Important note: Information in this article was accurate in August 2000. The state of the art may have changed since the publication date.
A growing number of reports have been made about PHAs who have developed thin and weakened bones, a condition that places them at an increased risk for fractures. In other cases, some people have developed severe joint damage that required hip replacement surgery. It is not yet certain if these complications are due to the impact of HAART, long-term HIV infection or some weird interaction between the two. If osteoporosis (decreased bone mass) proves to be caused by HAART, researchers will have to find out which components of anti-HIV drug regimens - nukes, non-nukes or protease inhibitors - are contributing to the thinning of bones in people with HIV.
Calcium is a mineral that is used together with phosphorus and magnesium to build healthy bones. It is possible that some PHAs are developing osteoporosis because their bodies are unable to retain the calcium absorbed from their diet. In one experiment, researchers studied 73 HIV-positive subjects receiving combination anti-HIV therapy that included a protease inhibitor. After analysing urine samples, researchers found that 50% of subjects were losing more than 200 mg of calcium each day. X-ray results led the researchers to conclude that the subjects' bones were losing minerals and becoming thinner.
Precisely how HAART might weaken bones is unclear. One theory is that drugs such as protease inhibitors and non-nukes interfere with the liver's ability to process many substances and hormones, including vitamin D, which some researchers consider a hormone. The liver converts vitamin D to its active form so that it can help the body retain calcium.
In laboratory experiments with cells and protease inhibitors, these drugs impaired the conversion of vitamin D between 32% and 80%, depending on the drug tested. This effect of protease inhibitors may reduce the amount of activated or useful vitamin D available for the body. In turn, this reduction in activated vitamin D may decrease the body's ability to retain calcium and build strong bones. These findings need to be confirmed but they underscore the importance of a minimum daily intake of 400 international units of vitamin D per day.
Researchers in Western Australia have also been studying the impact of anti-HIV therapy on the bones of 171 male PHAs. The research team found that an astonishingly high proportion of subjects - nearly 50% - were losing significant amounts of calcium from their bones. As well, 17% of subjects had thinning bones. Both of these groups of subjects were using protease inhibitors.
The research team also found that loss of subcutaneous fat was linked to the development of weaker bones. Interestingly, they also observed that those people using indinavir were more likely to experience a thickening of their bones compared with the bones of people using nelfinavir-based regimens. This association between indinavir and bone thickness was even found in indinavir users who were losing subcutaneous fat.
The fact that thin bones may be linked to fat wasting is interesting because it raises the possibility that nukes, which have been associated with fat wasting, might play a role in the weakening of bones. Clearly, further investigation needs to be conducted on the impact of anti-HIV drugs on bone formation and destruction as well as on the hormones associated with bone development.
1. Tebas P, Yarasheski KE, Whyte M, et al. Serum and urine markers of bone mineral metabolism in HIV infected patients taking protease inhibitor containing potent antiretroviral therapy. Abstract 029.
2. Dusso A, Vidal M, Powderly WG, et al. Protease inhibitors inhibit in vitro conversion of 25(OH)-vitamin D to 1,25(OH)2-vitamin D. Abstract 030
3. Nolan D, Upton R, James I, et al. Longitudinal analysis of bone mineral density (BMD) in HIV-infected patients treated with HAART: changes in BMD correlate with change in subcutaneous fat; with an additional independent effect of indinavir therapy to increase BMD. Abstract 031.
4. Mallal SA, John M, Moore C, et al. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 2000;14(10):1309.
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