Dutch find low bone mineral density in gay men, regardless of HIV infection status

The prevalence of low bone mineral density (BMD) is similar in HIV-positive and HIV-negative gay men, according to the results of Dutch research published in the online edition of the Journal of Infectious Diseases. The only significant risk factor for reduced BMD was low body mass index (BMI).

“HIV infection was not associated with BMD,” write the authors, “part of the low BMD previously reported in HIV-infected MSM [men who have sex with men] pre-dates HIV-acquisition.”

Several studies have shown a higher prevalence of low BMD in HIV-positive people compared to age- and sex-matched individuals in the general population. The inflammation caused by HIV infection and the side-effects of some antiretroviral drugs are possible reasons for this finding.

However, Dutch investigators found a high prevalence of low BMD in HIV-positive gay men who had recently been infected with HIV. None of these men had any of the biological markers associated with increased bone turnover.

This led the researchers to postulate that the low BMD observed in these people pre-dated their infection with HIV.

They therefore designed a study, comparing bone mineral density in three groups of gay men: those with primary HIV infection (known infection within the previous six months); men with chronic HIV infection; and HIV-negative men. The authors also compared biochemical markers of bone formation between these three groups.

The study was conducted between 2008 and 2011. Bone density was assessed using dual energy X-ray (DEXA) scans.

 A total of 41 men with primary HIV infection, 106 individuals with chronic HIV infection and 30 HIV-negative controls were recruited to the study. All were aged between 20 and 55 years. None had risk factors for low BMD such as injecting drug use or kidney disease.

T- and Z-scores for bone density at the lumbar spine, femoral neck of the hip and total hip were calculated. Low BMD was defined as a Z-score of -2.0 the standard deviation (SD) for healthy age- and sex- matched controls.

The three study groups were well matched in terms of age and race. However, HIV-negative men were heavier (82 kg) than those with primary or chronic HIV infection (74 kg; p = 0.009). BMI also differed between the HIV-negative (24.4 kg/m²) and HIV-positive (22.7 kg/m²; p = 0.04) participants.

The prevalence of traditional risk factors for low BMD was slightly higher among the men with primary HIV infection compared to the HIV-negative men, but the differences were not significant.

However, some biomarkers of increased bone turnover did differ between these two groups. Serum phosphate and bone formation marker P1NP were significantly lower in those with primary HIV infection compared to the controls (p < 0.001 and p = 0.009 respectively). The participants with primary HIV infection also had higher levels of alkaline phosphate (p = 0.04), sex hormone-binding globulin (p = 0.01) and the bone resorption marker CTX (p = 0.001) than the HIV-negative participants.

Regardless of these findings, the prevalence of low BMD at one or more anatomical sites did not differ significantly between the three groups, and was detected in 20% of participants with primary HIV, 22% of those with chronic HIV infection and 13% of the HIV-negative controls. The prevalence of low BMD in the control participants was similar to that observed in other research involving HIV-negative gay men.

“Two antiretroviral pre-exposure prophylaxis (PrEP) trials reported a 10-14% prevalence of low BMD…in healthy HIV-seronegative MSM who were at risk for HIV infection,” note the authors. “One of these studies observed that low BMD was associated with inhalants (i.e. poppers, amyl nitrates) and amphetamine use.”

With the exception of total hip Z-score in the HIV-negative controls, the lumbar spine, femoral neck and total hip T- and Z-scores in all three study groups were significantly less than zero, “indicating that the average bone density in our study populations was lower than the average bone density of the…reference population”.

Lumbar spine BMD and T- and Z-scores were slightly, but not significantly, lower in the men with HIV compared to the HIV-uninfected controls.

Femoral neck and total hip BMD, T- and Z-scores did not differ between the HIV-infected men and the HIV-negative individuals.

Statistical analysis failed to find any evidence that the men with HIV had an increased risk of bone mineral density compared to the control population. Low BMI was, however, a significant risk factor (p = 0.001 to p < 0.001).

How can these findings be explained?

The authors suggest that it could be because gay men are more likely than heterosexual men to have “lifestyle factors for low BMD such as low body weight, smoking, alcohol and recreational drug use”. They believe this is an important consideration when designing studies to assess the impact of HIV infection and its treatment on BMD. “To precisely measure the effect of HIV-infection on BMD in MSM, it is important to use adequate control groups comprising HIV-negative MSM.”

Grijsen ML et al. Low bone mineral density in men who have sex with men regardless of HIV status. J Infect Dis, online edition, 2012.