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AIDS 2012: HIV+ Men Prone to Bone Fractures at Earlier Age

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HIV positive men in the long-running MACS cohort appeared to sustain osteoporosis-related bone fractures at an earlier age than HIV negative men, researchers reported at the recent XIX International AIDS Conference (AIDS 2012) in Washington, DC. A related study found several factors that predict greater risk of fractures, including use of protease inhibitors and proton pump inhibitors.

Several studies have shown that people with HIV are at greater risk for bone loss, but it is not clear whether this is due to HIV infection itself, resulting inflammation or metabolic abnormalities, toxicities of antiretroviral drugs, or a combination of factors. However, the relationship between bone loss and fractures in this population is not well understood.

Vanessa Walker Harris from Johns Hopkins University School of Medicineand colleagues assessed whether incidence of osteoporosis-related fracture increased in HIV positive compared with HIV negative men, as well as how fracture risk changes with age.

The researchers looked at incident (new) bone fractures among more than 5000 men living with or at risk for HIV infection in the Multicenter AIDS Cohort Study (MACS) between 1996 and 2011. They used the FRAX definition of fractures of the hip, humerus (upper arm), forearm, or spine.

All participants were over 30 years of age, with an average of approximately 46 years; about 75% were white. The mean body mass index (BMI) was about 26 (considered overweight), about one-quarter were current smokers, and nearly 45% were former smokers -- both risk factors for bone loss.

Results

  • Among 5106 men in the cohort, a total of 103 FRAX-defined fractures were reported:

o   53 in the HIV positive group, or 0.15 per 100 person-years;

o   50 in the HIV negative group, or 0.13 per 100 person-years.

  • HIV positive men had a 38% higher fracture risk (adjusted relative risk [RR] 1.38), but this did not reach statistical significance.
  • Fracture rates rose with age, after adjusting for BMI and race:

o   30-49 years: 0.12 per 100 person-years;

o   50-64 years: 0.15 per 100 person-years;

o   Over 65 years: 0.36 per 100 person-years.

  • The 50-64 age group had a non-significant 19% higher risk than the youngest group (adjusted RR 1.19), while the oldest group had nearly triple the risk (adjusted RR 2.93).
  • The interaction of HIV status and age did not reach statistical significance.

"HIV-infected men in the MACS have increased rates of fractures, particularly as they age," the researchers concluded. "These data provide support for recommendations for osteoporosis screening in HIV-infected men between the ages of 50 and 70."

Severity of Illness

Julie Womack from Yale School of Nursing and fellow investigators with the Veterans Aging Cohort Study Project Team looked at the association between overall severity of illness and risk of fragility fractures of the hip, vertebra, or upper arm among 40,115 men in the VACS cohort between 1997 and 2009.

The average age at baseline was 46 years and the average at the time of fracture was 53 years; just over one-third were white. The median CD4 T-cell count at baseline was 280 cells/mm3, 27% were HCV coinfected, and the median BMI was 25. Three-quarters were either current or past smokers and 16% had an "alcohol-related diagnosis." Follow-up time averaged 6 years.

In addition, 64% had used an HIV protease inhibitor, 41% had used tenofovir (Viread, also in the Truvada, Atripla, and Complera combinations), and 36% had used a proton pump inhibitor to reduce gastric acid production -- all drugs associated with bone loss.

The researchers used the VACS Index to assess severity of illness, a composite score based on routine clinical data including age, CD4 cell count, HIV viral load, hemoglobin level, ALT and AST liver enzyme levels, platelet level, creatinine, and hepatitis C status; higher scores indicate greater disease severity. The median VACS Index score at baselines was 33.

Results

  • A total of 588 fragility fractures were observed during follow-up, for anunadjusted fracture incidence rate of 0.25 per 100 person-years.
  • Factors significantly associated with increased fracture risk included:

o   VACS Index score: hazard ratio [HR] 1.08;

o   Higher BMI: HR 0.88;

o   Current protease inhibitor use: HR 1.28.

o   Alcohol-related diagnosis: HR 1.58;

o   Current proton pump inhibitor: HR 1.81;

o   Cerebrovascular disease or stroke: HR 1.87;

o   White race: HR 1.94.

"Higher VACS Index scores were associated with greater risk of fracture in this population of HIV+ male veterans," the researchers concluded. "This relationships appears to be driven primarily by age and hemoglobin."

"Current proton pump inhibitor use and protease inhibitor use were independently associated with fracture risk," they continued. However, "[s]teroid use and smoking were not statistically significantly associated with fracture risk" in this analysis, and they suggested that "[c]ontrolling for BMI, alcohol use, and disease severity may account for the weak associations."

"The only HIV-specific variable associated with fracture was current protease inhibitor use," they noted. "As we accounted for disease severity in the model, it is likely that protease inhibitor use influences fractures through a different mechanism."

8/21/12

References

V Walker Harris, K Althoff, S Reynolds, et al. Incident bone fracture in men with, or at risk for, HIV-infection in the Multicenter AIDS Cohort Study (MACS), 1996-2011. XIX International AIDS Conference (AIDS 2012).  Washington, DC, July 22-27, 2012. Poster MOPE086.

J Womack, J Goulet, C Gibert, et al (Veterans Aging Cohort Study Project Team). Severity of illness and fracture risk (Proton pump inhibitor and protease inhibitor use are associated with fragility fracture risk in HIV-positive male veterans). XIX International AIDS Conference (AIDS 2012).  Washington, DC, July 22-27, 2012.Poster MOPE087.