Giving patients taking tenofovir supplements of vitamin D helped reduces levels of a hormone – parathyroid hormone or PTH - that causes loss of calcium from the bones, a joint London/New York study has found.
Although osteopenia and osteoporosis (loss of calcium from the bones) are common in people with HIV, both on and off therapy, tenofovir, one of the most widely used drugs, has also been associated in some studies with higher levels of bone mineral loss. However, the mechanism for this is unclear, or even whether tenofovir is a direct cause of osteopenia at all.
Vitamin D is essential for bone metabolism and, in both this study and another presented at the BHIVA conference this year, appears to be almost universally deficient in people with HIV.
The researchers, from King’s College Hospital in London and Mount Sinai Hospital in New York, theorised that the ‘missing link’ between HIV, tenofovir, vitamin D and calcium loss is parathyroid hormone (PTH). This hormone causes calcium to be released from the bones into the bloodstream, where it is needed for regulation of the nervous system; in turn, high calcium levels stop the release of PTH, in a feedback loop. However if parathyroid hormone levels become set at too high a level, too much calcium is released from the bones.
The hypothesis investigated by the researchers is that HIV somehow causes low vitamin D levels, which cause the blood to be low in calcium. This pushes up PTH levels, which cause some of the bone mineral loss seen in HIV infection. PTH levels are then are further increased by tenofovir, and thus make the bone mineral loss worse.
The team therefore measured vitamin D and PTH levels in 45 men who were taking HIV drugs. They found sub-optimal vitamin D levels (defined as below 30 nanograms per millilitre) in the majority of the men – 71% – and 41% had higher-than-normal levels of PTH.
All the patients with high PTH were taking tenofovir, and no subject whose levels of vitamin D were normal or above had high PTH.
Seventeen of the 45 patients were advised to take vitamin D supplements because they had very low levels; of these, 14 reported good adherence to the supplement. Vitamin D levels increased in all 14 and PTH levels decreased in nine of the 14. The higher the patients’ original PTH values were, the greater the fall in PTH they experienced on vitamin D. The five patients with the highest baseline levels of PTH had the greatest decreases in PTH; these were in the order of a threefold decline, and went down to normal values. All of these patients were taking tenofovir. In contrast, in the six patients with the lowest baseline PTH, levels stayed exactly the same.
This is a small preliminary study and the results need to be treated with caution. In the first place, the study is too small to eliminate possible confounders – other reasons people might have low vitamin D or high PTH. Secondly, given that vitamin D deficiency appears nearly universal in patients with HIV (another study looking at over 1000 patients at King’s College Hospital found below-normal vitamin D levels in 91% of patients) it is uncertain what the clinical significance of this is or whether vitamin D supplementation, for patients taking tenofovir or otherwise, will help to improve bone mineral loss.
Childs K et al. Vitamin D and calcium supplements reverse the secondary hyperparathyroidism that commonly occurs in HIV patients on TDF-containing HAART. Fifteenth BHIVA Conference, Liverpool, poster P89, 2009.
Welz T et al. Risk factors for vitamin D in an ethnically diverse urban HIV cohort: which antiretrovirals are implicated? Fifteenth BHIVA Conference, Liverpool, oral presentation O6, 2009.