Circulating Sclerostin is Associated with Bone Mineral Density Independent of HIV-serostatus

Overview

Journal Bone Rep

Date 2020 May 27

PMID 32455152

Citations 6

Authors

Ryan D Ross

Anjali Sharma

Qiuhu Shi

Donald R Hoover

Kathleen M Weber

Phyllis C Tien

Audrey L French

Lena Al-Harthi

Michael T Yin

Affiliations

Soon will be listed here.

Abstract

Background: Low bone mineral density (BMD) is commonly observed in people living with HIV (PLWH), however the cause for this BMD loss remains unclear. Sclerostin, a bone-derived antagonist to the Wnt/β-catenin-pathway, suppresses bone remodeling and is positively associated with BMD. The goal of the current study was to investigate associations between sclerostin and BMD in a cohort of HIV-seropositive and demographically-matched seronegative women.

Methods: This cross-sectional analysis used a subset of early postmenopausal women enrolled in the Women's Interagency HIV Study (WIHS). BMD was assessed at the lumbar spine, total hip, femoral neck, and distal and ultradistal radius via dual energy x-ray absorptiometry (DXA). Circulating sclerostin was assessed via commercial ELISAs. Univariate and multivariate linear regression modeling tested associations between sclerostin and BMD after adjusting for a variety of BMD-modifying variables.

Results: HIV-seropositive women had significantly reduced BMD at all skeletal sites compared to HIV-seronegative women. There was no difference in sclerostin levels according to HIV-serostatus (0.25 vs 0.27 ng/mL in HIV-seronegative and HIV-seropositive, respectively, p = 0.71). Circulating sclerostin was positively associated with BMD at all sites in both univariate and multivariate models adjusting for HIV status, age, BMI, and race, although the coefficients of association were attenuated in HIV-seropositive women. The positive association between sclerostin and BMD among seropositive women remained statistically significant after adjusting for ART or tenofovir disoproxil fumarate (TDF) use.

Conclusions: The current study suggests that circulating sclerostin is a biomarker for bone mass for both HIV seronegative and seropositive women using and not using ART. The lower coefficients of association between sclerostin and BMD by HIV status may suggest HIV-induced alternation in osteocyte function.

Citing Articles

The anti-HIV drug abacavir stimulates β-catenin activity in osteoblast lineage cells.

Olali A, Wallace J, Gonzalez H, Carpenter K, Patel N, Winchester L JBMR Plus. 2024; 8(5):ziae037.

PMID: 38590756 PMC: 11001392. DOI: 10.1093/jbmrpl/ziae037.

Impact of Alcohol on Bone Health in People Living With HIV: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis in a Non-Human Primate Model.

Denys A, Norman A, Perrien D, Suva L, Simon L, McDaniel L JBMR Plus. 2023; 7(1):e10703.

PMID: 36699637 PMC: 9850440. DOI: 10.1002/jbm4.10703.

Bone Quality in Relation to HIV and Antiretroviral Drugs.

Olali A, Carpenter K, Myers M, Sharma A, Yin M, Al-Harthi L Curr HIV/AIDS Rep. 2022; 19(5):312-327.

PMID: 35726043 PMC: 10309294. DOI: 10.1007/s11904-022-00613-1.

Human Immunodeficiency Virus (HIV) and Menopause Are Independently Associated With Lower Bone Mineral Density: Results From the Women's Interagency HIV Study.

Sharma A, Hoover D, Shi Q, Tien P, Weber K, Shah J Clin Infect Dis. 2021; 75(1):65-72.

PMID: 34595517 PMC: 9402636. DOI: 10.1093/cid/ciab874.

Bone and fat hormonal crosstalk with antiretroviral initiation.

Olali A, Shi Q, Hoover D, Bucovsky M, Shane E, Yin M Bone. 2021; 154:116208.

PMID: 34547525 PMC: 8671338. DOI: 10.1016/j.bone.2021.116208.

References

Ke H, Richards W, Li X, Ominsky M . Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012; 33(5):747-83. DOI: 10.1210/er.2011-1060. View

Finkelstein J, Brockwell S, Mehta V, Greendale G, Sowers M, Ettinger B . Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab. 2007; 93(3):861-8. PMC: 2266953. DOI: 10.1210/jc.2007-1876. View

Costa A, Cremers S, Dworakowski E, Lazaretti-Castro M, Bilezikian J . Comparison of two commercially available ELISAs for circulating sclerostin. Osteoporos Int. 2014; 25(5):1547-54. DOI: 10.1007/s00198-014-2635-3. View

Morse L, Sudhakar S, Danilack V, Tun C, Lazzari A, Gagnon D . Association between sclerostin and bone density in chronic spinal cord injury. J Bone Miner Res. 2011; 27(2):352-9. PMC: 3288145. DOI: 10.1002/jbmr.546. View

Piec I, Washbourne C, Tang J, Fisher E, Greeves J, Jackson S . How Accurate is Your Sclerostin Measurement? Comparison Between Three Commercially Available Sclerostin ELISA Kits. Calcif Tissue Int. 2016; 98(6):546-55. PMC: 4860200. DOI: 10.1007/s00223-015-0105-3. View

Ellies D, Viviano B, McCarthy J, Rey J, Itasaki N, Saunders S . Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006; 21(11):1738-49. DOI: 10.1359/jbmr.060810. View

Brown T, McComsey G . Osteopenia and osteoporosis in patients with HIV: a review of current concepts. Curr Infect Dis Rep. 2006; 8(2):162-70. DOI: 10.1007/s11908-006-0012-x. View

Voskaridou E, Christoulas D, Plata E, Bratengeier C, Anastasilakis A, Komninaka V . High circulating sclerostin is present in patients with thalassemia-associated osteoporosis and correlates with bone mineral density. Horm Metab Res. 2012; 44(12):909-13. DOI: 10.1055/s-0032-1312618. View

Adimora A, Ramirez C, Benning L, Greenblatt R, Kempf M, Tien P . Cohort Profile: The Women's Interagency HIV Study (WIHS). Int J Epidemiol. 2018; 47(2):393-394i. PMC: 5913596. DOI: 10.1093/ije/dyy021. View

10.

He J, Zhang H, Wang C, Zhang Z, Yue H, Hu W . Associations of serum sclerostin and polymorphisms in the SOST gene with bone mineral density and markers of bone metabolism in postmenopausal Chinese women. J Clin Endocrinol Metab. 2014; 99(4):E665-73. DOI: 10.1210/jc.2013-2086. View

11.

Gibellini D, De Crignis E, Ponti C, Cimatti L, Borderi M, Tschon M . HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation. J Med Virol. 2008; 80(9):1507-14. DOI: 10.1002/jmv.21266. View

12.

Malluche H, Davenport D, Cantor T, Monier-Faugere M . Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol. 2014; 9(7):1254-62. PMC: 4078960. DOI: 10.2215/CJN.09470913. View

13.

Negredo E, Diez-Perez A, Bonjoch A, Domingo P, Perez-Alvarez N, Gutierrez M . Switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels. J Antimicrob Chemother. 2015; 70(7):2104-7. DOI: 10.1093/jac/dkv063. View

14.

Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C . Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002; 39(2):91-7. PMC: 1735035. DOI: 10.1136/jmg.39.2.91. View

15.

Amrein K, Amrein S, Drexler C, Dimai H, Dobnig H, Pfeifer K . Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab. 2011; 97(1):148-54. DOI: 10.1210/jc.2011-2152. View

16.

Erlandson K, ORiordan M, Hileman C, Rapaport E, Labbato D, Campbell T . Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2015; 31(7):731-8. PMC: 4505764. DOI: 10.1089/AID.2015.0052. View

17.

Almansouri A, Abdulfatah M, Baaqil O, Bakheet A, Turki S, Kotb M . Serum Sclerostin Levels in Patients with Human Immunodeficiency Virus Infection and Their Association with Bone Turnover Markers and Bone Mineral Densitometry. J Bone Metab. 2016; 23(1):16-22. PMC: 4791433. DOI: 10.11005/jbm.2016.23.1.16. View

18.

Mahy M, Autenrieth C, Stanecki K, Wynd S . Increasing trends in HIV prevalence among people aged 50 years and older: evidence from estimates and survey data. AIDS. 2014; 28 Suppl 4:S453-9. PMC: 4247270. DOI: 10.1097/QAD.0000000000000479. View

19.

Costagliola D . Demographics of HIV and aging. Curr Opin HIV AIDS. 2014; 9(4):294-301. DOI: 10.1097/COH.0000000000000076. View

20.

Mora S, Puzzovio M, Giacomet V, Fabiano V, Maruca K, Capelli S . Sclerostin and DKK-1: two important regulators of bone metabolism in HIV-infected youths. Endocrine. 2015; 49(3):783-90. DOI: 10.1007/s12020-015-0527-8. View