Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer
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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.
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.
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.
The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.
KeywordsAromatase inhibition Sclerostin DKK-1 OPG Breast cancer
IK and PH conceived the study, participated in its design and coordination, helped to draft the manuscript and made substantial contributions to analysis and interpretation of the data. TR and LH participated in the design of the study, made substantial contributions to acquisition of data and helped to draft the manuscript. AU made substantial contributions to acquisition of data and helped to draft the manuscript. OH participated in the design of the study and performed statistical analyses. All authors read and approved the final manuscript. This work was supported by AstraZeneca (to PH), and the Grants RA 2151/2-1 (to TDR and LCH) and Forschergruppe-1586 SKELMET to LCH from the Deutsche Forschungsgemeinschaft.
Conflict of interest
The authors have received grants or honorarium for advisory boards or lectures to the individual or the institution by Amgen (TDR, LCH, PH), AstraZeneca (PH), Eli Lilly (PH), GlaxoSmithKline (PH), Novartis (TDR, LCH, PH), Pfizer (PH), Roche (PH), Servier (LCH), Merck (LCH, TDR) and Nycomed (LCH). IK, VZ, MS and OH have no conflicts of interest to report.
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