Osteoporosis International

, Volume 25, Issue 2, pp 645–651 | Cite as

Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids

  • B. García-Fontana
  • S. Morales-Santana
  • M. Varsavsky
  • A. García-Martín
  • J. A. García-Salcedo
  • R. Reyes-García
  • M. Muñoz-Torres
Original Article



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.


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.


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.


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.


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.


Bone metabolism Hypogonadism Prostate cancer Sclerostin Sex steroids 



We thank Amanda Rocío Gonzalez (Fundación Pública Andaluza para la Investigación Biosanitaria de Andalucía Oriental Alejandro Otero (FIBAO) from Hospital Clínico San Cecilio, Granada) for her statistical advice. This work was support in part by Consejería de Salud y Bienestar Social (Junta de Andalucía) Grant (PI05142012) and Fondo de Investigación Sanitaria (Instituto Carlos III) Grants (PI12/02141) and RETICEF (RD06/0013/1014-RD12/0043/0014).

Conflicts of interest



  1. 1.
    Wei JT, Gross M, Jaffe CA, Gravlin K, Lahaie M, Faerber GJ, Cooney KA (1999) Androgen in significant loss of bone density. Urology 54:607–611PubMedCrossRefGoogle Scholar
  2. 2.
    Agarwal MM, Khandelwal N, Mandal AK, Rana SV, Gupta V, Chandra Mohan V, Kishore GV (2005) Factors affecting bone mineral density in patients with prostate carcinoma before and after orchidectomy. Cancer 103:2042PubMedCrossRefGoogle Scholar
  3. 3.
    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352:154–164PubMedCrossRefGoogle Scholar
  4. 4.
    Huang H, He X (2008) Wnt/beta-catenin signaling: new (and old) players and new insight. Curr Opin Cell Biol 20:119–125PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Gordon MD, Nusse R (2006) Wnt signalling: multiple pathways, multiple receptors and multiple transcription factors. J Biol Chem 281:22429–22433PubMedCrossRefGoogle Scholar
  6. 6.
    Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signalling. J Biol Chem 280(20):19883–19887PubMedCrossRefGoogle Scholar
  7. 7.
    Suva LJ (2009) Sclerostin and the unloading of bone. J Bone Miner Res 24:1649–1650PubMedCrossRefGoogle Scholar
  8. 8.
    Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ (2011) Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 6(10):e25900PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672PubMedGoogle Scholar
  10. 10.
    Sodergard R, Backstrom T, Shanbhang V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol 17B to human plasma proteins at body temperature. J Steroid Biochem 16:801–810PubMedCrossRefGoogle Scholar
  11. 11.
    McCloskey EV, Spector TD, Eyres KS, Fern ED, O'Rourke N, Vasikaran S, Kanis JA (1993) The assessment of vertebral deformity: a method for use in population studies and clinical trials. Osteoporos Int 3(3):138–147PubMedCrossRefGoogle Scholar
  12. 12.
    Brunetti G, Oranger A, Mori G, Specchia G, Rinaldi E, Curci P, Zallone A, Rizzi R, Grano M, Colucci S (2011) Sclerostin is overexpressed by plasma cells from multiple myeloma patients. Ann N Y Acad Sci 1237:19–23PubMedCrossRefGoogle Scholar
  13. 13.
    Mendoza-Villanueva D, Zeef L, Shore P (2011) Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFβ-dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res 13(5):R106PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Yavropoulou MP, van Lierop AH, Hamdy NA, Rizzoli R, Papapoulos SE (2012) Serum sclerostin levels in Paget’s disease and prostate cancer with bone metastases with a wide range of bone turnover. Bone 51(1):153–157PubMedCrossRefGoogle Scholar
  15. 15.
    Barnes J, Anthony CT, Wall N, Steiner MS (1995) Bone morphogenetic protein-6 expression in normal and malignant prostate. World J Urol 13(6):337–343PubMedCrossRefGoogle Scholar
  16. 16.
    Spanjol J, Djordjević G, Markić D, Klarić M, Fuckar D, Bobinac D (2010) Role of bone morphogenetic proteins in human prostate cancer pathogenesis and development of bone metastases: immunohistochemical study. Coll Antropol 2:119–125Google Scholar
  17. 17.
    Lee GT, Kwon SJ, Lee JH, Jeon SS, Jang KT, Choi HY, Lee HM, Kim WJ, Lee DH, Kim IY (2011) Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6-IL6 loop. Prostate. doi: 10.1002/pros.21369 Google Scholar
  18. 18.
    Ohyama Y, Nifuji A, Maeda Y, Amagasa T, Noda M (2004) Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis. Endocrinology 145(10):4685–4692PubMedCrossRefGoogle Scholar
  19. 19.
    Sutherland MK, Geoghegan JC, Yu C, Winkler DG, Latham JA (2004) Unique regulation of SOST, the sclerosteosis gene, by BMPs and steroid hormones in human osteoblasts. Bone 35(2):448–454PubMedCrossRefGoogle Scholar
  20. 20.
    Zaman G, Jessop HL, Muzylak M, De Souza RL, Pitsillides AA, Price JS, Lanyon LL (2006) Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen. J Bone Miner Res 21:1297–1306PubMedCrossRefGoogle Scholar
  21. 21.
    Kim BJ, Bae SJ, Lee SY, Lee YS, Baek JE, Park SY, Lee SH, Koh JM, Kim GS (2012) TNF-α mediates the stimulation of sclerostin expression in an estrogen-deficient condition. Biochem Biophys Res Commun 424(1):170–175PubMedCrossRefGoogle Scholar
  22. 22.
    Ghosh D, Griswold J, Erman M, Pangborn W (2009) Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature 457(7226):219–223PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 26(1):27–34PubMedCrossRefGoogle Scholar
  24. 24.
    Sanyal A, Hoey KA, Mödder UI, Lamsam JL, McCready LK, Peterson JM, Achenbach SJ, Oursler MJ, Khosla S (2008) Regulation of bone turnover by sex steroids in men. J Bone Miner Res 23(5):705–714PubMedCrossRefGoogle Scholar
  25. 25.
    Lapauw B, Vandewalle S, Taes Y, Goemaere S, Zmierczak H, Collette J, Kaufman JM (2013) Serum sclerostin levels in men with idiopathic osteoporosis. Eur J Endocrinol 168(4):615–620. doi: 10.1530/EJE-12-1074 PubMedCrossRefGoogle Scholar
  26. 26.
    Varsavsky M, Reyes-Garcia R, Avilés-Perez MD, Gonzalez Ramirez AR, Mijan JL, Muñoz-Torres M (2012) Serum osteoprotegerin and sex steroid levels in patients with prostate cancer. J Androl 33(4):594–600PubMedCrossRefGoogle Scholar
  27. 27.
    Nanes MS (2003) Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene 321:1–15PubMedCrossRefGoogle Scholar
  28. 28.
    Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y (2004) IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 15(1):49–60PubMedCrossRefGoogle Scholar
  29. 29.
    Lee JH, Choi YJ, Heo SH, Lee JM, Cho JY (2011) Tumor necrosis factor-α converting enzyme (TACE) increases RANKL expression in osteoblasts and serves as a potential biomarker of periodontitis. BMB Rep 44(7):473–477PubMedCrossRefGoogle Scholar
  30. 30.
    Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87:99–107PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, Melton LJ III, Khosla S (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26(2):373–379PubMedCrossRefGoogle Scholar
  32. 32.
    García-Martín A, Rozas-Moreno P, Reyes-García R, Morales-Santana S, García-Fontana B, García-Salcedo JA, Muñoz-Torres M (2012) Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 97(1):234–241PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2013

Authors and Affiliations

  • B. García-Fontana
    • 1
  • S. Morales-Santana
    • 2
  • M. Varsavsky
    • 1
  • A. García-Martín
    • 1
  • J. A. García-Salcedo
    • 1
  • R. Reyes-García
    • 1
  • M. Muñoz-Torres
    • 1
  1. 1.Bone Metabolic Unit, Endocrinology Division (RETICEF)Hospital Universitario San CecilioGranadaSpain
  2. 2.Proteomic Research ServiceHospital Universitario San CecilioGranadaSpain

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