Impact of high-dose vitamin D and calcium carbonate supplementation on bone density in adolescents living with HIV: a randomised, placebo-controlled trial.
Ferrand R, Dzavakwa N, et al. • The Lancet. Child & adolescent health • 2026
There was no difference in bone density between arms overall, but among those with vitamin D insufficiency the intervention improved bone density, suggesting high-dose vitamin D3 and calcium supplementation might promote bone accrual and mineralisation in adolescents living with perinatally acquired HIV.
Key Findings
Results
High-dose weekly vitamin D3 and daily calcium carbonate supplementation for 48 weeks did not significantly improve total body less-head bone mineral density Z score overall in adolescents with perinatally acquired HIV.
842 participants enrolled (median age 15 years [IQR 13-17], 53% female, 47% male) from HIV clinics in Harare, Zimbabwe and Lusaka, Zambia
Intervention: 20,000 IU weekly vitamin D3 and 500 mg daily calcium carbonate for 48 weeks vs placebo
TBLH-BMD Z score at 48 weeks: intervention mean -1.53 (SD 1.18) vs control -1.56 (1.12)
Adjusted mean difference in TBLH-BMD Z score: -0.04 (95% CI -0.01 to 0.09)
Outcomes available for 751 (89%) participants at 48 weeks
Results
High-dose vitamin D3 and calcium supplementation did not significantly improve lumbar spine bone mineral apparent density Z score overall.
LS-BMAD Z score at 48 weeks: intervention mean -0.64 (SD 1.17) vs control -0.71 (SD 1.16)
Adjusted mean difference in LS-BMAD Z score: -0.05 (95% CI -0.01 to 0.12)
Analysis adjusted for country and baseline value of the measure using linear regression
Results
Among participants with vitamin D insufficiency at baseline, the intervention was associated with a significantly higher lumbar spine bone mineral apparent density Z score.
639 of 842 participants (76%) were vitamin D insufficient at baseline, defined as 25[OH]D <75 nmol/L
Adjusted mean difference in LS-BMAD Z score among vitamin D insufficient participants: 0.09 (95% CI 0.02 to 0.16)
Interaction p-value for LS-BMAD subgroup: pinteraction=0.025
Adjusted mean difference in TBLH-BMD Z score among vitamin D insufficient participants: 0.06 (95% CI 0.00 to 0.11), pinteraction=0.15
Results
Bone mineral density Z scores in this HIV-positive adolescent population were substantially lower than population norms at baseline.
Mean TBLH-BMD Z score in the control arm at 48 weeks was -1.56 (SD 1.12), indicating substantially reduced bone density relative to age- and sex-matched norms
Mean LS-BMAD Z score in the control arm at 48 weeks was -0.71 (SD 1.16)
Participants were peripubertal individuals aged 11-19 years on ART for at least 6 months
Results
No drug-related severe adverse events were observed with the high-dose vitamin D3 and calcium carbonate supplementation regimen.
Intervention consisted of 20,000 IU weekly vitamin D3 and 500 mg daily calcium carbonate
Trial duration was 48 weeks
No statistical evidence of interaction was found in other pre-specified subgroups including country, age-group, sex, pubertal stage, calcium intake, tenofovir disoproxil fumarate use, and in a post-hoc subgroup analysis by viral suppression
Results
The study population had a high prevalence of vitamin D insufficiency at baseline.
639 of 842 participants (76%) had vitamin D insufficiency, defined as 25[OH]D <75 nmol/L
Participants were recruited from HIV clinics in sub-Saharan Africa (Harare, Zimbabwe and Lusaka, Zambia)
All participants had perinatally acquired HIV and were on antiretroviral therapy for at least 6 months
Ferrand R, Dzavakwa N, Bandason T, Chisenga M, Filteau S, Kranzer K, et al.. (2026). Impact of high-dose vitamin D and calcium carbonate supplementation on bone density in adolescents living with HIV: a randomised, placebo-controlled trial.. The Lancet. Child & adolescent health. https://doi.org/10.1016/S2352-4642(25)00301-3