Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children

Abstract

Background Perinatally HIV-infected (PHIV) children have, on average, lower bone mineral density (BMD) than perinatally HIV-exposed uninfected (PHEU) and healthy children. Low 25-hydroxy vitamin D [25(OH)D] and elevated parathyroid hormone (PTH) concentrations may lead to suboptimal bone accrual. Methods PHIV and PHEU children in the Pediatric HIV/AIDS Cohort Study had total body (TB) and lumbar spine (LS) BMD and bone mineral content (BMC) measured by dual-energy x-ray absorptiometry; BMD z-scores (BMDz) were calculated for age-sex. Low 25(OH)D was defined as ≤20 ng/mL and high PTH as >65 pg/mL. We fit linear regression models to estimate average adjusted differences in BMD/BMC by 25(OH)D and PTH status, and log-binomial models to determine adjusted prevalence ratios (aPR) of low 25(OH)D and high PTH in PHIV relative to PHEU children. Results PHIV children (N=412) were older (13.0 vs.10.8 yr) and more often black (76% vs. 64%) than PHEU (N=207). Among PHIV, children with low 25(OH)D had lower TB-BMDz (−0.38 SD; 95%CI: −0.60 to −0.16) and TB-BMC (−59.1 g; 95%CI: −108.3 to −9.8); high PTH accompanied by low 25(OH)D was associated with lower TB-BMDz. Among PHEU, children with low 25(OH)D had lower TB-BMDz (−0.34 SD; 95%CI: −0.64 to −0.03). Prevalence of low 25(OH)D was similar by HIV status (aPR1.00; 95%CI: 0.81 to 1.24). High PTH was 3.17 (95%CI: 1.25 to 8.06) times more likely in PHIV children. Conclusion PHIV and PHEU children with low 25(OH)D may have lower BMD. Vitamin D supplementation trials during critical periods of bone accrual are needed.

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

“…Although the incidence of VDI and high PTH was higher in black youth 4 , their associations with cardiac outcomes were not statistically significant after adjusting for confounders. However, some associations between other components (calcium, phosphate, and FGF-23) and cardiac outcomes remained significant.…”

“…BMM markers, including 25OHD, PTH, calcium, phosphate, and FGF-23, were measured in PHIV and PHEU children in AMP who had an adequate echocardiogram performed within one year of the sample for BMM markers. Full details of the BMM marker assays used have been reported by Jacobson et al 4 . FGF-23 was measured by ELISA (Kainos Laboratories) and levels were log10-transformed to more closely approximate a normal distribution.…”

“…Disordered bone metabolism and low bone mineral density are common in both adults and children with HIV disease [1][2][3] . We have demonstrated lower total body and lumbar spine bone mineral density in children with perinatal HIV infection (PHIV) than in those who were perinatally HIV-exposed but uninfected (PHEU) 3 , along with a high prevalence (40%) of vitamin D insufficiency (VDI) in both PHIV and PHEU children 4 . Increasing evidence suggests that VDI is associated with several common cardiovascular abnormalities.…”

“…Even though abnormal serum concentrations of bone mineral metabolism (BMM) markers (i.e., 25OHD, PTH, calcium, phosphate, and FGF-23) are common in HIV-infected populations, particularly among those receiving combination antiretroviral therapy 4,11,12 , and are associated with adverse cardiovascular conditions including congestive heart failure 13,14 , it is unknown whether these markers are associated with echocardiographic findings or with NT-proBNP, a biomarker of cardiac function. The objectives of this study were to evaluate associations of BMM marker concentrations with cardiac structure and function (as measured by echocardiography and NT-proBNP) in a population of PHIV and PHEU children, and to descriptively evaluate whether these associations vary by HIV infection status.…”

The impact of vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: A systematic review

“…During childhood and adolescent growth, bones grow in length, width and mineral content until peak bone mass (PBM) is achieved [ 11 ]; PBM is a key determinant of future adult osteoporosis and lifetime fracture risk [ 12 – 14 ]. ‘Low bone mass’, defined as a dual energy X-ray absorptiometry (DXA) measured BMD Z-score ≤ -2 has been associated with low 25OHD and altered vitamin D metabolism in HIV-positive youths [ 15 , 16 ]. Furthermore, HIV infection increases bone turnover to reduce BMD even when vitamin D concentration is adequate [ 16 ].…”