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A placebo-controlled study of alendronate in HIV-positive people

Researchers in France conducted a randomized, placebo-controlled study called ANRS 120-Fosivir in HIV-positive people with osteoporosis. The two-year study of alendronate revealed that the drug was safe and significantly improves bone mineral density.

Study details

Researchers screened more than 1,000 potential volunteers who had been HIV positive for at least five years to find participants with osteoporosis who did not have additional complications or conditions that could have had an impact on the study, such as the following:

  • alcoholism
  • difficulty swallowing medication
  • stomach ulcers
  • recent history of cancer
  • vitamin D deficiency
  • hormonal disorders (including those affecting thyroid and sex hormones)
  • being underweight
  • having previously received testosterone therapy
  • serious heart, liver or kidney disease
  • recent use of corticosteroids
  • ongoing infections (apart from HIV)
  • women who were breast-feeding or pregnant or planning to become pregnant
  • received previous treatment for osteoporosis

After screening 1,079 people (842 men, 237 women), researchers randomly assigned 44 participants to one of the following interventions:

  • alendronate (20 people) – 70 mg once weekly (taken orally)
  • placebo (24 people) – once weekly (taken orally)

All participants also took 500 mg of calcium carbonate and 400 IU of vitamin D daily.

Low-dose X-ray scans (DEXA) were used to assess bone mineral density.

The average profile of the 44 participants at the start of the study was as follows:

  • 42 males, 2 females
  • age – 45 years
  • 40% had a history of AIDS
  • CD4+ cell count – 422 cells
  • viral load – less than 50 copies
  • all participants had osteoporosis
  • 32% were taking tenofovir (evenly distributed between alendronate and placebo users)
  • 40% were smokers

The study lasted for two years.

Results

At the end of the second year of the study, participants taking alendronate had significantly improved bone mineral density compared to participants who took placebo. Overall, bone mineral density increased at the spine or hip by 7% among alendronate users compared to placebo (1%). This difference was statistically significant.

Changes in bone mineral density at specific parts of the body were distributed as follows:

Spine

  • alendronate: +7%
  • placebo: +1%

Hip

  • alendronate: +4%
  • placebo: + 2%

The changes in bone mineral density of the hip were not statistically significant, likely because the changes were small; in order to detect a meaningful and statistically significant change, more participants would have been needed.

Adverse effects

Levels of liver enzymes in the blood were normal in all participants. There were no obvious differences in side effects between drug and placebo. This is not surprising, as alendronate is generally well tolerated when taken exactly as directed.

Fractures

Two fractures occurred among placebo users and none among alendronate users.

Gender imbalance

As with many HIV-related studies in high-income countries, the present study was imbalanced with respect to gender. Researchers explained this problem by noting that they did not recruit postmenopausal women because they wanted to “rule out an effect of osteoporosis risk factors [other] than HIV infection and its treatment.” They also noted that osteoporosis seemed “less frequent in women than men in the HIV-infected population [in France].” The results in the study’s two women were similar to that of men.

The present study has a robust design and produced clear results, confirming the beneficial effect of alendronate in HIV-positive men who have osteoporosis.

The long-term (between 10 and 15 years) use of alendronate has only been studied in elderly HIV-negative women. As alendronate and similar drugs are likely to be used in young and middle-aged HIV-positive people, long-term studies are needed to assess the drug’s safety and effectiveness in this population, particularly in HIV-positive women.

— Sean R. Hosein

REFERENCE:

Rozenberg S, Lanoy E, Bentata M, et al. Effect of alendronate on HIV-associated osteoporosis: A randomized, double-blind, placebo-controlled, 96-week trial (ANRS 120). AIDS Research & Human Retroviruses. 2012; in press.