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Tenofovir and bone loss: treatment causes early changes in thyroid hormone levels
Michael Carter, 2011-06-19 13:40:00
Treatment with tenofovir increases levels of a hormone associated with calcium metabolism, Spanish investigators report in the online edition of AIDS Research and Human Retroviruses. This finding is a possible explanation for the reduced bone density seen in patients treated with this drug.
Low levels of vitamin D were also associated with parathyroid hormone concentrations, leading the study’s authors to suggest, “vitamin D supplementation might be considered in these patients, even in the absence of overt…deficiency, when their doctors are willing to start tenofovir-based cART [combination antiretroviral therapy].”
Bone loss is common in patients with HIV. The causes appear to include HIV infection itself and also treatment with antiretroviral drugs.
In particular, tenofovir (Viread, also in the combination pills Truvada and Atripla) therapy has been associated with an increased risk of bone loss.
The exact mechanisms that lead to this side-effect are uncertain, but disturbances in phosphate levels, kidney toxicities, and vitamin D deficiency may have a role.
There are also some data suggesting a relationship with tenofovir therapy and increased parathyroid hormone levels, especially in patients with low levels of vitamin D. This hormone has an important role in calcium metabolism and therefore the formation of bone.
Investigators in Spain wanted to establish a firmer understanding of the impact of tenofovir therapy, changes in parathyroid hormone, and vitamin D levels.
They therefore designed a study involving 57 patients who start a new combination antiretroviral therapy regimen between 2006 and 2008. Thirty-one of these individuals took treatment that included a tenofovir/FTC (Truvada) backbone, whereas the remaining 26 patients took therapy based upon abacavir/3TC (Kivexa). The most commonly used third drug was efavirenz (Sustiva, also in the combination pill Atripla).
The patients were evaluated at regular intervals over 48 weeks to assess the impact of these treatment regimens on parathyroid hormone levels and vitamin D concentrations.
Baseline levels of parathyroid hormone, calcium, and phosphate were comparable between the patients treated with tenofovir and those taking abacavir.
In addition, broadly comparable proportions of patients in both treatment arms had sub-optimal baseline levels of vitamin D (tenofovir, 58% vs. abacavir, 42%).
After starting therapy, median parathyroid levels were significantly higher among patients taking tenofovir than those treated with abacavir at week 4 (p = 0.01), week 24 (p = 0.008) and week 36 (p = 0.02).
Moreover, a higher proportion of patients taking tenofovir compared to abacavir had levels of this hormone that were above the upper limit of normal (53ng/l) at week 24 (68% vs. 24%, p = 0.01) and week 36 (71% vs. 29%, p = 0.03).
In patients taking tenofovir (but not abacavir) parathyroid hormone concentrations were significantly higher in patients with suboptimal vitamin D concentrations (below 30 μg/l) than individuals with vitamin D concentrations above this level at week 24 (63% vs. 54%, p = 0.05) and week 48 (68% vs. 42%, p = 0.03).
Among patients with suboptimal vitamin D, parathyroid hormone concentrations were significantly higher among tenofovir users than abacavir users at week 4 (p = 0.04), week 24 (p = 0.007), and week 36 (p = 0.09).
The first set of statistical analysis showed that baseline lipodystrophy was associated with increased levels of parathyroid hormone (p = 0.04). Higher levels of this hormone were also associated with lower calcium concentrations at week 4 (p = 0.04) and tenofovir therapy at week 24 (p = 0.01).
Subsequent analysis that controlled for potentially confounding factors showed that tenofovir-containing therapy was an independent predictor of parathyroid levels at week 4 (p = 0.02), week 24 (p = 0.02), and week 36 (p = 0.04).
“We demonstrate that the impact on the hormones that regulate calcium homeostasis, and specifically parathyroid hormone levels, of a new ART regimen based on tenofovir/FYC differs from a regimen including abacavir/3TC,” comment the investigators.
They continue: “The early increase in parathyroid observed in our study in patients starting tenofovir might suggest the possibility that the upregulation of this hormone plays a role in the decrease in bone mineral density associated with the initiation of cART containing tenofovir.”
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