Low bone mineral density in Botswana PrEP trial participants raises concerns

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Researchers conducting a trial of tenofovir and FTC as pre-exposure prophylaxis (PrEP) in Botswana have found low bone mineral density (BMD) levels in HIV-negative volunteers at enrolment. The finding raises concerns about further bone mineral loss, found in some studies to be associated with tenofovir use.

However researcher Lynn Paxton, noting that the ‘normal’ levels against which the findings were calibrated were taken from those in young American adults, said that these levels might simply be invalid for African populations.

“We have very little information on BMD in young healthy African populations,” she said.

Glossary

bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 

osteopenia

A condition in which bone mineral density is lower than normal, but less severe than osteoporosis.

osteoporosis

Bone disease characterised by a decrease in bone mineral density and bone mass, resulting in an increased risk of fracture (a broken bone).

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.

hormone

A chemical messenger which stimulates or suppresses cell and tissue activity. Hormones control most bodily functions, from simple basic needs like hunger to complex systems like reproduction, and even the emotions and mood.

The PrEP study was launched in 2007 in Gaborone and Francistown in Botswana. Bone mineral density measures were only taken from participants in Gaborone. The trial is a phase III trial of tenofovir plus FTC as PrEP in adults aged 18 to 39 who have had sex in the previous twelve months. All trial participants must have normal liver and renal function, but normal levels for bone mineral density had not yet been set.

Researchers accordingly used Dual Emission X-Ray Absorptiometry (DEXA) to measure baseline wrist, hip and lumbar spine (L-spine) BMD in a subset of 216 Batswana study participants, 114 women and 102 men, aged 20 to 29 (mean age 24). DEXA results for more than half of study participants indicated low bone mineral density in at least one of the three body regions.

Using US National Institutes of Health Division of AIDS definitions for osteopenia (a T-score ranging from -1 to -2.5) and osteoporosis (a T-score lower than -2.5), researchers classified most cases of low BMD as the less severe osteopenia. A T-score of minus one means that their bone mineral density lies in the bottom one-sixth of the population while a T score of minus 2.5 means that they are in the bottom 0.62% of the population.

Osteopenia of the wrist and lumbar spine was common. Twenty-two per cent of women and 50% of men had osteopenia in the wrist, and 39 and 40% respectively in the lumbar spine. Hip osteopenia was less common, at 9% in women and 5% in men. Osteoporosis was rarer. Four men had osteoporosis in the wrist and one in the lumbar spine while one woman had lumbar spine osteoporosis. All trial volunteers found to have osteopenia were given calcium supplements.

There was a strong correlation between low body weight and low BMD in the wrist and hip but not in the spine. Underweight study participants (BMI less than 18.5, n = 39) had the highest rates of wrist and hip osteopenia (48.7 and 15.4%, respectively, compared with 35.5 and 6.5% for those of normal body weight and 20.5% and zero in the overweight (BMI more than 25, n = 39). However there was no such correlation in spinal BMD; the L-spine osteopenia rate of 25.6% in people with low BMD was considerably lower than the 47.8% rate found in participants with normal BMI.

Two of the low-BMI and two of the average-BMI participants had wrist osteoporosis and one each had spinal osteoporosis. In a multivariate analysis, the only independent predictor of low BMD was male sex. Fifteen per cent of the women were taking hormonal contraception, which can change BMD levels, but there was no correlation with hormonal contraceptive use.

Paxton warned that this was a small study from a single geographical site. In speculating why “young, strapping African men” might have such low BMD, she said the local diet, which was heavy in starch, might contribute, as might observed high levels of alcohol use (62% of participants had used alcohol recently). However, since normal values were derived from American youth, they might also simply be using invalid normal values for an African population.

On the basis of their findings, she called for more studies of BMD prevalence in HIV-negative and HIV-positive Africans, including studies assessing nutritional status and alcohol use.

Further information

A powerpoint presentation by Lynn Paxton and a webcast of the conference session in which it was presented are available on the IAS 2009 website.