Vitamin D supplements benefit bone metabolism of younger patients taking tenofovir

Vitamin D supplementation is associated with an improvement in a key marker of bone health in HIV-positive young adults treated with tenofovir, US research published in Clinical Infectious Diseases shows.

Treatment with vitamin D3 led to a significant fall in parathyroid hormone levels, an important regulator of calcium which has a significant role in bone metabolism. The use of the supplement had a beneficial effect even when patients had sufficient vitamin D levels at baseline.

However, taking vitamin D had no significant impact on parathyroid hormone levels in patients who were not taking tenofovir.

The study only lasted twelve weeks, so the investigators were unable to show if their findings had any impact on bone health.

“Further study with longer follow-up and direct measurements of bone mineral density is needed to define the effect of vitamin D treatment on bone heath in youth using tenofovir.”

HIV treatment guidelines around the world recommend tenofovir (Viread, also in the combination pills Truvada, Eviplera and Atripla) in first-line antiretroviral therapy. The drug is potent, easy to take and has a generally mild side-effect profile.

However, treatment with tenofovir has been associated with a deterioration in kidney function and alterations in bone mineralisation, calcium balance and bone mineral density.

The impact of tenofovir on bone metabolism could be because of its impact on parathyroid hormone levels.

Large numbers of HIV-positive patients have insufficient levels of vitamin D. In HIV-negative individuals this has been associated with poorer kidney function and higher levels of parathyroid hormone. Vitamin D supplements have been shown to have a beneficial effect on both markers. However, the benefit of vitamin D supplements for patients with HIV is controversial.

Investigators from the US Adolescent Medicine Trials Network (ATN) 063 study hypothesised that vitamin D supplementation would have a beneficial effect on parathyroid hormone levels and other markers of bone metabolism in HIV-positive young adults taking tenofovir-based regimens.

They designed a randomised, double-blind placebo controlled trial involving 203 HIV-positive 18 to 25 year olds. All were taking stable antiretroviral therapy and had a viral load below 500 copies/ml. A total of 118 were taking a combination that included tenofovir.

Patients in the intervention arm received 50 000 iu/ml of vitamin D3 at baseline, and again at week four and week eight. Individuals in the control arm were provided with a matching placebo. The effect of the therapy on vitamin D sufficiency, parathyroid hormone levels and other markers of bone metabolism were evaluated at week twelve.

Similar proportions of patients (approximately 52%) in both the treatment and control arms had insufficient levels of vitamin D at baseline.

Among all participants, parathyroid hormone levels were higher among those with insufficient vitamin D (p = 0.024). Moreover, higher levels of parathyroid hormone were significantly associated with tenofovir therapy (p < 0.001).

Supplementation had beneficial effects on vitamin D sufficiency.

At week twelve, 95% of patients in the treatment arm had vitamin D concentrations above the sufficient level of 20 ng/ml. In contrast, the proportion of patients in the placebo arm with vitamin D sufficiency was unchanged from baseline.

Vitamin D therapy for patients taking tenofovir was associated with decreased parathyroid hormone levels and bone turnover.

“These changes…were not seen with vitamin D in the no-tenofovir group, or with placebo in either the tenofovir or no-tenofovir groups,” observe the investigators.

Multivariate analysis confirmed that vitamin D therapy was associated with a significant decrease in levels of parathyroid hormone for those taking tenofovir, but not for individuals taking alternative antiretroviral drugs (p = 0.023).

Vitamin D supplementation had no beneficial effects on parathyroid hormone levels for patients taking non-tenofovir regimens, even when they had vitamin D insufficiency at baseline.

In contrast, the impact of the supplement on parathyroid hormone levels for patients taking tenofovir was independent of baseline levels of vitamin D. Significant reductions in parathyroid hormone levels were seen after supplementation in patients with vitamin D insufficiency at baseline (p = 0.031), and also in patients with sufficient levels of the vitamin (p = 0.053).

Despite these benefits, parathyroid hormone levels were still higher at the end of the study among patients treated with tenofovir compared to those who were not taking this drug (44.5 pg/ml vs. 31.1 ph/ml, p < 0.001).

Vitamin D supplementation appeared safe.

“Our results confirmed our hypothesis that vitamin D treatment would reduce parathyroid hormone in youth on tenofovir-containing regimens,” comment the authors.

They speculate that treatment with the vitamin may correct a “functional vitamin D deficiency” associated with use of tenofovir, even in patients with apparently normal levels of the vitamin.

“These results suggest that vitamin D supplementation may offset a potential effect of tenofovir on regulation of calcium balance and bone metabolism,” conclude the authors.

Havens PL et al. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial. Clin Infect Dis, online edition. DOI: 10.1093/cid/cir968, 2012 (click here for the free abstract).