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People with HIV Have Increased Bone Fracture Risk

HIV positive people in the HIV Outpatient Study were more likely to sustain bone fractures compared with the general population of the same age, according to a study described in the March 10, 2011, advance online edition of Clinical Infectious Diseases. In addition to known factors including hepatitis C coinfection, lowest-ever CD4 cell count was identified as a new risk factor for bone breaks.alt

A growing body of evidence indicates that people with HIV are at risk for osteoporosis, or loss of bone mineral density, although it is not yet fully understood whether this is due to HIV infection itself, resulting inflammation, antiretroviral drugs, or some combination of these and other factors.

Studies often look at changes in bone density as revealed by DEXA scans. Data may be described in terms of T-scores and Z-scores, which compare an individual's bone mineral density against population norms for people of the same age and sex. But the clinical relevance of such changes is not clear, and there have been few studies of clinical outcomes such as fractures among HIV positive people.

To better understand this issue, Benjamin Young and fellow investigators with the HIV Outpatient Study (HOPS) analyzed first fractures at any anatomical site among cohort participants during 2000-2008. They then compared fracture rates in the cohort against those of the general population matched for age and sex, using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS).

HOPS is a prospective cohort study of HIV positive adults followed at 10 HIV clinics in 8 U.S. cities. Among the 5826 active HOPS participants analyzed for this study, 79% were men, 52% were white, and the median age at baseline was 40 years. About three-quarters had used antiretroviral therapy (ART).


  • A total of 233 patients, or 73%, sustained new fractures during a median follow-up period of 3.8 years, yielding crude annual rates of 59.6-93.5 fractures per 10,000 persons.
  • Age-matched fracture rates increased from 2000 through 2002 -- from 57.7 to 84.8 per 10,000 persons -- but then stabilized.
  • Among people age 25-54, overall fracture rates were higher among HOPS participants than among NHAMCS participants, ranging from 1.98 to 3.69 times higher.
  • People with HIV also had a higher proportion of fragility fractures, or breaks due to bone weakness rather than trauma:

o HIV positive men had significantly more vertebra (spine) and wrist fractures;

o HIV positive women sustained more vertebra and femoral neck (hip) fractures.

  • However, men and women in HOPS experienced relatively fewer non-fragility fractures compared with NHAMCS participants.
  • In a multivariate analysis, significant risk factors for new fractures included:
    • Older age (> 47 years);
    • Substance abuse;
    • Hepatitis C coinfection (adjusted hazard ratio [aHR] 1.61);
    • Diabetes (aHR 1.62);
    • Nadir or lowest-ever CD4 T-cell count < 200 cells/mm3 (aHR 1.60).
  • Risk factors for fragility fractures included:
    • Older age (aHR 1.43 per additional 10 years);
    • Hepatitis C coinfection (aHR 1.99, or about double the risk);
    • Low body mass index < 18.5 (aHR 3.72, or nearly 4 times higher risk).
Based on these findings, the researchers concluded, "Age-adjusted fracture rates among HOPS patients were higher than rates in the general U.S. population during the period 2000-2006."

"Clinicians should regularly assess HIV-infected persons for fracture risk, especially those with low nadir CD4 cell counts or other established risk factors for fracture," they recommended.

"We believe that our analysis is the first to highlight a possible association of low nadir CD4 cell count with incident fracture rates," they stated in their discussion. "The causal mechanism by which low nadir CD4 cell count is associated with low [bone mineral density] and fracture risk is unclear and warrants further investigation."

"The optimal clinical management of bone health in HIV-infected individuals is not well defined and remains controversial," Young said in a press release issued by the Infectious Diseases Society of America, which publishes Clinical Infectious Diseases.

"We believe our data support the need to develop guidelines that address screening for and correcting reversible causes of low bone mineral density and fall risk and that these activities should be incorporated into the routine care of HIV-infected patients," he added.

This past fall an international team of HIV experts reviewed recent research on bone problems in people with HIV and developed a set of recommendations. All HIV positive women who have reached menopause and HIV positive men age 50 or older should undergo DEXA bone density screening, they advised. To prevent bone problems, patients should take calcium and vitamin D supplements, get adequate sun exposure, and exercise regularly.

Noting that their findings suggest that younger HIV positive adults are also at significant risk for fragility fractures, Young and colleagues recommended that they too "should be considered for similar screening interventions."

Investigator affiliations: Rocky Mountain Center for AIDS Research, Education, and Services/DIDC, Denver, CO; Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA; Cerner, Vienna, VA; Health Connections International, Amsterdam, Netherlands.

< B Young, CN Dao, K Buchacz, et al (HIV Outpatient Study Investigators). Increased Rates of Bone Fracture among HIV-infected Persons in the HIV Outpatient Study (HOPS) Compared with the US General Population, 2000-2006. Clinical Infectious Diseases (free full text) March 10, 2011 (Epub ahead of print).

Other Source

Infectious Diseases Society of America. Research suggests HIV-infected patients at higher risk for bone fractures. Press release. March 11, 2011.