Skip to main content
Log in

Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy

  • Original Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objective

To assess serum sclerostin levels in relation to severity of arthropathy and bone mineral density (BMD) in children with hemophilic arthropathy.

Methods

This cross-sectional study included 40 male children suffering from Hemophilia A, and 10 matched healthy controls. Assessment of factor VIII deficiency degree, frequency of bleeding, type of treatment, body mass index (BMI), disease severity using the Hemophilia Joint Health Score (HJHS) and lumbar spine (LS) Z score for bone mineral density (BMD) using dual-energy X-ray absorbiometry was done. Serum sclerostin levels were measured for all patients and controls.

Results

Significant difference of serum sclerostin levels between the patient and control groups with Mean ± SD (0.09 ± 0.07 ng/ml) and (0.04 ± 0.01 ng/ml) (P value = 0.028) respectively was found. Significant positive correlations between serum sclerostin levels and the patients’ age, and HJHS (P value <0.05) were found, while it had negative correlation with DEXA Z score, not reaching a significant value. LS-BMD-Z score levels ranged from (−4.5 to 1.2), with 15 patients with low BMD Z score (less than −2) representing 37.5% of total patients.

Conclusions

Serum sclerostin levels are elevated in hemophilic children denoting bone metabolism affection and correlates with increased age, and HJHS. Increased levels of serum sclerostin may identify hemophilic patients at high risk for developing osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Hoyer LW. Hemophilia A. New Engl J Med. 1994;330:38–47.

    Article  CAS  PubMed  Google Scholar 

  2. Gallacher SJ, Deighan C, Wallace AM, et al. Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study. Q J Med. 1994;87:181–6.

    CAS  PubMed  Google Scholar 

  3. Wallny TA, Scholz DT, Oldenburg J, et al. Osteoporosis in haemophilia–an underestimated co-morbidity? Haemophilia. 2007;13:79–84.

    Article  CAS  PubMed  Google Scholar 

  4. Nair AP, Jijina F, Ghosh K, Madkaikar M, Shrikhande M, Nema M. Osteoporosis in young hemophiliacs from western India. Am J Hematol. 2007;82:453–7.

    Article  PubMed  Google Scholar 

  5. Baron R, Rawadi G. Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635–43.

    Article  CAS  PubMed  Google Scholar 

  6. Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006;116:1202–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199:805–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Semënov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770–5.

    Article  CAS  PubMed  Google Scholar 

  9. Poole KE, van Bezooijen RL, Loveridge N. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. 2005;19:1842–4.

    Article  CAS  PubMed  Google Scholar 

  10. van Bezooijen RL, ten Dijke P, Papapoulos SE, Löwik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005;16:319–27.

    Article  CAS  PubMed  Google Scholar 

  11. Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One. 2011;6:e25900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179–92.

    Article  CAS  PubMed  Google Scholar 

  13. 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;68:577–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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;110:144–52.

    Article  PubMed  Google Scholar 

  15. 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;24:578–88.

    Article  CAS  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. El-Bakry S, Saber N, Zidan H, Samaha D. Sclerostin as an innovative insight towards understanding rheumatoid arthritis. Egypt Rheumatol. 2016;38:71–5.

    Article  Google Scholar 

  18. Visnjic D, Kalajzic Z, Rowe DW. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.

    Article  CAS  PubMed  Google Scholar 

  19. Paschou SA, Anagnostis P, Karras S, et al. Bone mineral density in men and children with haemophilia a and B: A systematic review and meta-analysis. Osteoporos Int. 2014;25:2399–407.

  20. Lewiecki EM, Gordon CM, Baim S, et al. International Society for Clinical Densitometry 2007 adult and pediatric official positions. Bone. 2008;43:1115–21.

    Article  PubMed  Google Scholar 

  21. Bishop N, Braillon P, Burnham J, et al. Dual-energy X-ray absorptiometry assessment in children and adolescents with diseases that may affect the skeleton: the 2007 ISCD pediatric official positions. J Clin Densitom. 2008;11:29–42.

    Article  PubMed  Google Scholar 

  22. Bachrach LK, Sills IN. Bone densitometry in children and adolescents. Pediatrics. 2011;127:189–94.

    Article  PubMed  Google Scholar 

  23. Hilliard P, Funk S, Zourikian N, et al. Hemophilia joint health score reliability study. Hemophilia. 2006;12:518–25.

    Article  CAS  Google Scholar 

  24. Fewtrell MS. Bone densitometry in children assessed by dual x ray absorptiometry: uses and pitfalls. Arch Dis Child. 2003;88:795–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Giordano P, Brunetti G, Lassandro G, et al. High serum sclerostin levels in children with haemophilia A. Br J Haematol. 2016;172:293–5.

  26. Clarke BL, Drake MT. Clinical utility of serum sclerostin measurements. Bonekey Rep. 2013;2:361.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hassab HMA, El-Gendy WM, El-Noueam KI, Abd El Ghany HM, Elwan MMA. Serum cartilage oligomeric matrix protein reflects radiological damage and functional status in hemophilic arthropathy patients. Egypt Rheumatol. 2016;38:241–5.

    Article  Google Scholar 

  28. Barnes C, Wong P, Egan B, et al. Reduced bone density among children with severe hemophilia. Pediatrics. 2004;114:e177–81.

    Article  PubMed  Google Scholar 

  29. Tlacuilo-Parra A, Morales-Zambrano R, Tostado-Rabago N, Esparza-Flores MA, Lopez-Guido B, Orozco-Alcala J. Inactivity is a risk factor for low bone mineral density among haemophilic children. Br J Haematol. 2008;140:562–7.

    Article  PubMed  Google Scholar 

  30. EL Naeem RSA, El Hefnawy HEL, El Aziz OAA, El Mikkawy DMEED, Tantawy AAG, El-Ghany SMA. Assessment of bone mineral density and functional status in children with hemophilic arthropathy. Glob Adv Res J Med Med Sci. 2016;5:035–41.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

DME El-M: Collection of patients from clinic, clinical assessment and HJHS assessment, prepare patients data for statistical analysis; MAE: Helped in clinical data assessment and writing the manuscript; SMA El-G: Collection of blood samples; DS: Laboratory analysis of serum sclerostin levels. DME El- M will act as guarantor for this paper.

Corresponding author

Correspondence to Dalia M. E. El-Mikkawy.

Ethics declarations

Conflict of Interest

None.

Source of Funding

None.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Mikkawy, D.M.E., Elbadawy, M.A., Abd El-Ghany, S.M. et al. Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy. Indian J Pediatr 86, 515–519 (2019). https://doi.org/10.1007/s12098-019-02855-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-019-02855-1

Keywords

Navigation