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Type 2 diabetes raises serum sclerostin levels and disturbs the relation between sclerostin and bone mineral density: a call for caution with antisclerostin therapy in osteoporosis

Egyptian Rheumatology and Rehabilitation volume 41, pages 37–43 (2014)Cite this article

Abstract

Background

Sclerostin is an osteocyte-secreted protein that negatively regulates osteoblasts. Wnt signaling may be crucial in the pathogenesis of impaired bone quality in type 2 diabetes mellitus (T2DM). The possibility that currently studied antisclerostin bone-forming agents could be useful to T2DM patients with osteoporosis needs further investigations.

Aim

The aim of this study was to investigate the relationship between serum sclerostin and bone mineral density in T2DM patients, in comparison with nondiabetic individuals.

Patients and Methods

This study was conducted on 21 T2DM patients and 22 nondiabetic individuals. All participants were 60 years or older. They underwent history taking, clinical examination, routine lab investigations, and glycated hemoglobin assessment. Serum sclerostin was measured by ELISA. Bone mineral density (BMD) was measured at the left femoral neck and lumbar spine.

Results

Serum sclerostin level was significantly higher in T2DM patients compared with nondiabetic individuals. Male participants showed significantly higher sclerostin levels among the nondiabetic individuals, whereas this difference was not significant among T2DM patients. The Bone mineral density (BMD) and f-values of T2DM patients and the nondiabetic group were not significantly different. We found a significant positive correlation between sclerostin level and lumbar spine BMD among nondiabetic individuals, whereas among T2DM patients, this correlation was not significant. Sclerostin levels did not show a significant difference between diabetic osteoporotic and diabetic nonosteoporotic patients.

Conclusion

Patients with T2DM have raised sclerostin levels that, unlike those in nondiabetic individuals. are not correlated with BMD. This pathological condition that is specific to diabetes necessitates further study, careful assessment of the role of antisclerostin therapy, and probable dose adjustment for osteoporosis in T2DM patients.

References

  1. Kneissel M. The promise of sclerostin inhibition for the treatment of osteoporosis. IBMS BoneKEy 2009; 6:259–264.

    Article  Google Scholar 

  2. Rey JP, Ellies DL. Wnt modulators in the biotech pipeline. Dev Dyn 2010; 239:102–114.

    Article  CAS  Google Scholar 

  3. Paszty C, Turner CH, Robinson MK. Sclerostin: a gem from the genome leads to bone-building antibodies. J Bone Miner Res 2010; 25:1897–1904.

    Article  CAS  Google Scholar 

  4. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Baron R, Hesse E. Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab 2012; 97:311–325.

    Article  CAS  Google Scholar 

  7. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011; 26:19–26.

    Article  CAS  Google Scholar 

  8. Thrailkill KM, Lumpkin CK Jr, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 2005; 289:E735–E745.

    Article  CAS  Google Scholar 

  9. Isidro ML, Ruano B. Bone disease in diabetes. Curr Diabetes Rev 2010; 6:144–155.

    Article  Google Scholar 

  10. Abdulameer SA, Sulaiman SA, Hassali MA, Subramaniam K, Sahib MN. Osteoporosis and type 2 diabetes mellitus: what do we know, and what we can do? Patient Prefer Adherence 2012; 6:435–448.

    Article  Google Scholar 

  11. McCabe L, Zhang J, Raehtz S. Understanding the skeletal pathology of type 1 and 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr 2011; 21:187–206.

    Article  CAS  Google Scholar 

  12. Eckel RH, Kahn SE, Ferrannini E, Goldtine AB, Nathan DM, Schwartz MW, et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Endocrine Society; American Diabetes Association; European Association for the Study of Diabetes. Diabetes Care 2011; 34:1424–1430.

    Article  Google Scholar 

  13. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of ADL, a standardized measure of biological and psychosocial function. JAMA 1963; 185:914–919.

    PubMed  CAS  Google Scholar 

  14. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9:179–186.

    Article  CAS  Google Scholar 

  15. Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991; 39:142–148.

    Article  CAS  Google Scholar 

  16. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994; 9:1117–1141.

    Google Scholar 

  17. Lewiecki EM, Watts NB, McClung MR, Petak SM, Bachrach TK, Shepherd JA, et al. Official position of the International Society for Clinical Densitometry. J Clin Endocrinol Metab 2004; 89:3651–3655.

    Article  CAS  Google Scholar 

  18. Martin A, Moreno P, Garcia R, Santana S, Fontana B, Salcedo J, Torres M. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2012; 97:234–241,

    Article  CAS  Google Scholar 

  19. Suva LJ. Sclerostin and the unloading of bone. J Bone Miner Res 2009; 24:1649–1650.

    Article  CAS  Google Scholar 

  20. Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 2010; 25:948–959.

    Article  CAS  Google Scholar 

  21. Papapoulos S. Targeting sclerostin as potential treatment of osteoporosis. Ann Rheum Dis 2011; 70:119–122.

    Article  CAS  Google Scholar 

  22. Gennari L, Merlotti D, Valenti R, Ceccarelli E, Ruvio M, Pietrini M, et al. Decreased bone turn over activity in both type 1 and 2 diabetes mellitus. J Clin Endocrinol Metab 2012; 97:1737–1744.

    Article  CAS  Google Scholar 

  23. Modder Ul, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, et al. Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 2011; 26:27–34.

    Article  CAS  Google Scholar 

  24. 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.

    Article  Google Scholar 

  25. Van Lierop AH, Witteveen JE, Hamdy NA, Papapoulos SE. Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls. Eur J Endocrinol 2010; 163:833–837.

    Article  CAS  Google Scholar 

  26. Ardawi M, Al-Sibiany A, Bakhsh T, AA Rouzi, Qari M. Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study. Osteoporos Int 2012; 23:1789–1797.

    Article  CAS  Google Scholar 

  27. Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, 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.

    Article  CAS  Google Scholar 

  28. Sta Romana M, Li-Yu J. Investigation of the relationship between type 2 diabetes and osteoporosis using Bayesian inference. J Clin Densitom 2007; 10:386–390.

    Article  CAS  Google Scholar 

  29. Kumeda Y. Osteoporosis in diabetes. Clin Calcium 2008; 18:589–599.

    PubMed  CAS  Google Scholar 

  30. Okazaki R. Diabetes mellitus and bone metabolism. Clin Calcium 2011; 21:669–675.

    PubMed  Google Scholar 

  31. Blakytny R, Spraul M, Jude EB. Review: The diabetic bone: a cellular and a molecular perspective. Int J Low Extrem Wounds 2011; 10:16–32.

    Article  Google Scholar 

  32. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes — a meta-analysis. Osteoporos Int 2007; 18:427444.

    Google Scholar 

  33. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 2009; 24:702.

    Article  CAS  Google Scholar 

  34. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 2011; 26:373–379.

    Article  CAS  Google Scholar 

  35. Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E. Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women-the six-month effect of risedronate and teriparatide. Osteoporos Int 2011; 23:1171–1176.

    Article  CAS  Google Scholar 

  36. Sheng Z, Tong D, Ous Y, Zhang H, Zhang Z, Li S, et al. Serum sclerostin levels were positively correlated with fat mass and bone mineral density in Central South Chinese postmenopausal women. Clin Endocrinol 2012; 76:797–801.

    Article  CAS  Google Scholar 

  37. Cejka D, Jaäger-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, et al. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant 2011;27:226–230.

    Article  CAS  Google Scholar 

  38. Ardawi M, Rouzi A, Al-Sibiani S, Al-Senani N, Qari M, Mousa S. High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women. J Bone Miner Res 2012; 27:2592–2602.

    Article  CAS  Google Scholar 

  39. Terpos E, Fragiadaki K, Konsta M, Bratengeier C, Papatheodorou A, Sfikakis PP. Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clin Exp Rheumatol 2011; 29:921–925.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Physical Medicine, Rheumatology, and Rehabilitation, Faculty of medicine, Ain Shams University, 11566, Cairo, Egypt

    Dina S. Al-Zifzaf MD & Eman A. Kaddah

  2. Departments of Geriatrics and Gerontology, Ain Shams University, Cairo, Egypt

    Sarah A. Hamza

  3. Departments of Clinical Pathology, Ain Shams University, Cairo, Egypt

    Rania A. Abo-Shady

Authors
  1. Dina S. Al-Zifzaf MD
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  2. Sarah A. Hamza
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  3. Eman A. Kaddah
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  4. Rania A. Abo-Shady
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Corresponding author

Correspondence to Dina S. Al-Zifzaf MD.

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Al-Zifzaf, D.S., Hamza, S.A., Kaddah, E.A. et al. Type 2 diabetes raises serum sclerostin levels and disturbs the relation between sclerostin and bone mineral density: a call for caution with antisclerostin therapy in osteoporosis. Egypt Rheumatol Rehabil 41, 37–43 (2014). https://doi.org/10.4103/1110-161X.128136

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