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Vitamin D Plus Calcium Improves Bone Density in HIV Youth Who Start With Low Density
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AIDS 2024, July 22-26, 2024, Munich
Mark Mascolini
High-dose vitamin D3 plus low-dose calcium yielded better bone density than placebo in adolescents with HIV who started a randomized trial of this strategy with low bone mineral density (BMD) [1]. And three quarters of these 11- to 19-year-olds with perinatally acquired HIV in Zambia and Zimbabwe did start the study with low BMD.
Research links HIV infection to stunted growth, delayed puberty, and low bone density, according to VITALITY Trial researchers who conducted this study (https://www.vitality-trial.co.uk). These HIV-related growth problems can be more prevalent in African regions with endemic malnutrition, high rates of non-HIV infections, and delayed antiretroviral therapy (ART) in children with HIV.
How much bones grow during puberty has lifelong consequences, Rashida Ferrand (London School of Hygiene and Tropical Medicine) and colleagues noted. When linear growth and skeletal maturation top out in growing youngsters, their peak bone mass dictates adult BMD. Low BMD at peak bone mass explains 60% of lifetime osteoporosis risk, the researchers said.
VITALITY investigators planned the trial to test this hypothesis: Adjuvant treatment with weekly vitamin D3 and daily calcium carbonate given during adolescence (period of rapid growth) will promote bone accrual and mineralization and maximize peak bone mass and optimize adult bone health.
VITALITY is an individually randomized, placebo-controlled, double-blind trial of 11- to 19-year-olds with perinatally acquired HIV and taking ART for more than 6 months in Zambia or Zimbabwe. Researchers randomized them to once-weekly high-dose vitamin D (20,000 IU) and daily low-dose calcium (500 mg), or to placebo, for 48 weeks. They assessed the primary outcome (total body less head BMD Z score [2]) by intention-to-treat linear regression analysis adjusted for country, baseline value of outcome variable, and any imbalanced factors.
The research team randomized 421 youngsters to the intervention arm and 422 to placebo. After excluding participants who left the study, became pregnant, or did not meet certain data requirements, the primary analysis wound up with 380 adolescents (90.3% of 421) in the treatment arm and 371 (88.1% of 421) in the placebo group. Vitamin D recipients proved similar to placebo takers in proportion of females (53.4% and 53.0%), median age (15 and 15 years), median ART duration (9.7 and 9.9 years), percent with an HIV load below 60 copies (65.8% and 62.2%), median CD4 count (567 and 568), percent taking tenofovir disoproxil fumarate (83.1% and 80.3%), percent taking dolutegravir (80.0% and 80.8%), and height-for-age Z score below 2 (28.7% and 30.2%). When VITALITY began, three quarters of enrollees in the vitamin D and placebo groups had a 25-hydroxyvitamin D [25(OH)D] level below 75 nmol/L (78.6% and 73.2%), indicating vitamin D insufficiency.
Vitamin D and calcium supplementation did not significantly affect overall 48-week BMD Z score, which averaged -1.53 in the treated group and -1.56 in the placebo group (adjusted mean difference 0.03, 95% confidence interval [CI] -0.02 to 0.08, P = 0.11). Nor did the treated and placebo groups differ significantly in lumbar spine bone mineral apparent density after 48 weeks (-0.64 and -0.71, adjusted mean difference 0.04, 95% CI -0.02 to 0.11, P = 0.10). At week 48 the vitamin D group had a higher average 25(OH)D level than the placebo group (80.5 vs 66.7 nmol/L). And the intervention group had a lower proportion with 25(OH)D below 75 nmol/L at 48 weeks (48.2% vs 72.2%).
In adolescents who entered the study with 25(OH)D levels below 75 nmol/L, supplementation did yield a significantly greater total body less head BMD Z score than did placebo (-1.53 vs -1.61, adjusted mean difference 0.04, 95% CI 0.00 to 0.08, P = 0.027). Lumbar spine BMD Z score was also significantly better with supplementation than with placebo (-0.64 vs -0.71, adjusted mean difference 0.04, 95% CI 0.02 to 0.11, P = 0.016).
The researchers recorded no drug-related severe adverse events with high-dose vitamin D and low-dose calcium.
This largest study of vitamin D supplementation in children with HIV found that the vitamin D/calcium regimen did not affect overall BMD change after 48 weeks when compared with placebo. But in the three quarters of trial participants who started the study with low D levels, high-dose vitamin D plus low-dose calcium had a significant positive impact on total body less head BMD Z score and lumbar spine BMD Z score compared with placebo.
VITALITY investigators proposed that—taken during adolescence—this safe, cheap, and readily available intervention may boost bone accrual enough to help youngsters with HIV reach peak bone mass high enough to trim fracture risk later in life.
References
1. Ferrand R, Dzavakwa N, Kasonka L, et al. Randomised placebo-controlled trial of high-dose vitamin D and low-dose calcium supplementation to improve bone density in adolescents with perinatally-acquired HIV in Southern Africa. AIDS 2024, July 22-26, 2024, Munich. Abstract OAB2102.
2. "A Z-score compares your bone density to the average values for a person of your same age and gender. A low Z-score (below -2.0) is a warning sign that you have less bone mass (and/or may be losing bone more rapidly) than expected for someone your age." New York State Department of Health. Bone mineral density testing. https://www.health.ny.gov/publications/2045/
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