title: Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women.
abstract: BACKGROUND
  In contrast to nonsteroidal aromatase inhibitors, the steroidal aromatase inactivator exemestane does not have detrimental effects on bone in animal models. This study was designed to compare the effects of exemestane with the nonsteroidal aromatase inhibitors anastrozole and letrozole on serum and urine levels of biomarkers of bone turnover in healthy postmenopausal women.
  
  
  METHODS
  Changes in the concentrations of bone-turnover markers, estrogens, and lipids were assessed after daily administration of exemestane (25 mg), letrozole (2.5 mg), anastrozole (1 mg), or placebo for 24 weeks in healthy postmenopausal women. The primary end point was the percentage change from baseline in bone-turnover-marker levels at week 24. The baseline-adjusted area under the curve (AUC) for weeks 0-12 and 0-24 was calculated to evaluate changes in bone turnover over time, rather than at discrete time points.
  
  
  RESULTS
  Seventy-four (88%) of 84 randomized subjects were evaluable for bone-marker assays. Reductions in plasma estrogen levels and increases in bone-resorption markers were comparable for each aromatase inhibitor. Uniquely, exemestane consistently increased the percentage change from baseline in the level of serum procollagen type I N-terminal propeptide (PINP), a marker of bone formation, at week 24. In the active-treatment groups, the baseline-adjusted AUC at weeks 0-12 and 0-24 for PINP was significantly greater for exemestane than the other aromatase inhibitors.
  
  
  CONCLUSIONS
  Exemestane increased serum levels of the bone-formation marker PINP after 24 weeks, suggesting a specific bone-formation effect related to its androgenic structure. Potential effects on cortical bone and reduced fracture risk must be verified in a comparative clinical trial.
authors: Massachusetts General Hospital, 55 Fruit Street, LRH 302, Boston, MA 02114, USA. pgoss@partners.org
authors: Paul E
authors: PE
authors: Goss
authors: Peyman
authors: P
authors: Hadji
authors: Milayna
authors: M
authors: Subar
authors: Paula
authors: P
authors: Abreu
authors: Torben
authors: T
authors: Thomsen
authors: Jose
authors: J
authors: Banke-Bochita
mesh_terms: D000368:Aged; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood*; D008593:Menopause; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D010446:Peptide Fragments / Q000097:blood; D010919:Placebos; D011347:Procollagen / Q000097:blood; D016037:Single-Blind Method; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D015415:Biomarkers; D004967:Estrogens; D008055:Lipids; D009570:Nitriles; D010446:Peptide Fragments; D010919:Placebos; D011347:Procollagen; D014230:Triazoles; C047202:procollagen Type I N-terminal peptide; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane
references: Eur J Cancer. 2006 May;42(8):1044-51
references: 16554149
references: J Clin Oncol. 2005 Dec 20;23(36):9433-4; author reply 9433-5
references: 16361646
references: Eur J Cancer. 2006 Nov;42(17):2968-75
references: 16963261
references: Breast Cancer Res Treat. 1999 Sep;57(2):183-92
references: 10598045
references: Endocr Relat Cancer. 1999 Jun;6(2):325-32
references: 10731126
references: Physiol Rev. 2001 Jan;81(1):419-447
references: 11152762
references: J Clin Endocrinol Metab. 2001 Mar;86(3):957-64
references: 11238469
references: J Steroid Biochem Mol Biol. 2001 Jan-Mar;76(1-5):199-202
references: 11384878
references: Fertil Steril. 2002 Apr;77 Suppl 4:S34-41
references: 12007900
references: Lancet. 2002 Jun 22;359(9324):2131-9
references: 12090977
references: Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):614-21
references: 12101108
references: Clin Lab. 2002;48(7-8):407-13
references: 12146575
references: J Br Menopause Soc. 2003 Mar;9(1):10-5
references: 12804307
references: Cancer. 2003 Nov 1;98(9):1802-10
references: 14584060
references: N Engl J Med. 2003 Nov 6;349(19):1793-802
references: 14551341
references: Bone. 2004 Mar;34(3):384-92
references: 15003786
references: N Engl J Med. 2004 Mar 11;350(11):1081-92
references: 15014181
references: Curr Med Res Opin. 2004 Mar;20(3):341-9
references: 15025843
references: Mayo Clin Proc. 2004 Apr;79(4 Suppl):S14-8
references: 15065633
references: Clin Cancer Res. 2004 Sep 1;10(17):5717-23
references: 15355898
references: Clin Chem. 1993 Apr;39(4):561-77
references: 8472349
references: J Clin Invest. 1996 Jan 1;97(1):14-21
references: 8550826
references: J Clin Endocrinol Metab. 1996 Jan;81(1):37-43
references: 8550780
references: Obstet Gynecol. 1996 Mar;87(3):350-4
references: 8598953
references: J Bone Miner Res. 1997 Sep;12(9):1416-23
references: 9286757
references: Clin Cancer Res. 1997 Jul;3(7):1101-8
references: 9815789
references: Lancet. 2005 Jan 1-7;365(9453):60-2
references: 15639680
references: J Clin Oncol. 2005 Jan 20;23(3):619-29
references: 15545664
references: Clin Ther. 2005 Jan;27(1):1-11
references: 15763602
references: J Clin Oncol. 2005 Aug 1;23(22):5126-37
references: 15983390
references: J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71
references: 16145047
references: J Clin Oncol. 2006 Aug 1;24(22):3629-35
references: 16822845