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Erschienen in: Indian Journal of Pediatrics 6/2019

22.01.2019 | Original Article

Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy

verfasst von: Dalia M. E. El-Mikkawy, Mohja A. Elbadawy, Shereen M. Abd El-Ghany, Dalia Samaha

Erschienen in: Indian Journal of Pediatrics | Ausgabe 6/2019

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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.
Literatur
2.
Zurück zum Zitat 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.PubMed 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.PubMed
3.
Zurück zum Zitat Wallny TA, Scholz DT, Oldenburg J, et al. Osteoporosis in haemophilia–an underestimated co-morbidity? Haemophilia. 2007;13:79–84.CrossRefPubMed Wallny TA, Scholz DT, Oldenburg J, et al. Osteoporosis in haemophilia–an underestimated co-morbidity? Haemophilia. 2007;13:79–84.CrossRefPubMed
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat Baron R, Rawadi G. Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635–43.CrossRefPubMed Baron R, Rawadi G. Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635–43.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179–92.CrossRefPubMed Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19:179–92.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
16.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
17.
Zurück zum Zitat El-Bakry S, Saber N, Zidan H, Samaha D. Sclerostin as an innovative insight towards understanding rheumatoid arthritis. Egypt Rheumatol. 2016;38:71–5.CrossRef El-Bakry S, Saber N, Zidan H, Samaha D. Sclerostin as an innovative insight towards understanding rheumatoid arthritis. Egypt Rheumatol. 2016;38:71–5.CrossRef
18.
Zurück zum Zitat Visnjic D, Kalajzic Z, Rowe DW. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.CrossRefPubMed Visnjic D, Kalajzic Z, Rowe DW. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.CrossRefPubMed
19.
Zurück zum Zitat 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. 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.
Zurück zum Zitat Lewiecki EM, Gordon CM, Baim S, et al. International Society for Clinical Densitometry 2007 adult and pediatric official positions. Bone. 2008;43:1115–21.CrossRefPubMed Lewiecki EM, Gordon CM, Baim S, et al. International Society for Clinical Densitometry 2007 adult and pediatric official positions. Bone. 2008;43:1115–21.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat Bachrach LK, Sills IN. Bone densitometry in children and adolescents. Pediatrics. 2011;127:189–94.CrossRefPubMed Bachrach LK, Sills IN. Bone densitometry in children and adolescents. Pediatrics. 2011;127:189–94.CrossRefPubMed
23.
Zurück zum Zitat Hilliard P, Funk S, Zourikian N, et al. Hemophilia joint health score reliability study. Hemophilia. 2006;12:518–25.CrossRef Hilliard P, Funk S, Zourikian N, et al. Hemophilia joint health score reliability study. Hemophilia. 2006;12:518–25.CrossRef
24.
25.
Zurück zum Zitat Giordano P, Brunetti G, Lassandro G, et al. High serum sclerostin levels in children with haemophilia A. Br J Haematol. 2016;172:293–5. Giordano P, Brunetti G, Lassandro G, et al. High serum sclerostin levels in children with haemophilia A. Br J Haematol. 2016;172:293–5.
27.
Zurück zum Zitat 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.CrossRef 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.CrossRef
28.
Zurück zum Zitat Barnes C, Wong P, Egan B, et al. Reduced bone density among children with severe hemophilia. Pediatrics. 2004;114:e177–81.CrossRefPubMed Barnes C, Wong P, Egan B, et al. Reduced bone density among children with severe hemophilia. Pediatrics. 2004;114:e177–81.CrossRefPubMed
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat 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. 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.
Metadaten
Titel
Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy
verfasst von
Dalia M. E. El-Mikkawy
Mohja A. Elbadawy
Shereen M. Abd El-Ghany
Dalia Samaha
Publikationsdatum
22.01.2019
Verlag
Springer India
Erschienen in
Indian Journal of Pediatrics / Ausgabe 6/2019
Print ISSN: 0019-5456
Elektronische ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-019-02855-1

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