title: Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids.
abstract: The role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone.
  
  
  BACKGROUND
  Recent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism.
  
  
  METHODS
  We performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients.
  
  
  RESULTS
  Serum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52 ± 27.21 pmol/L, non-ADT 48.24 ± 15.93 pmol/L, healthy controls 38.48 ± 9.19 pmol/L, p < 0.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: r = -0.309, p = 0.029; bioavailable testosterone: r = -0.280, p = 0.049; free testosterone: r = -0.299, p = 0.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group.
  
  
  CONCLUSIONS
  Circulating sclerostin levels are significantly increased in patients with PC and particularly in those receiving ADT. The inverse relationship between serum sclerostin and testosterone in these patients suggests that androgens are key regulators of bone metabolism in this population.
authors.affiliation: Bone Metabolic Unit, Endocrinology Division (RETICEF), Hospital Universitario San Cecilio, Avda. Doctor Olóriz 16, 18012, Granada, Spain.
authors.forename: B
authors.initials: B
authors.lastname: García-Fontana
authors.forename: S
authors.initials: S
authors.lastname: Morales-Santana
authors.forename: M
authors.initials: M
authors.lastname: Varsavsky
authors.forename: A
authors.initials: A
authors.lastname: García-Martín
authors.forename: J A
authors.initials: JA
authors.lastname: García-Salcedo
authors.forename: R
authors.initials: R
authors.lastname: Reyes-García
authors.forename: M
authors.initials: M
authors.lastname: Muñoz-Torres
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling / Q000502:physiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D013739:Testosterone / Q000097:blood*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D009363:Neoplasm Proteins; C422903:SOST protein, human; D013739:Testosterone; D004958:Estradiol
references.citation: Coll Antropol. 2010 Apr;34 Suppl 2:119-25
references.pmid: 21302710
references.citation: Endocrinology. 2004 Oct;145(10):4685-92
references.pmid: 15217980
references.citation: J Biol Chem. 2005 May 20;280(20):19883-7
references.pmid: 15778503
references.citation: Bone. 2012 Jul;51(1):153-7
references.pmid: 22579776
references.citation: J Clin Endocrinol Metab. 2012 Jan;97(1):234-41
references.pmid: 22031520
references.citation: Biochem Biophys Res Commun. 2012 Jul 20;424(1):170-5
references.pmid: 22735261
references.citation: Cancer. 2005 May 15;103(10):2042-52
references.pmid: 15830347
references.citation: Osteoporos Int. 1993 May;3(3):138-47
references.pmid: 8481590
references.citation: J Biol Chem. 2006 Aug 11;281(32):22429-33
references.pmid: 16793760
references.citation: Cytokine Growth Factor Rev. 2004 Feb;15(1):49-60
references.pmid: 14746813
references.citation: Curr Opin Cell Biol. 2008 Apr;20(2):119-25
references.pmid: 18339531
references.citation: J Bone Miner Res. 2011 Feb;26(2):373-9
references.pmid: 20721932
references.citation: Calcif Tissue Int. 2010 Aug;87(2):99-107
references.pmid: 20473488
references.citation: BMB Rep. 2011 Jul;44(7):473-7
references.pmid: 21777519
references.citation: J Bone Miner Res. 2011 Jan;26(1):27-34
references.pmid: 20499362
references.citation: Prostate. 2011 Oct 1;71(14):1525-37
references.pmid: 21374653
references.citation: PLoS One. 2011;6(10):e25900
references.pmid: 21991382
references.citation: Bone. 2004 Aug;35(2):448-54
references.pmid: 15268896
references.citation: Nature. 2009 Jan 8;457(7226):219-23
references.pmid: 19129847
references.citation: J Steroid Biochem. 1982 Jun;16(6):801-10
references.pmid: 7202083
references.citation: J Bone Miner Res. 2008 May;23(5):705-14
references.pmid: 18086006
references.citation: J Bone Miner Res. 2009 Oct;24(10):1649-50
references.pmid: 19757998
references.citation: J Androl. 2012 Jul-Aug;33(4):594-600
references.pmid: 21903971
references.citation: World J Urol. 1995;13(6):337-43
references.pmid: 9116752
references.citation: Urology. 1999 Oct;54(4):607-11
references.pmid: 10510915
references.citation: N Engl J Med. 2005 Jan 13;352(2):154-64
references.pmid: 15647578
references.citation: Ann N Y Acad Sci. 2011 Nov;1237:19-23
references.pmid: 22082361
references.citation: Gene. 2003 Dec 4;321:1-15
references.pmid: 14636987
references.citation: Eur J Endocrinol. 2013 Mar 15;168(4):615-20
references.pmid: 23389587
references.citation: J Bone Miner Res. 2006 Aug;21(8):1297-306
references.pmid: 16869728
references.citation: Breast Cancer Res. 2011 Oct 27;13(5):R106
references.pmid: 22032690
references.citation: J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72
references.pmid: 10523012