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Decreased bone turnover in HIV-infected children on antiretroviral therapy
Stephanie Shiau1,2,3, Michael T Yin4, Renate Strehlau3
1Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, PH 19-114, New York, NY, 10032, USA.
Insights
Virally suppressed HIV-infected children in South Africa show reduced bone mass, irrespective of immune activation or bone turnover markers. This suggests other factors contribute to persistent bone deficits in these children.
Area of Science:
- Pediatric Endocrinology
- Infectious Diseases
- Bone Metabolism
Background:
- HIV infection in children and adolescents is linked to impaired skeletal growth, including reduced bone mass and altered microarchitecture.
- The precise mechanisms by which HIV compromises bone accrual in pediatric populations remain incompletely understood.
- Understanding these mechanisms is crucial for managing long-term skeletal health in HIV-infected youth.
Purpose of the Study:
- To investigate the interrelationships between immune activation, bone turnover, and bone mass in virally suppressed, pre-pubertal HIV-infected children.
- To compare these relationships in children on different antiretroviral therapy (ART) regimens (ritonavir-boosted lopinavir [LPV/r] vs. efavirenz).
- To assess bone health in the context of immune markers and bone turnover in South African children.
Main Methods:
- A cross-sectional analysis of 219 HIV-infected and 180 HIV-uninfected children from the CHANGES Bone Study in Johannesburg, South Africa.
- Whole body bone mineral content (BMC) was measured using dual x-ray absorptiometry (DXA) and expressed as Z-scores.
- Bone turnover markers (CTx, P1NP) and immune activation markers (IL-6, TNF-alpha, soluble CD14, hs-CRP) were analyzed.
Main Results:
- HIV-infected children exhibited lower whole body BMC Z-scores compared to HIV-uninfected controls.
- While soluble CD14 and hs-CRP were higher in HIV-infected children, IL-6 and TNF-alpha levels were similar between groups.
- Markers of bone resorption (CTx) and bone formation (P1NP) were lower in HIV-infected children, with no significant differences in bone turnover markers between ART regimens.
Conclusions:
- Decreased bone accrual in virally suppressed HIV-infected children may persist independently of immune activation.
- Altered bone turnover does not appear to be the primary driver of reduced bone mass in this cohort.
- These findings highlight the complexity of bone health issues in HIV-infected children, suggesting non-immune or non-turnover related factors may play a significant role.
Abstract:
In this study, we evaluated the relationships between immune activation, bone turnover, and bone mass in virally suppressed HIV-infected children and HIV-uninfected children in South Africa. We found that decreased bone mass may occur or persist independent of immune activation and altered bone turnover.
Purpose:
HIV-infected children and adolescents have deficits in skeletal growth which include decreases in bone mass and alterations in bone microarchitecture. However, the mechanism by which HIV infection compromises bone accrual in children and adolescents is unclear. The goal of this study was to evaluate the relationships between immune activation, bone turnover, and bone mass in a group of pre-pubertal HIV-infected children randomized to remain on ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) or switch to efavirenz-based ART in South Africa virally suppressed at the time of this study.
Methods:
This cross-sectional analysis included 219 HIV-infected and 180 HIV-uninfected children enrolled in the CHANGES Bone Study conducted in Johannesburg, South Africa. Whole body (WB) bone mineral content (BMC) was assessed by dual x-ray absorptiometry and WB BMC Z-scores adjusted for sex, age, and height were generated. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx) and procollagen type I N-terminal propeptide (P1NP), were analyzed. Markers of immune activation were also measured, including cytokines IL-6 and TNF-alpha, as well as soluble CD14 and high-sensitivity C-reactive protein (CRP).
Results:
Compared to uninfected controls, HIV-infected children had lower WB BMC Z-scores, similar IL-6 and TNF-alpha, higher soluble CD14 and high-sensitivity CRP, and lower markers of bone resorption (CTX) and bone formation (P1NP). Bone turnover markers were not different in those remaining on LPV/r or switched to efavirenz.
Conclusions:
Our findings suggest that in HIV-infected children with viral suppression, decreased bone accrual may occur or persist independent of immune activation and altered bone turnover.
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