title: Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer.
abstract: OBJECTIVE
  While their negative impact on bone health is well established, the effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG) are unknown. The aim of the study was to investigate the effects of AI on serum levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.
  
  
  METHODS
  We conducted a prospective longitudinal analysis of 70 postmenopausal women with hormone receptor-positive early breast cancer (BC) treated with anastrozole. All measurements were performed at baseline, 12 and 24 months of treatment. We measured the association of the investigated variables with circulating bone turnover markers, as well as with the BMD.
  
  
  RESULTS
  After 24 months of AI therapy, sclerostin and OPG concentrations increased from 29.5 pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD = 20.6) (p < 0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1 levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD = 12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with the BMD of the femoral neck and of the total hip.
  
  
  CONCLUSIONS
  The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.
authors.affiliation: Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, Philipps-University of Marburg, Baldingerstr. 1, 35041, Marburg, Germany, janniskyvernitakis@gmail.com.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kyvernitakis
authors.forename: Tilman D
authors.initials: TD
authors.lastname: Rachner
authors.forename: Anja
authors.initials: A
authors.lastname: Urbschat
authors.forename: Olaf
authors.initials: O
authors.lastname: Hars
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.forename: Peyman
authors.initials: P
authors.lastname: Hadji
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood*; D015519:Bone Density / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood*; D017698:Postmenopause; D011446:Prospective Studies; D013997:Time Factors; D051153:Wnt Proteins / Q000037:antagonists & inhibitors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; C422903:SOST protein, human; D051153:Wnt Proteins