HIV Patients Suffer More Fractures

Jim Kling

March 11, 2011

March 11, 2011 — Individuals with HIV infections have higher rates of bone fractures than the general US population, according to a study published online March 11 and in the April 15 issue of Clinical Infectious Diseases.

Studies suggest that low bone mineral density is a common adverse effect of antiretroviral therapy. A recent meta-analysis suggests that low bone mineral density is present in 67% of HIV-infected individuals. The same study concluded that 15% of those individuals suffered from osteoporosis. Only a few studies have examined the rate of bone fractures among persons infected with HIV.

To assess whether HIV-positive patients are at greater risk for bone fractures, Benjamin Young, MD, PhD, from the Rocky Mountain CARES/Denver Infectious Disease Consultants, Colorado, and colleagues analyzed data from the HIV Outpatient Study (HOPS), which is an open prospective cohort study of HIV-infected adults. Follow-up was conducted at 10 HIV clinics in the United States between 2000 and 2008. The researchers noted the rates of first fractures at any anatomic site.

Fracture rates were indirectly standardized to the general population by age and sex, based on data from the National Hospital Ambulatory Medical Care Survey (NHAMCSOPD). Cox proportional hazards modeling was used to assess factors associated with fractures.

Of the 5826 active HOPS patients included (median baseline age, 40 years; men, 79%; white, 52%; exposure to antiretroviral therapy, 73%), incident fractures occurred in 233 patients (crude annual rates, 59.6 - 93.5 fractures per 10,000 persons). There was an increase in age-standardized fracture rates from 2000 to 2002 (57.7 [95% confidence interval (CI), 41.6 - 108.0] to 84.8 [95% CI, 68.1 - 146.1]; P = .01), followed by stabilization. In contrast, the rate in NHAMCSOPD in 2000 was 29.1 (95% CI, 10.1 - 44.1), and in 2006 it was 35.9 (95% CI, 24.1 - 53.5).

In patients between 25 and 54 years of age, fracture rates and relative proportion of fragility fractures (defined as occurring at the wrist, vertebra, and femoral neck of the hip) were higher among HOPS patients than in NHAMCSOPD patients. Factors associated with incident fractures included older age, substance abuse, nadir CD4+ cell count lower than 200 cells/mm3 (adjusted hazard ratio [aHR], 1.60; 95% CI, 1.11 - 2.31), hepatitis C infection (aHR, 1.61; 95% CI, 1.13 - 2.29), and diabetes (aHR, 1.62; 95% CI, 1.00 - 2.64)

Among HOPS patients, factors independently associated with fragility fractures included greater age, hepatitis C virus coinfection, and body mass index lower than 18.5 kg/m2.

The authors believe that the study is the first to show an association between low nadir CD4+ cell count and fracture rates. The mechanism for such an association is unclear and should be the subject of further study, according to the authors. "It has recently been proposed that immune recovery itself may intrinsically offset the balance between osteoclast and osteoblast activity," which could cause a reduction in bone mineral density, Paul E. Sax, MD, clinical director of the HIV Program at Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.

There is no current consensus for the clinical management of bone health in HIV-infected individuals. The European AIDS Clinical Society recommends screening HIV-infected adults for fracture risk at age 40 years and older, whereas other recommendations suggest screening at age 50 years and older.

The results suggest that younger HIV-infected adults are at significant risk for fractures and should also be considered for screening. "I'm going to be a little more in tune to my [HIV-infected] patients' bone density at a younger age, making sure they're getting adequate calcium and vitamin D in their diet. They might be candidates for bisphosphonate therapy to decrease bone density loss," said Michael Archdeacon, MD, professor of orthopedic surgery at the University of Cincinnati College of Medicine in Ohio, in an interview with Medscape Medical News.

The study was supported by the Centers for Disease Control and Prevention. One of the authors has received research support from Cerner, Gilead Sciences, Merck, and GlaxoSmithKline and is a member of advisory boards or speaker's bureaus for GlaxoSmithKline, Merck, and ViiV Healthcare. Dr. Sax has been a consultant for Abbott, Bristol-Myers Squibb, Gilead, Glaxo-Smith Kline, Merck, Tibotec, and ViiV and has received grant support from Gilead, Merck, Tibotec, and ViiV. Dr. Archdeacon has disclosed no relevant financial relationships.

Clin Infect Dis. 2011;52:1061-1068.