Associations of low vitamin D and elevated parathyroid hormone concentrations with bone mineral density in perinatally HIV-infected children

Authors: JACOBSON, DENISE - Harvard School Of Public Health; Stephensen, Charles; MILLER, TRACIE - University Of Miami; PATEL, KUNJAL - Harvard School Of Public Health; CHEN, JANET - Drexel University; VAN DYKE, RUSSELL - Tulane School Of Medicine; MIRZA, AYESHA - University Of Florida; SCHUSTER, GERTRUD - University Of California; HAZRA, ROHAN - National Institutes Of Health (NIH); ELLIS, ANGELA - Frontier Science & Technology Research Foundation, Inc; BRUMMEL, SEAN - Harvard School Of Public Health; GEFFNER, MITCHELL - University Of Southern California; SILIO, MARGARITA - Tulane School Of Medicine; SPECTOR, STEPHEN - University Of California; DIMEGLIO, LINDA - Indiana University

Submitted to: Journal of Acquired Immune Deficiency Syndromes
Publication Type: Trade Journal
Publication Acceptance Date: 5/30/2017
Publication Date: 5/30/2017
Citation: Jacobson, D.L., Stephensen, C.B., Miller, T.L., Patel, K., Chen, J.S., Van Dyke, R.B., Mirza, A., Schuster, G., Hazra, R., Ellis, A., Brummel, S.S., Geffner, M., Silio, M., Spector, S.A., Dimeglio, L. 2017. Associations of low vitamin D and elevated parathyroid hormone concentrations with bone mineral density in perinatally HIV-infected children. Journal of Acquired Immune Deficiency Syndromes. doi: 10.1097/QAI.0000000000001467.

Interpretive Summary: Children infected with the HIV virus at birth are treated with antiretroviral therapy and can lead relatively healthy lives, but may have lower total-body bone mineral density (TB-BMD) than uninfected children. Vitamin D insufficiency (VDI), as indicated by plasma vitamin D <20 ng/mL, can lead to low BMD because vitamin D is required for calcium absorption from the intestine. This study was conducted to determine if VDI in HIV-positive children had a similar association with BMD as is seen in uninfected children. To this end, HIV-positive and uninfected control children (exposed to HIV at birth) from the Pediatric HIV/AIDS Cohort Study were retrospectively examined for vitamin D status and parathyroid hormone (PTH) concentration at time points close to study visits when BMD was measured by dual-energy x-ray absorptiometry. HIV-positive children (N=412) were older (13.0 vs.10.8 yr) and more often black (76% vs. 64%) than control children (N=207). Children with VDI in both groups had lower TB-BMD than children with adequate vitamin D status but HIV-positive children had higher PTH concentrations, adjusted for vitamin D status, than did control children. This may indicate that calcium absorption is impaired in the HIV-positive group, since PTH increases in response to low blood calcium and both groups had similar calcium levels in their diets. In summary, VDI in both groups of children was similarly associated with low TB-BMD. These data support the need for further work to test interventions to optimize BMD accrual during childhood, a critical period for bone development.

Technical 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 (aPR 1.00; 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.