title: Lasofoxifene: selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis.
abstract: OBJECTIVE
  To review literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of lasofoxifene (CP-336156), a selective estrogen receptor modulator (SERM) that is not approved for use in the US.
  
  
  METHODS
  Literature was accessed through the MEDLINE and EMBASE databases (1985-June 2010) using the terms lasofoxifene and selective estrogen receptor modulators. Reference lists from retrieved articles were also manually reviewed. The Food and Drug Administration and Pfizer provided additional information.
  
  
  METHODS
  All clinical trials evaluating lasofoxifene were included in this review. In addition, all articles evaluating the pharmacology, pharmacokinetics, and safety of lasofoxifene in humans were reviewed.
  
  
  RESULTS
  Lasofoxifene is a third-generation SERM with markedly higher in vitro and in vivo potency and oral bioavailability than other SERMs. The drug has produced significant improvements in bone density and biochemical markers of bone turnover in preclinical studies and in Phase 2 and 3 clinical trials. In these trials, lasofoxifene has shown a favorable safety profile, with adverse events including hot flushes, leg cramps, and increased vaginal moisture. One 2-year major comparative study in postmenopausal women determined that lasofoxifene and raloxifene were equally effective at increasing total hip bone mineral density (BMD), while lasofoxifene had a significantly greater effect on lumbar spine BMD.
  
  
  CONCLUSIONS
  Osteoporosis is a significant health problem. While the results of further clinical trials are needed to define the risks and benefits of treatment, particularly relating to fractures, lasofoxifene may prove to be an effective and well-tolerated therapeutic option for the prevention of bone loss in postmenopausal women.
authors.affiliation: School of Pharmacy, University of Tasmania, Tasmania, Australia. G.Peterson@utas.edu.au
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Peterson
authors.forename: Mark
authors.initials: M
authors.lastname: Naunton
authors.forename: Lisette K
authors.initials: LK
authors.lastname: Tichelaar
authors.forename: Luigi
authors.initials: L
authors.lastname: Gennari
mesh_terms: D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; C111332:Lasofoxifene