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Decreased bone turnover in HIV-infected children on antiretroviral therapy PowerPoint Presentation

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Description : Decreased bone turnover in HIV-infected children on antiretroviral therapy

Tags : Pediatrics, Child Health, pediatric practice, pediatrician, health providers, HIV-infected infants, Adolescent Transition, HIV-infected adolescents, epidemiology, south Africa, antiretroviral therapy

Published on : Jul 16, 2020 | Views : 1796 | Downloads : 0

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Decreased bone turnover in HIV-infected children on antiretroviral therapy Stephanie Shiau1, Stephen M. Arpadi1, Renate Strehlau2, Faeezah Patel2, Ndileka Mbete2, Donald J. McMahon1, Louise Kuhn1, Ashraf Coovadia2, Michael T. Yin1 1Columbia University, New York, NY, USA 2University of the Witwatersrand, Johannesburg, South Africa O-12 1 CHANGES Bone Study Team
Slide 2-

HIV and Bone in Children HIV appears to be associated with deficits in childhood bone mass accrual1,2 We previously reported lower bone mineral content (BMC) among South African HIV-infected children who3: Initiated treatment early in life Have excellent virologic control Disruption of bone accrual can compromise adult peak bone mass and increase the risk of later life osteoporosis and fracture 1Jacobson et al. AIDS 2010; 2Mora et al. J Clin Endocrinol Metab 2004; 3Arpadi, Shiau, Strehlau et al. AIDS 2016 (in press) 2
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Mechanisms Unclear ? HIV ↓ Bone Mass 3
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Hypothesized Mechanisms HIV Bone ↓ Formation ↓ P1NP ↓ Bone Mass osteoclast ↑ Bone Resorption ↑ CTX ↑Inflammation ↑ IL-6 ↑ TNFα ↑ sCD14 ↑ hs CRP 4 osteoblast
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Previous Studies HIV Bone ↓ Formation ↓ P1NP ↓ Bone Mass ↑Inflammation ↑ IL-6 ↑ TNFα ↑ sCD14 ↑ hs CRP osteoclast ↑ Bone Resorption ↑ CTX osteoblast 1Yin Clin Endocrinol Metab 2010 1 5
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Study Design CHANGES Bone Study ESRU, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa 219 HIV-infected children 219 HIV-uninfected controls 180 controls included in this analysis 6
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Measurements 7 Bone mass Whole body BMC by DXA BMC Z-scores (adjusted for sex, age, and height) Bone turnover markers Resorption: CTX (C-telopeptide) Formation: P1NP (procollagen type 1 N-terminal propeptide) Inflammation IL-6 TNF-α sCD14 hs-CRP
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Results: Characteristics 8
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Results: Inflammation Marker HIV+ (N=219) HIV- (N=180) – – ↑ ↑ 9
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HIV ↓ Bone Mass Results: Bone Resorption osteoclast ↑ Bone Resorption CTX ↑Inflammation 10
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HIV ↓ CTX ↓ Bone Mass ↑ Bone Resorption Results: Bone Resorption osteoclast ↑Inflammation 1 0.5 0 *p<0.05 11 1.5 2.5 2 HIV+ HIV- CTX (ng/mL) *
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Results: Bone Formation HIV ↓ Bone Mass Bone ↓ Formation P1NP Inflammation *p<0.05 12 osteoblast
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Results: Bone Formation HIV ↓ Bone Mass Bone ↓ Formation Inflammation osteoblast 640 620 600 580 560 540 520 500 *p<0.05 13 HIV+ HIV- P1NP (ng/mL) ↓ P1NP *
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Results: Correlations *p<0.05 14
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Summary 15 Compared to HIV-uninfected controls, HIV-infected children had: Lower BMC Similar IL-6 and TNF-a Higher sCD14 and hsCRP Lower bone resorption (CTX) and bone formation (P1NP) Bone turnover markers were not strongly correlated with markers of inflammation or BMC In summary, HIV-infected children with virologic suppression on antiretrovirals had lower BMC and lower bone formation
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Implications 16 In HIV-infected children with viral suppression, decreases in bone accrual may occur independently of immune activation HIV viral proteins and/or ART may have a direct effect on osteoblasts resulting in decreased bone formation1-3 Longitudinal studies that include bone turnover markers are needed to understand the dynamics of bone remodeling in growing children 1Fakruddin Arch Virol 2005; 2Butler J Orthop Res 2013; 3Malizia AIDS Res Hum Retro 2007
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Acknowledgements We thank the CHANGES Study Team and Study Participants Funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 073977, HD 073952) 17

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