Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus
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
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.
Bone Reports
https://doi.org/10.1016/j.bonr.2020.100279
Antiretroviral therapy
Sclerostin
10.1016/j.bonr.2020.100279
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Bone Density Medicine & Life Sciences
Tenofovir Medicine & Life Sciences
Catenins Medicine & Life Sciences
Osteocytes Medicine & Life Sciences
Bone and Bones Medicine & Life Sciences
Wnt Signaling Pathway Medicine & Life Sciences
Femur Neck Medicine & Life Sciences
Ross, R. D., Sharma, A., Shi, Q., Hoover, D. R., Weber, K. M., Tien, P. C., French, A. L., Al-Harthi, L., & Yin, M. T. (2020). Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus. Bone Reports, 12, [100279]. https://doi.org/10.1016/j.bonr.2020.100279
Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus. / Ross, Ryan D.; Sharma, Anjali; Shi, Qiuhu; Hoover, Donald R.; Weber, Kathleen M.; Tien, Phyllis C.; French, Audrey L.; Al-Harthi, Lena; Yin, Michael T.
In: Bone Reports, Vol. 12, 100279, 06.2020.
Ross, RD, Sharma, A, Shi, Q, Hoover, DR, Weber, KM, Tien, PC, French, AL, Al-Harthi, L & Yin, MT 2020, 'Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus', Bone Reports, vol. 12, 100279. https://doi.org/10.1016/j.bonr.2020.100279
Ross RD, Sharma A, Shi Q, Hoover DR, Weber KM, Tien PC et al. Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus. Bone Reports. 2020 Jun;12. 100279. https://doi.org/10.1016/j.bonr.2020.100279
Ross, Ryan D. ; Sharma, Anjali ; Shi, Qiuhu ; Hoover, Donald R. ; Weber, Kathleen M. ; Tien, Phyllis C. ; French, Audrey L. ; Al-Harthi, Lena ; Yin, Michael T. / Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus. In: Bone Reports. 2020 ; Vol. 12.
@article{b5d8559b6d504ec3b69075931f484ae0,
title = "Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus",
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.",
keywords = "Antiretroviral therapy, Bone, Bone mineral density, HIV, Sclerostin, Tenofovir",
author = "Ross, {Ryan D.} and Anjali Sharma and Qiuhu Shi and Hoover, {Donald R.} and Weber, {Kathleen M.} and Tien, {Phyllis C.} and French, {Audrey L.} and Lena Al-Harthi and Yin, {Michael T.}",
note = "Funding Information: The authors would like to thank the participants in the WIHS cohort study who participated in the MSK study. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). Data in this manuscript were collected by the Women's Interagency HIV Study, now the MACS/WIHS Combined Cohort Study (MWCCS); additional biomarker testing and data analyses for this manuscript were supported by National Institute Of Allergy And Infectious Diseases (NIAID) funding to the Chicago WIHS ; 5U01AI034992-24 (Mardge Cohen, Audrey French). WIHS/MWCCS (Principal Investigators) for this project/manuscript include: Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146240; Connie Wofsy Women's HIV Study, Northern California CRS (Bradley Aouizerat and Phyllis Tien), U01-HL146242; Data and biomarkers for this manuscript were supported by funding from National Institute Of Allergy And Infectious Diseases (NIAID); the MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute Of Allergy And Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Funding Information: Additional support was provided by the Rush University Scientific Leadership Council via a musculoskeletal pilot grant (RDR), the National Institutes of Health through Grants AI059884 (MTY), AR061993 (AS) and the National Center for Advancing Translation Sciences , through Grant Number UL1TR001873 .",
doi = "10.1016/j.bonr.2020.100279",
journal = "Bone Reports",
T1 - Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus
AU - Ross, Ryan D.
AU - Sharma, Anjali
AU - Shi, Qiuhu
AU - Hoover, Donald R.
AU - Weber, Kathleen M.
AU - Tien, Phyllis C.
AU - French, Audrey L.
AU - Al-Harthi, Lena
AU - Yin, Michael T.
N1 - Funding Information: The authors would like to thank the participants in the WIHS cohort study who participated in the MSK study. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). Data in this manuscript were collected by the Women's Interagency HIV Study, now the MACS/WIHS Combined Cohort Study (MWCCS); additional biomarker testing and data analyses for this manuscript were supported by National Institute Of Allergy And Infectious Diseases (NIAID) funding to the Chicago WIHS ; 5U01AI034992-24 (Mardge Cohen, Audrey French). WIHS/MWCCS (Principal Investigators) for this project/manuscript include: Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146240; Connie Wofsy Women's HIV Study, Northern California CRS (Bradley Aouizerat and Phyllis Tien), U01-HL146242; Data and biomarkers for this manuscript were supported by funding from National Institute Of Allergy And Infectious Diseases (NIAID); the MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute Of Allergy And Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Funding Information: Additional support was provided by the Rush University Scientific Leadership Council via a musculoskeletal pilot grant (RDR), the National Institutes of Health through Grants AI059884 (MTY), AR061993 (AS) and the National Center for Advancing Translation Sciences , through Grant Number UL1TR001873 .
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - Bone mineral density
KW - HIV
KW - Sclerostin
KW - Tenofovir
U2 - 10.1016/j.bonr.2020.100279
DO - 10.1016/j.bonr.2020.100279
JO - Bone Reports
JF - Bone Reports