Relation of age, gender, and bone mass to circulating sclerostin levels in women and men

Abstract

Sclerostin is a potent inhibitor of Wnt signaling and bone formation. However, there is currently no information on the relation of circulating sclerostin levels to age, gender, or bone mass in humans. Thus we measured serum sclerostin levels in a population-based sample of 362 women [123 premenopausal, 152 postmenopausal not on estrogen treatment (ET), and 87 postmenopausal on ET] and 318 men, aged 21 to 97 years. Sclerostin levels (mean ± SEM) were significantly higher in men than women (33.3 ± 1.0 pmol/L versus 23.7 ± 0.6 pmol/L, p < .001). In pre- and postmenopausal women not on ET combined (n = 275) as well as in men, sclerostin levels were positively associated with age (r = 0.52 and r = 0.64, respectively, p < .001 for both). Over life, serum sclerostin levels increased by 2.4- and 4.6-fold in the women and men, respectively. Moreover, for a given total-body bone mineral content, elderly subjects (age ≥ 60 years) had higher serum sclerostin levels than younger subjects (ages 20 to 39 years). Our data thus demonstrate that (1) men have higher serum sclerostin levels than women, (2) serum sclerostin levels increase markedly with age, and (3) compared with younger subjects, elderly individuals have higher serum sclerostin levels for a given amount of bone mass. Further studies are needed to define the cause of the age-related increase in serum sclerostin levels in humans as well as the potential role of this increase in mediating the known age-related impairment in bone formation. © 2011 American Society for Bone and Mineral Research.

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References 31

1. 1.

   Barons R, Rawadi G. Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635-2643.

   Not in our library10.1210/en.2007-0270

2. 2.

   Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116:1202-1209.

   Not in our library10.1172/jci28551

3. 3.

   van Bezooijen RL, Roelen BAJ, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199:805-814.

   Not in our library10.1084/jem.20031454

4. 4.

   Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770-26775.

   Not in our library10.1074/jbc.m504308200

5. 5.

   Poole KES, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005;19:1842-1844.

   Not in our library10.1096/fj.05-4221fje

6. 6.

   van Bezooijen RL, ten Dijke P, Papapoulos SE, Lowik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005;16:319-327.

   Not in our library10.1016/j.cytogfr.2005.02.005

7. 7.

   Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68:577-589.

   Not in our library10.1086/318811

8. 8.

   Balemans W, Ebeling M, Patel N, et al. Increase bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10:537-543.

   Not in our library10.1093/hmg/10.5.537

9. 9.

   Staehling-Hampton K, Proll S, Paeper BW, et al. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002;110:144-152.

   Not in our library10.1002/ajmg.10401

10. 10.

    Balemans W, Patel N, Ebeling M, et al. Identification of a 52kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002;39:91-97.

    Not in our library10.1136/jmg.39.2.91

11. 11.

    Li X, Ominsky MS, Niu Q-T, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008;23:860-869.

    Not in our library10.1359/jbmr.080216

12. 12.

    Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24:578-588.

    Not in our library10.1359/jbmr.081206

13. 13.

    Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010;95:1991-1997.

    Not in our library10.1210/jc.2009-2283

14. 14.
    Regulation of circulating sclerostin levels by sex steroids in women and in men · 2010

    No notice
15. 15.

    Gaudio A, Pennisi P, Bratengeier C, et al. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab. 2010;95:2248-2253.

    Not in our library10.1210/jc.2010-0067

16. 16.

    Riggs BL, Melton LJ, Robb RA, et al. Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res. 2004;19:1945-1954.

    Not in our library10.1359/jbmr.040916

17. 17.

    Melton LJ. History of the Rochester Epidemiology Project. Mayo Clin Proc. 1996;71:266-274.

    Not in our library10.4065/71.3.266

18. 18.

    Melton LJ, Looker AC, Shepherd JA, et al. Osteoporosis assessment by whole body region vs. site-specific DXA. Osteoporos Int. 2005;16:1558-1564.

    Not in our library10.1007/s00198-005-1871-y

19. 19.

    Camp JJ, Karwoski RA, Stacy MC, et al. A system for the analysis of whole-bone strength from helical CT images. Proceedings of SPIE. 2004;5369:74-88.

    Not in our library

20. 20.

    Cann CE. Quantitative CT for determination of bone mineral density: a review. Radiology. 1988;166:509-522.

    Not in our library10.1148/radiology.166.2.3275985

21. 21.

    Kalender WA, Felsenberg D, Genant HK, Fischer M, Dequeker J, Reeve J. The European spine phantom: a tool for standardization and quality control in spinal bone mineral measurements by DXA and QCT. Eur J Radiol. 1995;20:83-92.

    Not in our library10.1016/0720-048x(95)00631-y

22. 22.

    Khosla S, Riggs BL, Atkinson EJ, et al. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. 2006;21:124-131.

    Not in our library10.1359/jbmr.050916

23. 23.

    Muller R, Hahn M, Vogel M, Delling G, Ruegsegger P. Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections. Bone. 1996;18:215-220.

    Not in our library10.1016/8756-3282(95)00489-0

24. 24.

    Laib A, Hilderbrand T, Hauselmann HJ, Ruegsegger P. Ridge number density: a parameter for in vivo bone structure analysis. Bone. 1997;21:541-546.

    Not in our library10.1016/s8756-3282(97)00205-6

25. 25.

    Laib A, Hauselmann HJ, Ruegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998;6:329-337.

    Not in our library

26. 26.

    Laib A, Ruegsegger P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-microm-resolution microcomputed tomography. Bone. 1999;24:35-39.

    Not in our library10.1016/s8756-3282(98)00159-8

27. 27.

    Parfitt AM, Mathews CHE, Villaneuva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. J Clin Invest. 1983;72:1396-1409.

    Not in our library10.1172/jci111096

28. 28.

    Terpos E, Christoulas D, Katodritou E, et al. High serum sclerostin correlates with advanced stage, increased bone resorption, reduced osteoblast function, and poor survival in newly-diagnosed patients with multiple myeloma. Blood. 2009;114.

    Not in our library

29. 29.

    Khosla S, Amin S, Singh RJ, Atkinson EJ, Melton LJ, Riggs BL. Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density. Osteoporos Int. 2008;19:1465-1471.

    Not in our library10.1007/s00198-008-0591-5

30. 30.

    Khosla S, Melton LJ, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: A key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998;83:2266-2274.

    Not in our library10.1210/jcem.83.7.4924

31. 31.

    Lips P, Courpron P, Meunier PJ. Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcif Tissue Res. 1978;26:13-17.

    Not in our library10.1007/bf02013227

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