Vitamin D, calcium supplementation does little to improve bone mass in teens

For adolescents with perinatally acquired HIV, supplementation with vitamin D₃ and calcium appears to have limited benefit in terms of promoting bone accrual and mineralization, as shown in the phase III VITALITY study.

After 48 weeks of intervention, supplementation with vitamin D₃ 20,000 IU weekly plus calcium carbonate 500 mg daily (intervention arm) had no significant effect on bone density or muscle strength and power compared with placebo (control arm).

The mean total body less-head BMD (TBLH-BMD) Z score at week 48 was –1.53 in the intervention arm vs –1.56 in the control arm (p=0.11), while the mean lumbar spine bone mineral apparent density (LS-BMAD) Z score was –0.64 vs –0.71 (p=0.1), respectively. Maximal grip strength was 31.4 kg in the intervention arm vs 31 kg in the control arm (p=0.85), and maximal jump distance was 155.5 vs 157.3 cm (p=0.084), respectively. [Lancet Child Adolesc Health 2026;doi:10.1016/S2352-4642(25)00301-3]

However, in the subgroup of participants with vitamin D insufficiency (<75 nmol/L) at baseline, the LS-BMAD Z score was significantly higher in the intervention arm than in the control arm (adjusted mean difference, 0.09, 95 percent confidence interval [CI], 0.02–0.16; p=0.025).

Safety testing at week 12 and week 24 led to the identification of 45 cases of hypocalcaemia (<8.5 mg/dL) and 11 cases of hypercalcaemia (>10.5 mg/dL), all of which were mild and asymptomatic, with calcium levels returning to normal at follow-up testing. No drug-related severe adverse events were observed.

“The Z-score gains in response to just 48 weeks of supplementation were modest, and in isolation, of limited clinical significance,” according to the investigators, who also pointed out that in clinical practice, supplementation would likely be maintained throughout adolescence (11–19 years), during which half of skeletal mineral is accrued.

Nevertheless, “supplementation should be considered for adolescents with HIV,” given that vitamin D and calcium supplements are cheap, widely available, safe, and well tolerated, they said.

The investigators argued that the period immediately following the growth spurt may be the most favourable time to intervene to optimize bone health. This period, they said, is critical for bone mineralization of newly formed bone matrix. “Therefore, intervening to optimize bone accrual during this period may also reduce the risk of future adult osteoporotic fractures.”

VITALITY included 842 peripubertal individuals (median age 15 years, 53 percent female) with perinatally acquired HIV and had been taking antiretroviral therapy for a median of 9.8 years. There were 421 participants each in the intervention and control arms. The proportion of participants with detectable viral load (>60 copies per mL) was 34 percent in the intervention arm and 38 percent in the control arm.

Around three-quarters of the population (76 percent) had vitamin D insufficiency, with the proportion being slightly higher in the intervention arm than the control arm (79 percent vs 73 percent). Although the proportion of participants with vitamin D insufficiency decreased by 39 percent between baseline and 48 weeks, nearly 50 percent remained vitamin D-insufficient at the end of the intervention.

Reported adherence throughout the intervention period was 90 percent in the two arms. However, the investigators acknowledged that the two approaches used to assess adherence relied on self-report and might thus overestimate adherence. “Sustained adherence over a long period is challenging, particularly in the age group under study. However, measured 25(OH)D concentrations, an objective assessment of adherence, showed clear increases from baseline in the intervention and not the control arm.”