Bob Roehr

October 28, 2008

October 28, 2008 (Washington, DC) – A pair of studies are an offering explanation for the loss in bone mineral density (BMD) that many HIV-infected patients experience and suggesting possible interventions to reverse the process. The 2 posters were presented here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

Nested within the SMART study, which compared continuous and interrupted antiretroviral therapy, was a body-composition substudy, which used quantitative computer tomography and dual-energy x-ray absorptiometry to measure lumbar spine and total hip BMD. Data from 214 participants with baseline and annual follow-up examinations were compared with those from healthy young (20 to 30 years) aged-matched pairs, as was change from baseline for each individual.

Lead author Birgit Grund, PhD, said the use of antiretroviral therapy accelerated the normal BMD loss seen in aging, and that continuous use was associated with greater loss and increased risk for fracture. Dr. Grund is a statistician at the University of Minnesota, in Minneapolis.

She told Medscape HIV/AIDS that some patients began supplementation in the hope of stemming or reversing this process, "but the number was too small to reach any conclusions."

Calvin Cohen, MD, a clinician from the Community Research Initiative of New England, in Boston, Massachusetts, noted that the SMART substudy "showed no consistency with drugs associated with BMD loss." This finding is contrary to what some other studies have seen, particularly with regard to tenofovir: "We don't see a consistent statement that tenofovir is any different from any other nucleoside analogue."

However, he acknowledged the possibility that supplementation might have affected comparisons within the relatively small subsets of use of individual drugs. "I would say that this is the beginning of a question mark. It seems too premature to begin connecting the dots."

On the flip side of the poster stand was a study by Kathryn Childs, MD, which suggested there is a link between the use of tenofovir (TDF) and a shift in secondary hyperparathyroidism that is indicative of abnormal calcium metabolism, which can result in osteopenia and osteoporosis.

Primary components of the study of 51 men on antiretroviral therapy, conducted at Mount Sinai School of Medicine in New York City, were blood-level measures of 25-hydroxyvitamin (OH)D, the active form of vitamin D, and parathyroid hormone (PTH).

The study found that 39% of patients taking TDF/emtricitabine (FTC) had suboptimal 25(OH)D levels and PTH levels above the upper limits of normal. The condition was not seen in patients with sufficient levels of vitamin D. Multivariable analysis showed that 25(OH)D levels and TDF/FTC use were independently associated with elevated plasma concentrations of PTH (P = .03 and P = .4, respectively).

"We recommend that patients on tenofovir have vitamin D and PTH levels checked. And we hypothesize that vitamin D and calcium supplements will probably mitigate this effect." Dr. Childs told Medscape HIV/AIDS. She said there is a need for clinical trials to confirm this and to identify the appropriate levels of supplementation.

"I think it is an important observation," conference cochair and Columbia University researcher Scott Hammer, MD, told Medscape HIV/AIDS. Given that HIV has become a chronic, manageable disease, "we now have to think very broadly about the standard, routine issues, many of which are associated with aging."

He noted the growing body of literature associating vitamin D deficiency with increased risk for many cancers, elevated lipid levels, and cardiovascular disease.

Dr. Hammer believes that physicians should routinelytest for serum vitamin D levels as a standard part of care. This is particularly true in the winter months and in situations when patients may not be getting significant sun exposure. Darker-skinned people are at a higher risk for vitamin D insufficiency at all times because of the way their skin processes vitamin D. He is integrating wellness activities such as this into his practice.

The studies were conducted with university and NIH support. None of the researchers or commentators have disclosed any relevant financial relationships.

48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstracts H-2312a, H-2300. Presented October 27, 2008.

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