Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents

J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):238-246. doi: 10.1097/QAI.0000000000002007.


Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth.

Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites.

Methods: Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage.

Results: Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants.

Conclusions: In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Biomarkers*
  • Bone Density*
  • Bone and Bones / metabolism*
  • Calcium
  • Cardiovascular Abnormalities / complications*
  • Child
  • Cohort Studies
  • Echocardiography
  • Female
  • Fibroblast Growth Factors
  • HIV Infections / complications*
  • Humans
  • Infectious Disease Transmission, Vertical*
  • Male
  • Minerals / metabolism*
  • Parathyroid Hormone
  • Phosphates
  • United States
  • Vitamin D / analogs & derivatives


  • Biomarkers
  • Minerals
  • Parathyroid Hormone
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • 25-hydroxyvitamin D
  • Calcium