZ, Qi H, Crawford DT, et al. Lasofoxifene (CP-336-156), a selective estrogen receptor modulator, prevents bone loss induced by aging and orchidectomy in the adult rat. Endocrinology. 2000;141: 1338–1344.
   PubMed Web of Science ®Google Scholar
• Ke HZ, Oi H, Chidsey-Frink KL, et al. 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.
   PubMed Web of Science ®Google Scholar
• Kharode YP, Green PD, Marzolf JT, et al. Comparison of the effects of bazedoxifene, raloxifene, lasofoxifene and risedronate, co-treatment on h-PTH-induced reversal of established osteopenia in ovariectomized rats [abstract]. J Bone Miner Res. 2003;18:S273, SU387.
   Web of Science ®Google Scholar
• Cohen LA, Pittman B, Wang CX, et al. LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model. Cancer Res. 2001;61:8683–8688.
   PubMed Web of Science ®Google Scholar
• Chesworth R, Zawistoski MP, Lefker BA, et al. Tetrahydroisoquinolines as subtype selective estrogen agonists/antagonists. Bioorg Med Chem Letters. 2004;14:2729–2733.
   PubMed Web of Science ®Google Scholar
• Cappon GD, Horimoto M, Hurtt ME. Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats. Birth Defects Res B Dev Reprod Toxicol. 2004;71: 142–149.
   PubMed Web of Science ®Google Scholar
• Terry KK, Cappon GD, Hurtt ME, Tassinari MS, Gupta U. Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in female rats. Birth Defects Res B Dev Reprod Toxicol. 2004;71:150–160.
   PubMed Web of Science ®Google Scholar
• Weisenburger WP, Hagler AR, Tassinari MS. Pre- and postnatal development studies of lasofoxifene, a selective estrogen receptor modulator (SERM), in Sprague-Dawley rats. Birth Defects Res B Dev Reprod Toxicol. 2004;71:171–184.
   PubMed Web of Science ®Google Scholar
• Ozolins TRS, Gupta U. Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits. Birth Defects Res B Dev Reprod Toxicol. 2004;71: 161–170.
   PubMed Web of Science ®Google Scholar
• Cohen IR, Wierda D, Griffey KI, Fisher LF, Francis Pc. The selective estrogen receptor modulator, raloxifene: a segment II/III delivery study in rats. Reprod Toxicol. 1998;12:271–288.
   PubMed Web of Science ®Google Scholar
• McClung MR, Siris E, Cummings S, et al. Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene. Menopause. 2006;13:377–386.
   PubMed Web of Science ®Google Scholar
• Anon. Background document for meeting of Advisory Committee for Reproductive Health Drugs. NDA 22–242. Lasofoxifene Tartrate (Proposed trade name: FABLYN). September 8, 2008. Accessed on Dec 10, 2008. Available from: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4381b1-01-FDA.pdf.
   Google Scholar
• Anon. Fablyn® (lasofoxifene tartrate) 0.5 mg tablets NDA 22–242. Reproductive Health Drugs Advisory Committee briefing document. September 8, 2008. Accessed on Dec 10, 2008. Available at http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4381b1-02-Pfizer.pdf.
   Google Scholar
• Moller R, Fisher J, Taylor A, Kolluri S, Gardner M. Effect of food on the pharmacokinetics of lasofoxifene in healthy postmenopausal women [abstract]. J Bone Miner Res. 2004;19:SU487.
   Google Scholar
• Lee A, Radecki D, Wolter K, et al. Lasofoxifene phase 2 and phase 3 clinical trial design and strategy [abstract]. J Bone Miner Res. 2005;20:M384.
   Google Scholar
• Day W, Martel J, Lee A. Lasofoxifene phase 2 dose response analysis in postmenopausal women [abstract]. J Bone Miner Res. 2005;20:M385.
   Google Scholar
• Moffett AH, Ettinger M, Bolognese M, et al. Lasofoxifene, a next generation SERM, is effective in preventing loss of BMD and reducing LDL-C in postmenopausal women [abstract]. J Bone Miner Res. 2004;19:SA426.
   Google Scholar
• Portman DJ, Moffett AH, Bachman GA, West C, Symons J. Lasofoxifene, a selective estrogen receptor modulator, improves objective measures of vaginal atrophy. Obstet Gynecol. 2004;103: 25S–26S.
   Web of Science ®Google Scholar
• Ettinger M, Schwartz E, Emkey R, et al. Lasofoxifene: a next generation selective estrogen receptor modulator (SERM) in the prevention of bone loss in postmenopausal women. New Orleans, LA: Presented at the 86th Annual Meeting of the Endocrine Society; June 16–19, 2004.
   Google Scholar
• Anon. Ligand earns milestone from Pfizer as lasofoxifene enters phase II for osteoporosis; first of three late-stage SERM products advancing prospects of future royalties. San Diego, CA: Ligand Pharmaceuticals International Inc; 2000.
   Google Scholar
• McClung M, Omizo M, Weiss S, et al. Comparison of lasofoxifene and raloxifene for the prevention of bone loss in postmenopausal women [abstract]. J Bone Miner Res. 2004;19:SA424.
   Web of Science ®Google Scholar
• McClung M, Portman D, Emkey R, et al. Comparison of the extraskeletal effects of lasofoxifene and raloxifene [abstract]. J Bone Miner Res. 2004;19:SA423.
   Google Scholar
• McClung M, Siris E, Cummings S, et al. Lasofoxifene increased BMD of the spine and hip and decreased bone turnover markers in postmenopausal women with low or normal BMD [abstract]. J Bone Miner Res. 2005;20:F429.
   Web of Science ®Google Scholar
• Davidson M, Moffett A, Welty F, et al. Extraskeletal effects of lasofoxifene on postmenopausal women [abstract]. J Bone Miner Res. 2005;20: SA428.
   Web of Science ®Google Scholar
• Eastell R, Reid DM, Vukicevic S, et al. The effects of lasofoxifene on bone turnover markers: the PEARL trial [abstract]. J Bone Miner Res. 2008;23:1287.
   PubMed Web of Science ®Google Scholar
• Glover SJ, Rogers A, Gossiel F, Eastell R. A randomized double blinded controlled trial of individual response in biochemical markers of bone turnover to lasofoxifene therapy [abstract]. J Bone Miner Res. 2008; 23:M507.
   Google Scholar
• Cummings SR, Eastell R, Ensrud K, et al. The effects of lasofoxifene on fractures and breast cancer: 3-year results from the PEARL trial [abstract]. J Bone Miner Res. 2008;23:1288.
   Web of Science ®Google Scholar
• Goldstein SR. Not all SERMs are created equal. Menopause. 2006;13:325–327.
   PubMed Web of Science ®Google Scholar
• Wang XN, Simmons HA, Salatto CT, Cosgrove PG, Thompson DD. Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor beta and androgen receptor in rats. Menopause. 2006;13:609–620.
   PubMed Web of Science ®Google Scholar
• Fleurence RL, Iglesias CP, Torgerson DJ. Economic evaluations of interventions for the prevention and treatment of osteoporosis: a structured review of the literature. Osteoporos Int. 2006;17:29–40.
   PubMed Web of Science ®Google Scholar
• Fleurence RL, Iglesias CP, Johnson JM. The cost effectiveness of bisphosphonates for the prevention and treatment of osteoporosis: a structured review of the literature. Pharmacoeconomics. 2007;25: 913–933.
   PubMed Web of Science ®Google Scholar
• Tosteson NA, Burge RT, Marshall DA, Lindsay R. Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations. Am J Manag Care. 2008;14:605–615.
   PubMed Web of Science ®Google Scholar
• Tosteson NA, Melton LJ, Dawson-Hughes B, et al. Cost-effective osteoporosis treatment thresholds: The United States perspective. Osteopros Int. 2008;19:437–447.
   PubMed Web of Science ®Google Scholar
• Stevenson N, Jones ML, De Nigris E, Brewer N, Davis S, Oakley J. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess. 2005;9:1–160.
   PubMed Web of Science ®Google Scholar
• Cauley JA, Norton L, Lippman ME, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat. 2001;65:125–134. Correction: Breast Cancer Res Treat. 2001; 67.
   PubMed Web of Science ®Google Scholar
• Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96:1751–1761.
   PubMed Web of Science ®Google Scholar