Bone Sclerostin and Dickkopf-related Protein-1 Are Positively Correlated with Bone Mineral Density, Bone Microarchitecture, and Bone Strength in Postmenopausal Osteoporosis

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2021 May 26

PMID 34034718

Citations 12

Authors

Jia Peng

Zhang Dong

Zhang Hui

Wang Aifei

Deng Lianfu

Xu Youjia

Affiliations

Soon will be listed here.

Abstract

Background: Wnt-catenin signaling antagonists sclerostin and dickkopf-related protein-1 (Dkk-1) inhibit bone formation and are involved in the pathogenesis of postmenopausal osteoporosis (PO). However, the association between sclerostin and Dkk-1 and bone mineral density (BMD) in women with PO remains unclear.

Objective: This study aimed to determine the association between sclerostin and Dkk-1 and BMD, bone microarchitecture, and bone strength in PO.

Methods: Trabecular bone specimens were obtained from the femoral heads of 76 Chinese women with PO who underwent hip arthroplasty for femoral neck fractures. Micro-computed tomography (Micro-CT) was used to assess the BMD and bone microarchitecture of the trabecular bone. Subsequently, a mechanical test was performed. Finally, sclerostin and Dkk-1 in the bone were measured by enzyme-linked immunosorbent (Elisa) assay. Serum ionized serum ionised calcium, propeptide of type 1 collagen, C-terminal β-telopeptide of type-1 collagen, sclerostin, and Dkk-1 were also detected.

Results: Bone sclerostin was positively correlated with serum ionised calcium, serum sclerostin, BMD, bone volume/tissue volume (BV/TV), trabecular number (Tb.N), maximum compressive force, and yield strength (r = 0.32, 0.906, 0.355, 0.401, 0.329, 0.355, and 0.293, respectively, P < 0.05) and negatively correlated with age and trabecular separation (Tb.Sp) (r = - 0.755 and - 0.503, respectively, P < 0.05). Bone Dkk-1 was positively correlated with serum ionised calcium, serum Dkk-1, BMD, BV/TV, trabecular thickness, Tb.N, maximum compressive force, yield strength, and Young's modulus (r = 0.38, 0.809, 0.293, 0.293, 0.228, 0.318, 0.352, 0.315, and 0.266, respectively, P < 0.05) and negatively correlated with age and Tb.Sp (r = - 0.56 and - 0.38, respectively, P < 0.05). Serum levels of sclerostin and Dkk-1 reflected the levels of sclerostin and Dkk-1 in the bone.

Conclusion: Bone sclerostin and Dkk-1 were positively correlated with BMD in women with PO, and higher levels of bone sclerostin and Dkk-1 might predict better BMD, bone microarchitecture, and bone strength. The potential molecular mechanisms still require further study.

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References

Garnero P, Sornay-Rendu E, Munoz F, Borel O, Chapurlat R . Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int. 2012; 24(2):489-94. DOI: 10.1007/s00198-012-1978-x. View

Rossini M, Gatti D, Adami S . Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int. 2013; 93(2):121-32. DOI: 10.1007/s00223-013-9749-z. View

Spatz J, Wein M, Gooi J, Qu Y, Garr J, Liu S . The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro. J Biol Chem. 2015; 290(27):16744-58. PMC: 4505423. DOI: 10.1074/jbc.M114.628313. View

Ahmed S, Fouda N, Abbas A . Serum dickkopf-1 level in postmenopausal females: correlation with bone mineral density and serum biochemical markers. J Osteoporos. 2013; 2013:460210. PMC: 3710636. DOI: 10.1155/2013/460210. View

Dallas S, Prideaux M, Bonewald L . The osteocyte: an endocrine cell ... and more. Endocr Rev. 2013; 34(5):658-90. PMC: 3785641. DOI: 10.1210/er.2012-1026. View

Bellido T . Osteocyte-driven bone remodeling. Calcif Tissue Int. 2013; 94(1):25-34. PMC: 3947228. DOI: 10.1007/s00223-013-9774-y. View

Polyzos S, Anastasilakis A, 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(3):1171-6. DOI: 10.1007/s00198-010-1525-6. View

Polyzos S, Anastasilakis A, Kountouras J, Makras P, Papatheodorou A, Kokkoris P . Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease. J Bone Miner Metab. 2015; 34(4):447-56. DOI: 10.1007/s00774-015-0687-x. View

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. 2010; 26(1):19-26. DOI: 10.1002/jbmr.173. View

10.

Li X, Ominsky M, Warmington K, Morony S, Gong J, Cao J . Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2008; 24(4):578-88. DOI: 10.1359/jbmr.081206. View

11.

Jackle K, Kolb J, Schilling A, Schlickewei C, Amling M, Rueger J . Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women. BMC Musculoskelet Disord. 2020; 21(1):693. PMC: 7574467. DOI: 10.1186/s12891-020-03713-4. View

12.

Gatti D, Viapiana O, Fracassi E, Idolazzi L, Dartizio C, Povino M . Sclerostin and DKK1 in postmenopausal osteoporosis treated with denosumab. J Bone Miner Res. 2012; 27(11):2259-63. DOI: 10.1002/jbmr.1681. View

13.

Szulc P, Boutroy S, Vilayphiou N, Schoppet M, Rauner M, Chapurlat R . Correlates of bone microarchitectural parameters and serum sclerostin levels in men: the STRAMBO study. J Bone Miner Res. 2013; 28(8):1760-70. DOI: 10.1002/jbmr.1888. View

14.

Galea G, Meakin L, Sugiyama T, Zebda N, Sunters A, Taipaleenmaki H . Estrogen receptor α mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute down-regulation of the Wnt antagonist Sost is mediated by estrogen receptor β. J Biol Chem. 2013; 288(13):9035-48. PMC: 3610976. DOI: 10.1074/jbc.M112.405456. View

15.

Brunkow M, Gardner J, Van Ness J, Paeper B, Kovacevich B, Proll S . Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001; 68(3):577-89. PMC: 1274471. DOI: 10.1086/318811. View

16.

Mirza F, Padhi I, Raisz L, Lorenzo J . Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010; 95(4):1991-7. PMC: 2853994. DOI: 10.1210/jc.2009-2283. View

17.

Florio M, Gunasekaran K, Stolina M, Li X, Liu L, Tipton B . A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nat Commun. 2016; 7:11505. PMC: 4894982. DOI: 10.1038/ncomms11505. View

18.

Winkler D, Sutherland M, Geoghegan J, Yu C, Hayes T, Skonier J . Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003; 22(23):6267-76. PMC: 291840. DOI: 10.1093/emboj/cdg599. View

19.

McClung M, Grauer A, Boonen S, Bolognese M, Brown J, Diez-Perez A . Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014; 370(5):412-20. DOI: 10.1056/NEJMoa1305224. View

20.

Manolagas S, Parfitt A . What old means to bone. Trends Endocrinol Metab. 2010; 21(6):369-74. PMC: 2880220. DOI: 10.1016/j.tem.2010.01.010. View